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  • 151.
    Rönnelid, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Hansson, Monika
    Mathsson, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Thermo Fisher Sci, Uppsala, Sweden.
    Cornillet, Martin
    Reed, Evan
    Jakobsson, Per-Johan
    Alfredsson, Lars
    Holmdahl, Rikard
    Skriner, Karl
    Serre, Guy
    Lundberg, Karin
    Klareskog, Lars
    Anticitrullinated protein/peptide antibody multiplexing defines an extended group of ACPA-positive rheumatoid arthritis patients with distinct genetic and environmental determinants.2018Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, nr 2, s. 203-211Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: The second generation anticycliccitrullinated peptide (anti-CCP2) assay detects the majority but not all anticitrullinated protein/peptide antibodies (ACPA). Anti-CCP2-positive rheumatoid arthritis (RA) is associated with HLA-DRB1* shared epitope (SE) alleles and smoking. Using a multiplex assay to detect multiple specific ACPA, we have investigated the fine specificity of individual ACPA responses and the biological impact of additional ACPA reactivity among anti-CCP2-negative patients.

    METHODS: We investigated 2825 patients with RA and 551 healthy controls with full data on anti-CCP2, HLA-DRB1* alleles and smoking history concerning reactivity against 16 citrullinated peptides and arginine control peptides with a multiplex array.

    RESULTS: The prevalence of the 16 ACPA specificities ranged from 9% to 58%. When reactivity to arginine peptides was subtracted, the mean diagnostic sensitivity increased by 3.2% with maintained 98% specificity. Of the anti-CCP2-negative patients, 16% were found to be ACPA positive. All ACPA specificities associated with SE, and all but one with smoking. Correction for arginine reactivity also conveyed a stronger association with SE for 13/16 peptides. Importantly, when all ACPA specificities were analysed together, SE and smoking associated with RA in synergy among ACPA positive, but not among ACPA-negative subjects also in the anti-CCP2-negative subset.

    CONCLUSIONS: Multiplexing detects an enlarged group of ACPA-positive but anti-CCP2-negative patients with genetic and environmental attributes previously assigned to anti-CCP2-positive patients. The individual correction for arginine peptide reactivity confers both higher diagnostic sensitivity and stronger association to SE than gross ACPA measurement.

  • 152.
    Rönnelid, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Tejde, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Mathsson, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Nilsson Ekdahl, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Nilsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Immune complexes from SLE sera induce IL10 productionfrom normal peripheral blood mononuclear cells by anFcvicious cycle maintaining B cell hyperactivity in SLEgRII dependent mechanism: implications for a possible vicious cycle maintaining B cell hyperactivity in SLE2003Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 62, nr 1, s. 37-42Artikkel, forskningsoversikt (Annet vitenskapelig)
    Abstract [en]

    BACKGROUND: Raised interleukin (IL)6 and IL10 levels are thought to contribute to the pathogenesis of systemic lupus erythematosus (SLE) by enhancing autoantibody production and immune complex (IC) formation. These immune complexes can then stimulate cellular reactions through Fc and complement receptors. OBJECTIVE: To investigate whether circulating SLE ICs stimulate type 2 cytokine production. METHODS: Twenty serum samples from patients with active SLE were compared with sera from 18 healthy controls. Sera and polyethylene glycol (PEG) precipitates from sera were added to peripheral blood mononuclear cell (PBMC) cultures, and the production of IL10 and IL6 was investigated by enzyme linked immunospot assay (ELISPOT) and enzyme linked immunosorbent assay (ELISA). Fc gamma receptor (FcgammaR) antibodies were used in blocking experiments, and flow cytometry was used to assess the correlation between monocyte FcgammaR expression and IC-induced cytokine production. RESULTS: Ten per cent dilutions of the SLE sera induced a significantly increased number of IL10-producing cells in comparison with control sera (median, 11.75 v 1.25 spot forming cells/50 000 PBMC; p<0.0001). PEG precipitates from SLE sera also induced significantly increased levels of IL10 (p=0.016) and IL6 (p=0.042) in comparison with control PEG precipitates. IL10 production induced by SLE PEG precipitates or by artificial ICs could be blocked by anti-FcgammaRII antibodies, and the FcgammaRII expression on CD14+ monocytes correlated with the IC-induced production of IL10 and IL6. CONCLUSIONS: SLE sera stimulate IL10 and IL6 production from PBMC, and this effect is at least partly explained by precipitable ICs acting through FcgammaRII. This effect provides a possible mechanism for the enhanced production of IL10 in SLE, whereby B cell activation, antibody production, IC stimulated monocytes/macrophages, and type 2 cytokines create a vicious cycle that may help to maintain B cell hyperactivity in SLE.

  • 153. Saevarsdottir, S.
    et al.
    Kristjánsdóttir, Helga
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi, Medicinsk genetik.
    Gröndal, G.
    Vikingsdottir, T.
    Steinsson, K.
    Valdimarsson, H.
    Mannan-binding lectin and complement C4A in Icelandic multicase families with systemic lupus erythematosus2006Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 65, nr 11, s. 1462-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To determine whether low mannan-binding lectin (MBL) and C4A null alleles (C4AQ0) are associated with systemic lupus erythematosus (SLE) in multicase families with SLE.

    Methods: Low MBL level was determined by measuring serum levels and by genotyping for mutant structural (B/C/D, designated as 0) and promoter (LX) alleles (by real-time polymerase chain reaction). C4AQ0 was detected by protein electrophoresis and corroborated with haplotype and genotype analysis. In nine Icelandic families, 24 patients with SLE were compared with 83 first-degree and 23 second-degree relatives without SLE. Twenty four unrelated family members and a population group of 330 Icelanders served as controls.

    Results: Overall, the frequency of low MBL genotypes (0/0, LX/0 and wild-type/0) tended to be higher in patients with SLE than in their first-degree and second-degree relatives (p = 0.06), but the frequency was similar in the families and in the controls (p = 0.6). The frequency of C4AQ0 was, however, increased in patients and their relatives compared with that in the controls (p = 0.04). The combination of low MBL genotypes and C4AQ0 was found more often in the patients than in their relatives (p = 0.03) and controls (p = 0.02). However, low MBL level was observed only in patients and first-degree relatives in five of the nine multicase families. In these five families, patients with SLE had low MBL genotypes more often (64%) than their first-degree (38%) and second-degree (0%) relatives (p = 0.001), and the patients with SLE also had, accordingly, lower MBL levels than their relatives (p = 0.001).

    Conclusions: These findings indicate that low MBL levels can predispose people to SLE and highlight the genetic heterogeneity of this disease.

  • 154.
    Saevarsdottir, Saedis
    et al.
    deCODE Genet Amgen, Reykjavik, Iceland.;Karolinska Inst, Dept Med, Div Clin Epidemiol, Stockholm, Sweden.;Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland.;Natl Univ Hosp Iceland, Dept Med, Landspitali, Reykjavik, Iceland..
    Stefansdottir, Lilja
    deCODE Genet Amgen, Reykjavik, Iceland..
    Sulem, Patrick
    deCODE Genet Amgen, Reykjavik, Iceland..
    Thorleifsson, Gudmar
    deCODE Genet Amgen, Reykjavik, Iceland..
    Ferkingstad, Egil
    deCODE Genet Amgen, Reykjavik, Iceland..
    Rutsdottir, Gudrun
    deCODE Genet Amgen, Reykjavik, Iceland..
    Glintborg, Bente
    Copenhagen Univ Hosp, Rigshosp, Copenhagen Ctr Arthrit Res COPECARE, Ctr Rheumatol & Spine Dis,Ctr Head & Orthopaed, Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Westerlind, Helga
    Karolinska Inst, Dept Med, Div Clin Epidemiol, Stockholm, Sweden..
    Grondal, Gerdur
    Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland.;Natl Univ Hosp Iceland, Dept Med, Landspitali, Reykjavik, Iceland.;Natl Univ Hosp Iceland, Ctr Rheumatol Res, Landspitali, Reykjavik, Iceland..
    Loft, Isabella C.
    Zealand Univ Hosp, Dept Clin Immunol, Koge, Denmark..
    Sorensen, Signe Bek
    Univ Oslo, Dept Med Genet, Oslo, Norway..
    Lie, Benedicte A.
    Univ Oslo, Dept Med Genet, Oslo, Norway.;Oslo Univ Hosp, Oslo, Norway..
    Brink, Mikael
    Umeå Univ, Dept Publ Hlth & Clin Med, Rheumatol, Umeå, Sweden..
    Ärlestig, Lisbeth
    Umeå Univ, Dept Publ Hlth & Clin Med, Rheumatol, Umeå, Sweden..
    Arnthorsson, Asgeir Orn
    deCODE Genet Amgen, Reykjavik, Iceland..
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Banasik, Karina
    Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Fac Hlth & Med Sci, Copenhagen, Denmark..
    Bank, Steffen
    Univ Hosp Southern Denmark, IRS Ctr Sonderjylland, Mol Diagnost & Clin Res Unit, Aabenraa, Denmark..
    Bjorkman, Lena, I
    Univ Gothenburg, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden..
    Ellingsen, Torkell
    Univ Southern Denmark, Open Explorat Network, Odense, Denmark.;Odense Univ Hosp, Rheumatol Res Unit, Odense, Denmark.;Univ Southern Denmark, Odense, Denmark..
    Erikstrup, Christian
    Aarhus Univ Hosp, Dept Clin Immunol, Aarhus, Denmark..
    Frei, Oleksandr
    Univ Oslo, NORMENT Ctr, Inst Clin Med, Oslo, Norway.;Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway.;Univ Oslo, Ctr Bioinformat, Dept Informat, Oslo, Norway..
    Gjertsson, Inger
    Gothenburg Univ, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden..
    Gudbjartsson, Daniel F.
    deCODE Genet Amgen, Reykjavik, Iceland.;Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland..
    Gudjonsson, Sigurjon A.
    deCODE Genet Amgen, Reykjavik, Iceland..
    Halldorsson, Gisli H.
    deCODE Genet Amgen, Reykjavik, Iceland.;Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland..
    Hendricks, Oliver
    Univ Hosp Southern Denmark, Danish Hosp Rheumat Dis, Sonderborg, Denmark.;Univ Southern Denmark, Dept Reg Hlth Res, Odense, Denmark..
    Hillert, Jan
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Hogdall, Estrid
    Univ Copenhagen, Herlev Hosp, Dept Pathol, Copenhagen, Denmark..
    Jacobsen, Soren
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.;Rigshosp, Ctr Rheumatol & Spine Dis, Copenhagen Lupus & Vasculitis Clin, Copenhagen, Denmark..
    Jensen, Dorte Vendelbo
    Gentofte & Herlev Hosp, Ctr Rheumatol & Spine Dis, Dept Rheumatol, Ronne, Denmark..
    Jonsson, Helgi
    Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland.;Natl Univ Hosp Iceland, Dept Med, Landspitali, Reykjavik, Iceland..
    Kastbom, Alf
    Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden..
    Kockum, Ingrid
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Kristensen, Salome
    Aalborg Univ Hosp, Dept Rheumatol, Aalborg, Denmark.;Aalborg Univ, Dept Clin Med, Aalborg, Denmark..
    Kristjansdottir, Helga
    Natl Univ Hosp Iceland, Ctr Rheumatol Res, Landspitali, Reykjavik, Iceland..
    Larsen, Margit H.
    Copenhagen Univ Hosp, Rigshosp, Dept Clin Immunol, Copenhagen, Denmark..
    Linauskas, Asta
    Aalborg Univ, Dept Clin Med, Aalborg, Denmark.;North Denmark Reg Hosp, Dept Rheumatol, Hjorring, Denmark..
    Hauge, Ellen-Margrethe
    Aarhus Univ Hosp, Dept Rheumatol, Aarhus, Denmark.;Aarhus Univ, Dept Clin Med, Aarhus, Denmark..
    Loft, Anne G.
    Aarhus Univ Hosp, Dept Rheumatol, Aarhus, Denmark.;Aarhus Univ, Dept Clin Med, Aarhus, Denmark..
    Ludviksson, Bjorn R.
    Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland.;Natl Univ Hosp Iceland, Dept Immunol, Landspitali, Reykjavik, Iceland..
    Lund, Sigrun H.
    deCODE Genet Amgen, Reykjavik, Iceland..
    Markusson, Thorsteinn
    deCODE Genet Amgen, Reykjavik, Iceland.;Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland..
    Masson, Gisli
    deCODE Genet Amgen, Reykjavik, Iceland..
    Melsted, Pall
    deCODE Genet Amgen, Reykjavik, Iceland.;Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland..
    Moore, Kristjan H. S.
    deCODE Genet Amgen, Reykjavik, Iceland..
    Munk, Heidi
    Univ Southern Denmark, Open Explorat Network, Odense, Denmark.;Odense Univ Hosp, Rheumatol Res Unit, Odense, Denmark.;Univ Southern Denmark, Odense, Denmark..
    Nielsen, Kaspar R.
    Aalborg Univ Hosp, Dept Clin Immunol, Aalborg, Denmark..
    Norddahl, Gudmundur L.
    deCODE Genet Amgen, Reykjavik, Iceland..
    Oddsson, Asmundur
    deCODE Genet Amgen, Reykjavik, Iceland..
    Olafsdottir, Thorunn A.
    deCODE Genet Amgen, Reykjavik, Iceland.;Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland..
    Olason, Pall, I
    deCODE Genet Amgen, Reykjavik, Iceland..
    Olsson, Tomas
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Ostrowski, Sisse Rye
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.;Copenhagen Univ Hosp, Rigshosp, Dept Clin Immunol, Copenhagen, Denmark..
    Horslev-Petersen, Kim
    Univ Hosp Southern Denmark, Danish Hosp Rheumat Dis, Sonderborg, Denmark..
    Rognvaldsson, Solvi
    deCODE Genet Amgen, Reykjavik, Iceland..
    Sanner, Helga
    Oslo Univ Hosp, Sect Rheumatol, Oslo, Norway.;Oslo New Univ Coll, Oslo, Norway..
    Silberberg, Gilad N.
    Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden..
    Stefansson, Hreinn
    deCODE Genet Amgen, Reykjavik, Iceland..
    Sorensen, Erik
    Copenhagen Univ Hosp, Rigshosp, Dept Clin Immunol, Copenhagen, Denmark..
    Sorensen, Inge J.
    Rigshosp, Ctr Rheumatol & Spine Dis, Copenhagen Lupus & Vasculitis Clin, Copenhagen, Denmark..
    Turesson, Carl
    Lund Univ, Dept Clin Sci, Rheumatol, Malmö, Sweden..
    Bergman, Thomas
    Karolinska Inst, Dept Med, Div Clin Epidemiol, Stockholm, Sweden..
    Alfredsson, Lars
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Kvien, Tore K.
    Univ Oslo, Oslo, Norway.;Diakonhjemmet Hosp, Oslo, Norway..
    Brunak, Soren
    Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Fac Hlth & Med Sci, Copenhagen, Denmark..
    Steinsson, Kristjan
    Natl Univ Hosp Iceland, Ctr Rheumatol Res, Landspitali, Reykjavik, Iceland..
    Andersen, Vibeke
    Univ Hosp Southern Denmark, IRS Ctr Sonderjylland, Mol Diagnost & Clin Res Unit, Aabenraa, Denmark.;Univ Southern Denmark, Open Explorat Network, Odense, Denmark.;Univ Southern Denmark, Inst Mol Med, Odense, Denmark..
    Andreassen, Ole A.
    Univ Oslo, NORMENT Ctr, Inst Clin Med, Oslo, Norway.;Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway..
    Rantapää-Dahlqvist, Solbritt
    Umeå Univ, Dept Publ Hlth & Clin Med, Rheumatol, Umeå, Sweden..
    Hetland, Merete Lund
    Copenhagen Univ Hosp, Rigshosp, Copenhagen Ctr Arthrit Res COPECARE, Ctr Rheumatol & Spine Dis,Ctr Head & Orthopaed, Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Klareskog, Lars
    Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden..
    Askling, Johan
    Karolinska Inst, Dept Med, Div Clin Epidemiol, Stockholm, Sweden..
    Padyukov, Leonid
    Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden..
    Pedersen, Ole Bv
    Zealand Univ Hosp, Dept Clin Immunol, Koge, Denmark..
    Thorsteinsdottir, Unnur
    deCODE Genet Amgen, Reykjavik, Iceland.;Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland..
    Jonsdottir, Ingileif
    deCODE Genet Amgen, Reykjavik, Iceland.;Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland.;Natl Univ Hosp Iceland, Dept Immunol, Landspitali, Reykjavik, Iceland..
    Stefansson, Kari
    deCODE Genet Amgen, Reykjavik, Iceland.;Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland..
    Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset2022Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 81, nr 8, s. 1085-1095Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.

    Fulltekst (pdf)
    FULLTEXT01
  • 155.
    Sandling, Johanna K.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Pucholt, Pascal
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Hultin-Rosenberg, Lina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Farias, Fabiana H. G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Washington Univ, Dept Psychiat, St Louis, MO 63110 USA..
    Kozyrev, Sergey V.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Alexsson, Andrei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Bianchi, Matteo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Padyukov, Leonid
    Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Bengtsson, Christine
    Umeå Univ, Dept Publ Hlth & Clin Med Rheumatol, Umeå, Sweden..
    Jonsson, Roland
    Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway..
    Omdal, Roald
    Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway.;Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Lie, Benedicte A.
    Univ Oslo, Dept Med Genet, Oslo, Norway..
    Massarenti, Laura
    Copenhagen Univ Hosp, Rigshosp, Ctr Rheumatol & Spine Dis, Inst Inflammat Res, Copenhagen, Denmark..
    Steffensen, Rudi
    Aalborg Univ, Dept Clin Immunol, Aalborg, Denmark..
    Jakobsen, Marianne A.
    Odense Univ Hosp, Dept Clin Immunol, Odense, Denmark..
    Lillevang, Soren T.
    Odense Univ Hosp, Dept Clin Immunol, Odense, Denmark..
    Lerang, Karoline
    Oslo Univ Hosp, Dept Rheumatol, Oslo, Norway..
    Molberg, Oyvind
    Oslo Univ Hosp, Dept Rheumatol, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Voss, Anne
    Odense Univ Hosp, Dept Rheumatol, Odense, Denmark..
    Troldborg, Anne
    Aarhus Univ Hosp, Dept Rheumatol, Aarhus, Denmark.;Aarhus Univ, Inst Clin Med, Aarhus, Denmark..
    Jacobsen, Soren
    Copenhagen Univ Hosp, Rigshosp, Ctr Rheumatol & Spine Dis, Copenhagen, Denmark.;Univ Copenhagen, Inst Clin Med, Copenhagen, Denmark..
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jonsen, Andreas
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Rheumatol, Lund, Sweden..
    Gunnarsson, Iva
    Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Svenungsson, Elisabet
    Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Rantapaa-Dahlqvist, Solbritt
    Umeå Univ, Dept Publ Hlth & Clin Med Rheumatol, Umeå, Sweden..
    Bengtsson, Anders A.
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Rheumatol, Lund, Sweden..
    Sjowall, Christopher
    Linköping Univ, Dept Biomed & Clin Sci, Div Inflammat & Infect, Linköping, Sweden..
    Leonard, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Lindblad-Toh, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Broad Inst MIT & Harvard, Cambridge, MA 02142 USA..
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Molecular pathways in patients with systemic lupus erythematosus revealed by gene-centred DNA sequencing2021Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 80, nr 1, s. 109-117Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease with extensive heterogeneity in disease presentation between patients, which is likely due to an underlying molecular diversity. Here, we aimed at elucidating the genetic aetiology of SLE from the immunity pathway level to the single variant level, and stratify patients with SLE into distinguishable molecular subgroups, which could inform treatment choices in SLE.

    METHODS: We undertook a pathway-centred approach, using sequencing of immunological pathway genes. Altogether 1832 candidate genes were analysed in 958 Swedish patients with SLE and 1026 healthy individuals. Aggregate and single variant association testing was performed, and we generated pathway polygenic risk scores (PRS).

    RESULTS: We identified two main independent pathways involved in SLE susceptibility: T lymphocyte differentiation and innate immunity, characterised by HLA and interferon, respectively. Pathway PRS defined pathways in individual patients, who on average were positive for seven pathways. We found that SLE organ damage was more pronounced in patients positive for the T or B cell receptor signalling pathways. Further, pathway PRS-based clustering allowed stratification of patients into four groups with different risk score profiles. Studying sets of genes with priors for involvement in SLE, we observed an aggregate common variant contribution to SLE at genes previously reported for monogenic SLE as well as at interferonopathy genes.

    CONCLUSIONS: Our results show that pathway risk scores have the potential to stratify patients with SLE beyond clinical manifestations into molecular subsets, which may have implications for clinical follow-up and therapy selection.

    Fulltekst (pdf)
    FULLTEXT01
  • 156. Snir, Omri
    et al.
    Widhe, Mona
    von Spee, Caroline
    Lindberg, Johan
    Padyukov, Leonid
    Lundberg, Karin
    Engström, Åke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Venables, Patrick J.
    Lundeberg, Joakim
    Holmdahl, Rikard
    Klareskog, Lars
    Malmström, Vivianne
    Multiple antibody reactivities to citrullinated antigens in sera from patients with rheumatoid arthritis: association with HLA-DRB1 alleles2009Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 68, nr 5, s. 736-743Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Autoantibodies to cyclic citrullinated peptides (anti-CCP) are present in most patients with rheumatoid arthritis (RA), and associate with HLA-DRB1 shared epitope (SE) alleles. Objective: To investigate reactivities of anti-CCP to various citrullinated proteins/peptides, which represent potential autoantigens in RA, and to examine the relationship between such antibodies, and their association with genetic variants within HLA-DRB1 SE alleles. Methods: Serum samples from 291 patients with established RA and 100 sex- and age-matched healthy subjects were included in this study. Sera were first analysed for presence of anti-CCP antibodies and further for IgG and IgA antibodies towards candidate autoantigens in both their native and citrullinated form including: fibrinogen, α-enolase peptide-1 and the C1-epitope of type II collagen (C1III). Antibody specificity was confirmed by cross-reactivity tests. HLA-DR genotyping was performed. Results: 72% of patients with RA were anti-CCP positive. Among the candidate autoantigens examined, IgG antibodies to citrullinated fibrinogen were found in 66% of patients' sera and in 41% for both citrullinated α-enolase peptide-1 and citrullinated C1III. These antibodies were mainly seen in the anti-CCP-positive patient group; they were specific for their respective antigen and displayed limited cross reactivity. IgA responses were also detected, but less frequently than IgG. Anti-CCP and anticitrullinated protein antibodies were associated with HLADRB1* 04 rather than with HLA-DRB1*01 alleles. Conclusions: Antibodies directed against several citrullinated antigens are present in CCP-positive RA, with many patients displaying multireactivity. All specific reactivities were primarily associated with the HLA-DRB1* 04 alleles, suggesting common pathways of anticitrulline immunity.

  • 157.
    Sohrabian, Azita
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Mathsson Alm, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Thermo Fisher Sci, ImmunoDiagnost Div, Uppsala, Sweden..
    Hansson, M.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Lysholm, J.
    Falun Cent Hosp, Clin Rheumatol, Falun, Sweden..
    Cornillet, M.
    Toulouse Univ, INSERM, U1056, Epithelial Differentiat & Rheumatoid Autoimmun, Toulouse, France..
    Knight, Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Skriner, K.
    Charite, Dept Med, Berlin, Germany..
    Serre, G.
    Toulouse Univ, INSERM, U1056, Epithelial Differentiat & Rheumatoid Autoimmun, Toulouse, France..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Weitoft, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Number Of Peptide-Specific Anti-Citrullinated Peptide Antibodies In Synovial Fluid And In Synovial Fluid Immune Complexes Associate With Degree Of Radiological Destruction And Response To Triamcinolone Hexacetonide For Knee Synovitis In Rheumatoid Arthritis2017Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 509-510Artikkel i tidsskrift (Annet vitenskapelig)
  • 158.
    Sohrabian, Azita
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Mathsson Alm, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Hansson, Monika
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Knight, Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Lysholm, Jörgen
    Falun Cent Hosp, Clin Rheumatol, Falun, Sweden.
    Cornillet, Martin
    Toulouse Univ, Lab Epithelial Differentiat & Rheumatoid Autoimmu, INSERM, U1056, Toulouse, France.
    Skriner, Karl
    Charite, Dept Med, Berlin, Germany.
    Serre, Guy
    Toulouse Univ, Lab Epithelial Differentiat & Rheumatoid Autoimmu, INSERM, U1056, Toulouse, France.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Weitoft, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Number of individual ACPA reactivities in synovial fluid immune complexes, but not serum anti-CCP2 levels, associate with inflammation and joint destruction in rheumatoid arthritis2018Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, nr 9, s. 1345-1353Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Individual patients with rheumatoid arthritis (RA) show divergent specific anti-citrullinated protein/peptide antibodies (ACPA) patterns, but hitherto no individual ACPA specificity has consistently been linked to RA pathogenesis. ACPA are also implicated in immune complexes (IC)-associated joint pathology, but until now, there has been no method to investigate the role of individual ACPA in RA IC formation and IC-associated pathogenesis.

    Methods: We have developed a new technique based on IC binding to C1q-coated magnetic beads to purify and solubilise circulating IC in sera and synovial fluids (SF) from 77 patients with RA. This was combined with measurement of 19 individual ACPA in serum, SF and in the IC fractions from serum and SF. We investigated whether occurrence of individual ACPA as well as number of ACPA in these compartments was related to clinical and laboratory measures of disease activity and inflammation.

    Results: The majority of individual ACPA reactivities were enriched in SF as compared with in serum, and levels of ACPA in IC were regulated independently of levels in serum and SF. No individual ACPA reactivity in any compartment showed a dominating association to clinical and laboratory measures of disease activity and severity. Instead, the number of individual ACPA reactivities in the IC fraction from SF associated with a number of markers of joint destruction and inflammation.

    Conclusions: Our data highlight the polyclonality of ACPA in joint IC and the possibility that a broad ACPA repertoire in synovial fluid IC might drive the local inflammatory and matrix-degrading processes in joints, in analogy with antibody-induced rodent arthritis models.

    Fulltekst (pdf)
    fulltext
  • 159.
    Sohrabian, Azita
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Parodis, I.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Carlströmer Berthen, N.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Sjowall, C.
    Linkoping Univ, Dept Clin & Expt Med, Rheumatol AIR, Linkoping, Sweden..
    Jonsen, A.
    Lund Univ, Sect Rheumatol, Dept Clin Sci Lund, Lund, Sweden..
    Zickert, A.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Frodlund, M.
    Linkoping Univ, Dept Clin & Expt Med, Rheumatol AIR, Linkoping, Sweden..
    Bengtsson, A.
    Lund Univ, Sect Rheumatol, Dept Clin Sci Lund, Lund, Sweden..
    Gunnarsson, I.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    High Anti-Dsdna Content in Sle Immune Complexes is associated with Clinical Remission Following Belimumab Treatment2017Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 861-862Artikkel i tidsskrift (Annet vitenskapelig)
  • 160. Sokka, T.
    et al.
    Kautiainen, H.
    Pincus, T.
    Toloza, S.
    Castelar Pinheiro, G. da Rocha
    Lazovskis, J.
    Hetland, M. L.
    Peets, T.
    Immonen, K.
    Maillefert, J. F.
    Drosos, A. A.
    Alten, R.
    Pohl, C.
    Rojkovich, B.
    Bresnihan, B.
    Minnock, P.
    Cazzato, M.
    Bombardieri, S.
    Rexhepi, S.
    Rexhepi, M.
    Andersone, D.
    Stropuviene, S.
    Huisman, M.
    Sierakowski, S.
    Karateev, D.
    Skakic, V.
    Naranjo, A.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Henrohn, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Farmakologi.
    Gogus, F.
    Badsha, H.
    Mofti, A.
    Taylor, P.
    McClinton, C.
    Yazici, Y.
    Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database2009Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 68, nr 11, s. 1666-1672Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To analyse associations between the clinical status of patients with rheumatoid arthritis ( RA) and the gross domestic product (GDP) of their resident country. Methods: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP'' countries with GDP per capita greater than US$ 24 000 and 11 "low GDP'' countries with GDP per capita less than US$ 11 000. Results: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP'' and "low GDP'' countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. Conclusions: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP'' than in "high GDP'' countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.

  • 161. Sokka, Tuulikki
    et al.
    Kautiainen, Hannu
    Toloza, Sergio
    Mäkinen, Heidi
    Verstappen, Suzan M.
    Lund Hetland, Merete
    Naranjo, Antonio
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Herborn, Gertraud
    Rau, Rolf
    Cazzato, Massimiliano
    Gossec, Laure
    Skakic, Vlado
    Gogus, Feride
    Sierakowski, Stanislaw
    Bresnihan, Barry
    Taylor, Peter
    McClinton, Catherine
    Pincus, Theodore
    QUEST-RA: quantitative clinical assessment of patients with rheumatoid arthritis seen in standard rheumatology care in 15 countries2007Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 66, nr 11, s. 1491-1496Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    To conduct a cross-sectional review of non-selected consecutive outpatients with rheumatoid arthritis (RA) as part of standard clinical care in 15 countries for an overview of the characteristics of patients with RA.

    METHODS:

    The review included current disease activity using data from clinical assessment and a patient self-report questionnaire, which was translated into each language. Data on demographic, disease and treatment-related variables were collected and analysed using descriptive statistics. Variation in disease activity on DAS28 (disease activity score on 28-joint count) within and between countries was graphically analysed. A median regression model was applied to analyse differences in disease activity between countries.

    RESULTS:

    Between January 2005 and October 2006, the QUEST-RA (Quantitative Patient Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis) project included 4363 patients from 48 sites in 15 countries; 78% were female, >90% Caucasian, mean age was 57 years and mean disease duration was 11.5 years. More than 80% of patients had been treated with methotrexate in all but three countries. Overall, patients had an active disease with a median DAS28 of 4.0, with a significant variation between countries (p<0.001). Among 42 sites with >50 patients included, low disease activity of DAS28 50% of patients had high disease activity of DAS28 >5.1.

    CONCLUSIONS:

    This international multicentre cross-sectional database provides an overview of clinical status and treatments of patients with RA in standard clinical care in 2005-6 including countries that are infrequently involved in clinical research projects.

  • 162.
    Spangeus, A.
    et al.
    Linkoping Univ Hosp, Linkoping, Sweden..
    Akesson, K.
    Lund Univ, Skane Univ Hosp, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Banefelt, J.
    Quantify Res, Stockholm, Sweden..
    Karlsson, L.
    Quantify Res, Stockholm, Sweden..
    Ortsater, G.
    Quantify Res, Stockholm, Sweden..
    Libanati, C.
    UCB Pharma, Brussels, Belgium..
    Toth, E.
    UCB Pharma, Brussels, Belgium..
    Strom, O.
    Quantify Res, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    The Treatment Gap After Fracture In Osteoporosis Patients In Sweden2017Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 72-72Artikkel i tidsskrift (Annet vitenskapelig)
  • 163. Stolt, Patrik
    et al.
    Yahya, Abqariyah
    Bengtsson, Camilla
    Källberg, Henrik
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Lundberg, Ingvar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Klareskog, Lars
    Alfredsson, Lars
    Silica exposure among male current smokers is associated with a high risk of developing ACPA-positive rheumatoid arthritis2010Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 69, nr 6, s. 1072-1076Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To study the association between silica exposure, separately as well as combined with smoking, and the risk of developing rheumatoid arthritis (RA) with or without the presence of antibodies against citrullinated peptide antigens (ACPA). Methods This Swedish population based case-control study analysed 577 incident RA cases and 659 randomly selected controls, all men aged 18-70 years, included during May 1996 to May 2006. Self-reported silica exposure, defined as exposure to stone dust, rock drilling or stone crushing and cigarette smoking was registered. ACPA status among cases was analysed. Results Silica-exposed subjects were found to have a moderately increased risk of ACPA-positive RA (odds ratio (OR) adjusted for age and residency = 1.67 (95% CI 1.13 to 2.48), but not of ACPA-negative RA (OR = 0.98 (95% CI 0.57 to 1.66)), compared with subjects unexposed to silica. Subjects exposed to rock drilling were found to have a somewhat more markedly increased risk of ACPA-positive RA (OR = 2.34 (95% CI 1.17 to 4.68)). A high risk of developing ACPA-positive RA was observed among silica-exposed current smokers (OR = 7.36 (95% CI 3.31 to 16.38)), exceeding the risk expected from the separate effects of silica exposure and current smoking, indicating an interaction between these exposures (attributable proportion due to interaction = 0.60 (95% CI 0.26 to 0.95)). Conclusion Silica exposure combined with smoking among men is associated with an increased risk of developing ACPA-positive RA. These results suggest that different inhalation exposures may interact in the aetiology of ACPA-positive RA.

  • 164.
    Sundbaum, J. K.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Lulea Univ Technol, Dept Hlth Sci, Lulea, Sweden.
    Ericsson, N.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Hallberg, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Lehto, N.
    Lulea Univ Technol, Dept Hlth Sci, Lulea, Sweden.
    Wadelius, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Methotrexate treatment in rheumatoid arthritis and elevated liver enzymes: a long-term follow-up of occurrence, predictors, surveillance, and outcome in clinical practice2018Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 977-977Artikkel i tidsskrift (Annet vitenskapelig)
  • 165. Svenungsson, Elisabet
    et al.
    Gustafsson, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Leonard, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sandling, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Gunnarsson, Iva
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jönsen, Andreas
    Bengtsson, Anders A
    Sturfelt, Gunnar
    Rantapää-Dahlqvist, Solbritt
    Elvin, Kerstin
    Sundin, Ulf
    Garnier, Sophie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Simard, Julia F
    Sigurdsson, Snaevar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Padyukov, Leonid
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti-phospholipid antibodies in systemic lupus erythematosus2010Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 69, nr 5, s. 834-840Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective

    To investigate whether the risk allele for systemic lupus erythematosus (SLE) in the signal transducer and activator of transcription factor 4 (STAT4) gene, defined by the single nucleotide polymorphism (SNP) rs10181656(G), is associated with vascular events and/or presence of prothrombotic anti-phospholipid antibodies (aPL) in patients with SLE.

    Methods

    Two independent groups of unrelated patients with SLE of Swedish ethnicity (n=424 and 154) were genotyped, and occurrence of previous manifestations of ischaemic heart disease (IHD), ischaemic cerebrovascular disease (ICVD) and venous thromboembolic events (VTE) was tabulated. aPL values were measured by ELISA. Matched controls (n=492 and 194) were genotyped.

    Results

    The STAT4 risk allele was more frequent in patients with SLE with previous arterial events (combined OR (ORc)=1.5, 95% CI 1.1 to 2.0) compared to patients without such events. The association was mainly attributable to an accumulation of the risk allele among patients with ICVD (ORc=2.3, CI 1.6 to 3.3). There was no association with IHD or VTE. The presence of two or more aPLs was associated with the risk allele (ORc=1.6, 95% CI 1.2 to 2.0). In multivariable-adjusted logistic regression analyses treatment for hypertension, at least one STAT4 risk allele, older age, IgG anti-cardiolipin antibodies and longer SLE duration remained independently associated with previous ICVD (p≤0.02 for all).

    Conclusion

    Patients with SLE with the STAT4 risk allele had a strikingly increased risk of ICVD, comparable in magnitude to that of hypertension. The results imply that a genetic predisposition is an important and previously unrecognised risk factor for ICVD in SLE, and that aPLs may be one underlying mechanism.

  • 166. Svenungsson, Elisabet
    et al.
    Lundström, Emeli
    Gustafsson, Johanna
    Jonsen, Andreas
    Leonard, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Zickert, Agneta
    Elvin, Kerstin
    Sturfelt, Gunnar
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Bengtsson, Anders
    Klareskog, Lars
    Gunnarsson, Iva
    Ronnblom, Lars
    Padyukov, Leonid
    Ischemic vascular disease and antiphospholipid antibodies are associated with HLA-DRB1 *04/*13 alleles in systemic lupus erythematosus2012Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, s. A57-A58Artikkel i tidsskrift (Annet vitenskapelig)
  • 167. Theander, Elke
    et al.
    Husmark, Tomas
    Alenius, Gerd-Marie
    Larsson, Per T.
    Teleman, Annika
    Geijer, Mats
    Lindqvist, Ulla R. C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Early psoriatic arthritis: short symptom duration, male gender and preserved physical functioning at presentation predict favourable outcome at 5-year follow-up. Results from the Swedish Early Psoriatic Arthritis Register (SwePsA)2014Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, nr 2, s. 407-413Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective

    The Swedish Early Psoriatic Arthritis Register describes the course of early psoriatic arthritis (PsA) in a real life clinical setting in Sweden. The aim of this study was to obtain information on predictors of clinical outcomes over a 5-year period with special focus on effects of gender, joint patterns, diagnostic delay and initial disease activity.

    Methods

    In six centres, patients with signs suggestive of PsA were included in the Swedish Early Psoriatic Arthritis Register within 2 years of symptom onset. CASPAR (classification for psoriatic arthritis) criteria were fulfilled by 197 patients who had passed the 5-year follow-up. Disease activity was measured by the Disease Activity Score including 28 joints (DAS28) and the Disease Activity Index for Psoriatic Arthritis (DAPSA). Remission and minimal disease activity (MDA) were used as outcome measures.

    Results

    Mean age at inclusion was 46 years, younger in male than female patients (43 vs 48 years). Mean DAS28 was 3.7 and 3.0 at inclusion and 2.8 and 2.1 at follow-up for women and men, respectively-significantly higher in women at both visits. Likewise, DAPSA scores were significantly higher in women. The degree of improvement (change in DAS28 and DAPSA) was similar. Men achieved MDA or remission (50% vs 33%, 25% vs 13%, respectively) more often, and women had significantly more polyarthritis at inclusion (49% vs 27%) and after 5 years (25% vs 15%). Axial or mono/oligoarticular disease was predominant in men. Independent predictors of MDA at the 5-year follow-up were: shorter symptom duration; greater general wellbeing (global visual analogue scale); and low Health Assessment Questionnaire at inclusion.

    Conclusions

    In early PsA, short delay between onset of symptoms and diagnosis, preserved function, and male gender are the most important predictors of favourable clinical outcome at the 5-year follow-up. Early recognition of PsA and active treatment may be important, particularly in women with polyarticular disease.

  • 168. Theander, Elke
    et al.
    Vasaitis, Lilian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Warfvinge, Gunnar
    Liedholm, Rolf
    Brokstad, Karl
    Jonsson, Roland
    Jonsson, Malin V.
    Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the development of malignant lymphoma in primary Sjogren's syndrome2011Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 70, nr 8, s. 1363-1368Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    The development of non-Hodgkin's lymphoma (NHL) confers a high risk of mortality in primary Sjögren's syndrome (pSS) patients, but the sensitivity and specificity of proposed lymphoma predictors are insufficient for practical use. The performance of lymphoid organisation in the form of germinal centre (GC)-like lesions was evaluated in labial salivary gland biopsies taken at pSS diagnosis as a potential lymphoma-predicting biomarker.

    METHODS:

    Labial salivary gland tissue biopsies available from two Swedish pSS research cohorts (n=175) were re-evaluated by light microscopy in a blind study in order to identify GC-like structures as a sign of ectopic lymphoid tissue formation and organisation. A linkage study was performed with the Swedish Cancer Registry for lymphoma identification. The risk of developing NHL in GC-positive patients in comparison with GC-negative patients was evaluated using Kaplan-Meier statistics and log-rank test. Associations between GC-like structures and clinical and/or laboratory disease markers were also determined using χ(2) or Fisher's exact tests.

    RESULTS:

    At diagnosis, 25% of pSS patients had GC-like structures in their salivary glands. Seven of the 175 patients studied (14% GC+ and 0.8% GC-) developed NHL during 1855 patient-years at risk, with a median onset of 7 years following the initial diagnostic salivary gland biopsy. Six of the seven patients had GC-like structures at diagnosis; the remaining patient was GC negative at the time of diagnosis (p=0.001).

    CONCLUSIONS:

    The detection of GC-like structures by light microscopy in pSS diagnostic salivary biopsies is proposed as a highly predictive and easy-to-obtain marker for NHL development. This allows for risk stratification of patients and the possibility to initiate preventive B-cell-directed therapy.

  • 169.
    Tjärnlund, Anna
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, S-17176 Stockholm, Sweden.
    Lundberg, Ingrid E.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, S-17176 Stockholm, Sweden.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Response to: 'Detection of myositis-specific antibodies: additional notes' by Infantino et al2019Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, nr 4, artikkel-id e30Artikkel i tidsskrift (Annet vitenskapelig)
  • 170.
    Tjärnlund, Anna
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Bottai, Matteo
    Karolinska Institutet, Stockholm, Sweden.
    Lundberg, Ingrid E.
    Karolinska Institutet, Stockholm, Sweden.
    Response to: ‘Detection of myositis-specific antibodies’ by Vulsteke et al2019Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, nr 1, artikkel-id UNSP e8Artikkel i tidsskrift (Annet vitenskapelig)
    Fulltekst (pdf)
    fulltext
  • 171.
    Tjärnlund, Anna
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Tang, Quan
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Wick, Cecilia
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Dastmalchi, Maryam
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Mann, Herman
    Inst Rheumatol, Dept Rheumatol, Prague, Czech Republic..
    Studynkova, Jana Tomasova
    Inst Rheumatol, Dept Rheumatol, Prague, Czech Republic..
    Chura, Radka
    Kings Coll Hosp NHS Fdn Trust, Dept Rheumatol, London, England..
    Gullick, Nicola J.
    Kings Coll Hosp NHS Fdn Trust, Dept Rheumatol, London, England..
    Salerno, Rosaria
    Kings Coll Hosp NHS Fdn Trust, Dept Rheumatol, London, England..
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Alexanderson, Helene
    Karolinska Inst, Dept Neurobiol, Div Physiotherapy, Stockholm, Sweden.;Karolinska Univ Hosp, Phys Therapy Clin, Stockholm, Sweden..
    Lindroos, Eva
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Aggarwal, Rohit
    Univ Pittsburgh, Sch Med, Div Rheumatol & Clin Rheumatol, Pittsburgh, PA USA..
    Gordon, Patrick
    Kings Coll Hosp NHS Fdn Trust, Dept Rheumatol, London, England..
    Vencovsky, Jiri
    Inst Rheumatol, Dept Rheumatol, Prague, Czech Republic..
    Lundberg, Ingrid E.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Abatacept in the treatment of adult dermatomyositis and polymyositis: a randomised, phase IIb treatment delayed-start trial2018Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, nr 1, s. 55-62Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: To study the effects of abatacept on disease activity and on muscle biopsy features of adult patients with dermatomyositis (DM) or polymyositis (PM).

    Methods: Twenty patients with DM (n=9) or PM (n=11) with refractory disease were enrolled in a randomised treatment delayed-start trial to receive either immediate active treatment with intravenous abatacept or a 3 month delayed-start. The primary endpoint was number of responders, defined by the International Myositis Assessment and Clinical Studies Group definition of improvement (DOI), after 6 months of treatment. Secondary endpoints included number of responders in the early treatment arm compared with the delayed treatment arm at 3 months. Repeated muscle biopsies were investigated for cellular markers and cytokines.

    Results: 8/19 patients included in the analyses achieved the DOI at 6 months. At 3 months of study, five (50%) patients were responders after active treatment but only one (11%) patient in the delayed treatment arm. Eight adverse events (AEs) were regarded as related to the drug, four mild and four moderate, and three serious AEs, none related to the drug. There was a significant increase in regulatory T cells (Tregs), whereas other markers were unchanged in repeated muscle biopsies.

    Conclusions: In this pilot study, treatment of patients with DM and PM with abatacept resulted in lower disease activity in nearly half of the patients. In patients with repeat muscle biopsies, an increased frequency of Foxp3(+) Tregs suggests a positive effect of treatment in muscle tissue.

  • 172.
    Too, C. L.
    et al.
    Inst Med Res, Allergy & Immunol Res Ctr, Immunogenet Unit, Kuala Lumpur, Malaysia..
    Manivel, Vivek Anand
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Persinidou, E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Murad, S.
    Minist Hlth Malaysia, Fed Govt Adm Ctr, Putrajaya, Malaysia..
    ANTI-COLLAGEN TYPE II ANTIBODIES ARE ASSOCIATED WITH EARLY INFLAMMATION IN MALAYSIAN RHEUMATOID ARTHRITIS PATIENTS WITH THREE DIFFERENT ETHINICITIES2018Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. A32-A33Artikkel i tidsskrift (Annet vitenskapelig)
  • 173. Turesson, C.
    et al.
    Bergstrom, U.
    Truedsson, L.
    Sohrabian, Azita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Jacobsson, L. T.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Patterns of Isotype Distribution in Circulating Antibodies in the Pre-Clinical Phase of Rheumatoid Arthritis and their Relation to Smoking2014Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, s. 510-510Artikkel i tidsskrift (Annet vitenskapelig)
  • 174. Turesson, C.
    et al.
    Jacobsson, L. T. H.
    Sturfelt, G.
    Matteson, E. L.
    Mathsson, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi och transfusionsmedicin.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi och transfusionsmedicin.
    Rheumatoid factor and antibodies to cyclic citrullinated peptides are associated with severe extra-articular manifestations in rheumatoid arthritis2007Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 66, nr 1, s. 59-64Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    ObjectiveTo study antibodies to cyclic citrullinated peptides (anti‐CCP) and rheumatoid factor in patients with active, severe extra‐articular rheumatoid arthritis (ExRA) compared with controls without ExRA.Methods35 consecutive patients with severe ExRA manifestations according to predefined criteria were studied. 70 patients with rheumatoid arthritis, but no ExRA manifestations, individually matched for age, sex and disease duration, served as controls. Patients were included when ExRA was diagnosed, before any new treatment was started. Anti‐CCPs were detected with ELISA, rheumatoid factor was quantified using nephelometry and anti‐nuclear antibodies (ANA) were investigated using indirect immune fluorescence.ResultsAnti‐CCPs were detected in 77% of patients with ExRA versus 56% of controls without ExRA (p=0.03). Anti‐CCP levels also tended to be higher in patients with ExRA (p=0.09). Rheumatoid factor was detected in 94% v 71% of patients and controls, respectively (p=0.006), and rheumatoid factor levels were higher in patients with ExRA (median interquartile range (IQR) 245 IU/ml (94–604) v 73 IU/ml (not detected–165); p=0.001). Levels and occurrence of ANA did not differ between patients with ExRA and controls. Patients with ExRA had higher swollen joint counts and C reactive protein levels, but no correlations were found between anti‐CCP or rheumatoid factor levels and these measures within the ExRA group.ConclusionRheumatoid factor is strongly associated with severe ExRA manifestations in patients with rheumatoid arthritis, and a similar but weaker association exists for anti‐CCPs. This suggests a role for rheumatoid factor and anti‐CCP in the pathogenesis of ExRA.

  • 175. Turesson, Carl
    et al.
    Mathsson, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Jacobsson, Lennart T. H.
    Sturfelt, Gunnar
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Antibodies to modified citrullinated vimentin are associated with severe extra-articular manifestations in rheumatoid arthritis2013Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 72, nr 12, s. 2047-2048Artikkel i tidsskrift (Fagfellevurdert)
  • 176.
    van Vollenhoven, Ronald F.
    et al.
    Karolinska Inst, Inflammatory Dis ClinTRID, Unit Clin Therapy Res, S-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Rheumatol Clin, Stockholm, Sweden..
    Ostergaard, Mikkel
    Univ Copenhagen, Glostrup Hosp, Ctr Rheumatol & Spine Dis, Fac Hlth Sci,Copenhagen Ctr Arthrit Res, Copenhagen, Denmark..
    Leirisalo-Repo, Marjatta
    Univ Helsinki, Cent Hosp, Helsinki, Finland.;Univ Helsinki, Inst Clin Med, Helsinki, Finland..
    Uhlig, Till
    Diakonhjemmet Hosp, Dept Rheumatol, Natl Advisory Unit Rehabil Rheumatol, Oslo, Norway..
    Jansson, Marita
    Pfizer Sweden, Sollentuna, Sweden..
    Larsson, Esbjorn
    Pfizer Sweden, Sollentuna, Sweden..
    Brock, Fiona
    Quanticate, Stat Consultancy, Hitchin, England..
    Franck-Larsson, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Full dose, reduced dose or discontinuation of etanercept in rheumatoid arthritis2016Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, nr 1, s. 52-58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The aim of the Dose Reduction or Discontinuation of Etanercept in Methotrexate-Treated Rheumatoid Arthritis Patients Who Have Achieved a Stable Low Disease Activity-State study was to investigate the effect of etanercept (ETN) dose maintenance, reduction or withdrawal on patients with rheumatoid arthritis (RA) who had already achieved stable low disease activity (LDA) on ETN 50 mg + methotrexate (MTX). Methods Patients with RA (n=91) and stable LDA with ETN 50 mg once weekly (QW)+ MTX were included. After 8 weeks with unchanged treatment, 73 patients were randomised in a double-blind design to ETN 50 mg QW+MTX (ETN50), ETN 25 mg QW+MTX (ETN25) or placebo QW+MTX (PBO) for 48 weeks. Patients who flared were declared failures and treated with open-label ETN50 until week 48. The primary outcome was the proportion of patients on ETN50 versus PBO who were non-failures after 48 weeks. Results The proportion of non-failure patients was significantly lower with ETN50 (52%; p=0.007) and ETN25 (44%; p=0.044) versus PBO (13%). Median time to failure was significantly shorter with PBO (6 weeks) compared with ETN50 (48 weeks; p=0.001) and ETN25 (36 weeks; p<0.001). The majority of patients who flared regained LDA with open-label ETN50 quickly. Adverse events were consistent with the known side effect profiles of these medications. Conclusions In patients with established RA who have achieved stable LDA on ETN50+MTX, continuing both is superior to PBO+MTX. Reduced dose ETN was also more effective than PBO in maintaining a favourable response, suggesting that a maintenance strategy with reduced dose ETN may be possible in a number of patients with established RA.

  • 177.
    Vasaitis, Lilian
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Theander, E.
    Lund Univ, Skane Univ Hosp, Dept Rheumatol, Malmo, Sweden..
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Smedby, K. E.
    Karolinska Inst, Dept Med Sci, Clin Epidemiol Unit, Stockholm, Sweden..
    Askling, J.
    Karolinska Inst, Dept Med Sci, Clin Epidemiol Unit, Stockholm, Sweden..
    Sundstrom, C.
    Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Primary Sjögren's Syndrome and Lymphoma – A Population-Based Study Focused on Lymphoma as Exclusion Criterion for Primary Sjögren's Syndrome Diagnosis2016Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, s. 779-780Artikkel i tidsskrift (Annet vitenskapelig)
  • 178. Wadström, Hjalmar
    et al.
    Frisell, Thomas
    Sparén, Pär
    Askling, Johan
    Do RA or TNF inhibitors increase the risk of cervical neoplasia or of recurrence of previous neoplasia? A nationwide study from Sweden2016Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, nr 7, s. 1272-1278Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To examine screening patterns and the risk of cervical neoplasia in women with rheumatoid arthritis (RA) treated or not with tumour necrosis factor inhibitors (TNFi).

    METHODS: We performed a nationwide register-based cohort study in Sweden of women with RA who started a first TNFi (n=9629), biologics-naive women with RA (n=34 984) and general population comparators (matched 1:10, n=300 331), followed up from 1999 to 2012. Outcomes were first cytology screening with normal outcome, first ever cervical intraepithelial neoplasia (CIN) grade 1, first ever CIN 2-3 or adenocarcinoma in situ and first ever invasive cervical cancer during follow-up. HRs were assessed through Cox regressions adjusted for age, educational level, prior cervical screens, comorbidities, marital status and prior hospitalisations.

    RESULTS: Biologic-naive women with RA had more screenings (HR 1.08, 95% CI 1.06 to 1.10), were at greater risk of CIN 1 (HR 1.53, 1.23 to 1.89) and CIN 2-3 (HR 1.39, 1.16 to 1.66), but not of invasive cervical cancer (HR 1.09, 0.71 to 1.65) compared with the general population. Patients who initiated TNFi therapy had similar screening patterns (HR 1.01, 0.98 to 1.05), were not at increased risk of CIN 1 (HR 1.23, 0.87 to 1.74), but were at increased risk of CIN 2-3 (HR 1.36, 1.01 to 1.82) and invasive cervical cancer (HR 2.10, 1.04 to 4.23) compared with biologics-naive women with RA. Estimates varied little with successive adjustments, but were attenuated/absent in sensitivity analyses restricted to 2006-2012 and a disease-modifying antirheumatic drugs-treated comparator.

    CONCLUSIONS: Women with RA in general are at elevated risk of cervical dysplasia. Compared with biologics-naive patients, women treated with TNFi are at increased risk of cervical cancer. Whether this increase is causally linked with TNFi could not be fully disentangled.

  • 179.
    Wahren, M.
    et al.
    Karolinska Inst, Stockholm, Sweden..
    Hedlund, M.
    Karolinska Inst, Stockholm, Sweden..
    Thorlacius, G. E.
    Karolinska Inst, Stockholm, Sweden..
    Ivanchenko, M.
    Karolinska Inst, Stockholm, Sweden..
    Kyriakidis, N.
    Karolinska Inst, Stockholm, Sweden..
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala Univ, Uppsala, Sweden..
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Espinosa, A.
    Karolinska Inst, Stockholm, Sweden..
    Sonesson, S. -E
    Type I IFN System Activation In Newborns Exposed To ANTI-RO/SSA Autoantibodies In Utero2017Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 182-182Artikkel i tidsskrift (Annet vitenskapelig)
  • 180. Wanders, Alkwin
    et al.
    Landewe, R
    Dougados, M
    Mielants, H
    van der Linden, S
    van der Heijde, D
    Association between radiographic damage of the spine and spinal mobility for individual patients with ankylosing spondylitis: can assessment of spinal mobility be a proxy for radiographic evaluation?2005Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 64, nr 7, s. 988-994Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    To demonstrate the association between various measures of spinal mobility and radiographic damage of the spine in individual patients with ankylosing spondylitis, and to determine whether the assessment of spinal mobility can be a proxy for the assessment of radiographic damage.

    METHODS:

    Radiographic damage was assessed by the mSASSS. Cumulative probability plots combined the radiographic damage score of an individual patient with the corresponding score for nine spinal mobility measures. Receiver operating characteristic analysis was performed to determine the cut off level of every spinal mobility measure that discriminates best between the presence and absence of radiographic damage. Three arbitrary cut off levels for radiographic damage were investigated. Likelihood ratios were calculated to explore further the diagnostic properties of the spinal mobility measures.

    RESULTS:

    Cumulative probability plots showed an association between spinal mobility measures and radiographic damage for the individual patient. Irrespective of the chosen cut off level for radiographic progression, lateral spinal flexion and BASMI discriminated best between patients with and those without structural damage. Even the best discriminatory spinal mobility assessments misclassified a considerable proportion of patients (up to 20%). Intermalleolar distance performed worst (up to 30% misclassifications). Lateral spinal flexion best predicted the absence of radiographic damage, and a modified Schober test best predicted the presence of radiographic damage.

    CONCLUSION:

    This study unequivocally demonstrated a relationship between spinal mobility and radiographic damage. However, spinal mobility cannot be used as a proxy for radiographic evaluation in an individual patient.

  • 181.
    Wang, Chuan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Sandling, Johanna K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Hagberg, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Berggren, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Sigurdsson, Snaevar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Karlberg, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Genome-wide profiling of target genes for the systemic lupus erythematosus-associated transcription factors IRF5 and STAT42013Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 72, nr 1, s. 96-103Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    The transcription factors interferon regulatory factor 5 (IRF5) and signal transducer and activator of transcription 4 (STAT4) are encoded by two of the strongest susceptibility genes for systemic lupus erythematosus (SLE).

    OBJECTIVE:

    To investigate the target genes and functional roles of IRF5 and STAT4 in human peripheral blood mononuclear cells (PBMCs).

    METHODS:

    Chromatin immunoprecipitation-sequencing (ChIP-seq) was performed in PBMCs stimulated to activate IRF5 and STAT4. The expression of the target genes of IRF5 and STAT4 was investigated in a publicly available dataset generated from PBMCs from patients with SLE and healthy controls. The genomic regions bound by the transcription complexes mediated by IRF5 and STAT4 were examined for transcription factor binding motifs and SLE-associated sequence variants.

    RESULTS:

    More than 7000 target genes for IRF5 and STAT4 were identified in stimulated PBMCs. These genes were enriched to functional pathways in the type I interferon system, and have key roles in the inflammatory response. The expression patterns of the target genes were characteristic for patients with SLE. The transcription factors high mobility group-I/Y, specificity protein 1, and paired box 4 may function cooperatively with IRF5 and STAT4 in transcriptional regulation. Eight of the target regions for IRF5 and STAT4 contain SLE-associated sequence variants.

    CONCLUSIONS:

    By participating in transcription complex with other co-factors, IRF5 and STAT4 harbour the potential of regulating a large number of target genes, which may contribute to their strong association with SLE.

  • 182. Webb, Ryan
    et al.
    Kelly, Jennifer A.
    Somers, Emily C.
    Hughes, Travis
    Kaufman, Kenneth M.
    Sanchez, Elena
    Nath, Swapan K.
    Bruner, Gail
    Alarcon-Riquelme, Marta E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Gilkeson, Gary S.
    Kamen, Diane L.
    Richardson, Bruce C.
    Harley, John B.
    Sawalha, Amr H.
    Early disease onset is predicted by a higher genetic risk for lupus and is associated with a more severe phenotype in lupus patients2011Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 70, nr 1, s. 151-156Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Systemic lupus erythematosus (SLE) is a chronic, multiorgan, autoimmune disease that affects people of all ages and ethnicities. Objectives To explore the relationship between age at disease onset and many of the diverse manifestations of SLE. Additionally, to determine the relationship between age of disease onset and genetic risk in patients with SLE. Methods The relationship between the age at disease onset and SLE manifestations were explored in a multiracial cohort of 1317 patients. Patients with SLE were genotyped across 19 confirmed genetic susceptibility loci for SLE. Logistic regression was used to determine the relationships between the number of risk alleles present and age of disease onset. Results Childhood-onset SLE had higher odds of proteinuria, malar rash, anti-dsDNA antibody, haemolytic anaemia, arthritis and leucopenia (OR=3.03, 2.13, 2.08, 2.50, 1.89, 1.53, respectively; p values < 0.0001, 0.0004, 0.0005, 0.0024, 0.0114, 0.045, respectively). In female subjects, the odds of having cellular casts were 2.18 times higher in childhood-onset than in adult-onset SLE (p=0.0027). With age of onset >= 50, the odds of having proteinuria, cellular casts, anti-nRNP antibody, anti-Sm antibody, anti-dsDNA antibody and seizures were reduced. However, late adult-onset patients with SLE have higher odds of developing photosensitivity than early adult-onset patients. Each SLE-susceptibility risk allele carried within the genome of patients with SLE increased the odds of having a childhood-onset disease in a race-specifi c manner: by an average of 48% in Gullah and 25% in African-Americans, but this was not significant in Hispanic and European-American lupus patients. Conclusions The genetic contribution towards predicting early-onset disease in patients with SLE is quantified for the first time. A more severe SLE phenotype is found in patients with early-onset disease in a large multi-racial cohort, independent of gender, race and disease duration.

  • 183.
    Weitoft, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Serum levels of sex steroid hormones and matrix metalloproteinases after intra-articular glucocorticoid treatment in female patients with rheumatoid arthritis2008Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 67, nr 3, s. 422-424Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To study metalloproteinase activity and sex steroid hormone production in serum after intra-articular glucocorticoid treatment for knee synovitis. METHODS: A total of 18 female patients with rheumatoid arthritis (RA) and synovitis of the knee with need for intra-articular glucocorticoid treatment were included in this study. Serum samples of matrix metalloproteinases (MMP-1/TIMP complex and MMP-3), dehydroepiandrosterone sulphate (DHEAS), testosterone, estradiol, steroid hormone binding globulin (SHBG), follicle stimulating hormone (FSH) and luteinizing hormone(LH) were collected before injection with 20 mg triamcinolone hexacetonide, and 24 hours, 48 hours, one week and two weeks after injection, respectively. RESULTS: Serum levels of MMP-3 were significantly decreased, but MMP-1/TIMP complex was unaffected. DHEAS, testosterone and estradiol levels all decreased and tended to return to baseline levels during the observation period. SHBG, FSH and LH levels were unchanged. CONCLUSION: Intra-articular glucocorticoid treatment causes a temporary, but considerable suppression of sex steroid hormone secretion. The reduction of MMP-3 indicates an inhibition of the inflammatory, but probably also the cartilage destructive processes within the treated joint.

  • 184.
    Weitoft, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Saxne, Tore
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Changes of cartilage and bone markers after intra- articular glucocorticoid treatment with and without postinjection rest in patients with rheumatoid arthritis2005Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 64, nr 12, s. 1750-1753Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Joint immobilisation improves the therapeutic effect of intra-articular glucocorticoid injection for knee synovitis. This may be due to retarded steroid resorption by immobilisation, a procedure that also could influence cartilage and bone metabolism. OBJECTIVE: To evaluate changes in cartilage and bone turnover after intra-articular glucocorticoid treatment for knee synovitis with and without postinjection rest. METHODS: 20 patients with rheumatoid arthritis and knee synovitis were randomised to 24 hour bed rest or to normal activity after intra-articular glucocorticoid treatment. Serum and urine markers of cartilage and bone turnover were studied for two weeks. Cartilage oligomeric matrix protein (COMP) was used as a marker of cartilage turnover, osteocalcin as marker of bone formation, and deoxipyridinoline (DPD) as marker of bone resorption. RESULTS: After the glucocorticoid injection COMP levels decreased in both groups (p<0.001), but significantly more in resting patients. Serum osteocalcin levels decreased significantly (p<0.001) without any difference between the groups. DPD was unchanged in both groups. CONCLUSIONS: Intra-articular glucocorticoid treatment for knee synovitis reduced serum COMP, which suggests that such treatment may have a cartilage protective effect. The slightly larger decrease of serum COMP in the resting group may reflect a lower clearance of COMP from the joint cavity. Serum osteocalcin was temporarily reduced, indicating a reversible suppression of bone formation.

  • 185.
    Weitoft, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Oberg, K.
    Falun Cent Hosp, Rheumatol Clin, Falun, Sweden.
    The dosing of intra-articular triamcinolone hexacetonide for knee synovitis in chronic polyarthritis: a randomized controlled study2018Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 987-987Artikkel i tidsskrift (Annet vitenskapelig)
  • 186.
    Yavuz, Sule
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Bianchi, Matteo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Kozyrev, Sergey
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bolin, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Leonard, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Pucholt, Pascal
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Sandling, Johanna K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bengtsson, Anders
    Jönsen, Andreas
    Rantapää-Dahlqvist, Solbritt
    Sjöwall, Christopher
    Svenungsson, Elisabet
    Gunnarsson, Iva
    Lindblad-Toh, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Toll-like receptors revisited: a possible role for TLR1 in lupus nephritis2021Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 80, nr 3, s. 404-406Artikkel i tidsskrift (Annet vitenskapelig)
    Fulltekst (pdf)
    fulltext
  • 187.
    Yavuz, Sule
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Biomarkers: to be or not to be2020Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 79, nr 1, artikkel-id e8Artikkel i tidsskrift (Fagfellevurdert)
  • 188. Ytterberg, A Jimmy
    et al.
    Joshua, Vijay
    Reynisdottir, Gudrun
    Tarasova, Nataliya K
    Rutishauser, Dorothea
    Ossipova, Elena
    Haj Hensvold, Aase
    Eklund, Anders
    Sköld, C Magnus
    Grunewald, Johan
    Malmström, Vivianne
    Jakobsson, Per Johan
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Padyukov, Leonid
    Zubarev, Roman A
    Klareskog, Lars
    Catrina, Anca I
    Shared immunological targets in the lungs and joints of patients with rheumatoid arthritis: identification and validation2015Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 74, nr 9, s. 1772-1777Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Immunological events in the lungs might trigger production of anti-citrullinated protein antibodies during early rheumatoid arthritis (RA). We investigated the presence of shared immunological citrullinated targets in joints and lungs of patients with RA.

    PATIENTS AND METHODS: Proteins extracted from bronchial (n=6) and synovial (n=7) biopsy specimens from patients with RA were investigated by mass spectrometry-based proteomics. One candidate peptide was synthesised and used to investigate by ELISA the presence of antibodies in patients with RA (n=393), healthy controls (n=152) and disease controls (n=236). HLA-DRB1 shared epitope (SE) alleles were detected in patients with RA.

    RESULTS: Ten citrullinated peptides belonging to seven proteins were identified, with two peptides shared between the synovial and bronchial biopsy samples. Further analysis, using accurate mass and retention time, enabled detection of eight citrullinated peptides in synovial and seven in bronchial biopsy specimens, with five peptides shared between the synovial and bronchial biopsy specimens. Two citrullinated vimentin (cit-vim) peptides were detected in the majority of synovial and lung tissues. Antibodies to a synthesised cit-vim peptide candidate (covering both cit-vim peptides identified in vivo) were present in 1.8% of healthy controls, 15% of patients with RA, and 3.4% of disease controls. Antibodies to cit-vim peptide were associated with the presence of the SE alleles in RA.

    CONCLUSIONS: Identical citrullinated peptides are present in bronchial and synovial tissues, which may be used as immunological targets for antibodies of patients with RA. The data provide further support for a link between lungs and joints in RA and identify potential targets for immunity that may mediate this link.

  • 189. Zickert, A.
    et al.
    Amoudruz, P.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Malmström, V.
    Gunnarsson, I.
    Cytokines in lupus nephritis, levels of IL-17 and IL-23 in association to histopathology and response to treatment2012Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, s. A4-A5Artikkel i tidsskrift (Annet vitenskapelig)
  • 190. Ärlestig, Lisbeth
    et al.
    Mullazehi, Mohammed
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Kokkonen, Heidi
    Rocklöv, Joacim
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Rantapää Dahlqvist, Solbritt
    Antibodies against cyclic citrullinated peptides of IgG, IgA and IgM isotype and rheumatoid factor of IgM and IgA isotype are increased in unaffected members of multicase rheumatoid arthritis families from northern Sweden2012Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, nr 6, s. 825-829Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Rheumatoid factors (RFs) and antibodies against cyclic citrullinated peptides (CCPs) of IgG, IgA and IgM isotype have been shown to precede disease onset by years.

    OBJECTIVE:

    To evaluate serological risk markers in first-degree relatives from multicase families in relation to genetic and environmental risk factors.'

    METHODS:

    51 multicase families consisting of 163 individuals with rheumatoid arthritis (RA) (mean±SD age, 60±14 years; disease duration 21 years; 71.8% female) and with 157 first-degree relatives unaffected by RA (54±17 years; 59.9% female) were recruited. Isotypes of antibodies against CCPs (IgG, IgA and IgM) and RFs (IgM and IgA) were determined using automated enzyme immunoassays. Cut-off levels were established using receiver operating characteristic curves based on values for 100 unrelated healthy controls.

    RESULTS:

    The concentrations and frequencies of all anti-CCP and RF isotypes were significantly increased in first-degree relatives and patients with RA compared with unrelated healthy controls. The relative distribution of IgA and IgM isotypes was higher than IgG in the relatives, whereas the IgG isotype dominated in patients with RA. The patients carried human leucocyte antigen-shared epitope (HLA-SE) significantly more often than the relatives (71.4% vs 53.9%, p=0.01), while the frequency of the PTPN22 T variant was similar. HLA-SE, combined with smoking, was significantly related to all combinations of anti-CCP and RF isotypes in patients with RA. No such relationships were found for the first-degree relatives.

    CONCLUSIONS:

    All anti-CCP and RF isotypes analysed occurred more commonly in unaffected first-degree relatives from multicase families than in controls, but with different isotype distribution from patients with RA.

  • 191.
    Åsenlöf, Pernilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    The Ongoing Shift of Paradigms within Physiotherapy and Pain Management2016Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, s. 29-29Artikkel i tidsskrift (Annet vitenskapelig)
  • 192.
    Åsenlöf, Pernilla
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Bergman, P.
    Demmelmaier, I.
    Jensen, I.
    Nordgren, B.
    Opava, C. H.
    SEDENTARY TIME AMONG ADULTS WITH RHEUMATOID ARTHRITIS. THE PARA 2010 STUDY2013Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 72, nr S3, s. 766-766Artikkel i tidsskrift (Annet vitenskapelig)
  • 193.
    Åsenlöf, Pernilla
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Demmelmaier, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Emilson, Christina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Pettersson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Bergman, S.
    Step-Up: An Innovative Stepped-Care Protocol for Tailored Behavioral Medicine Treatment in the Management of Musculoskeletal Pain in Primary Care2013Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 72, s. 1041-1041Artikkel i tidsskrift (Annet vitenskapelig)
  • 194.
    Åsenlöf, Pernilla
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Demmelmaier, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Emilson, Christina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Pettersson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Bergman, S.
    Step-Up: An Innovative Stepped-Care Protocol for Tailored Behavioral Medicine Treatment in The Management of Musculoskeletal Pain in Primary Care2013Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 72, nr S3, s. 120-120Artikkel i tidsskrift (Annet vitenskapelig)
1234 151 - 194 of 194
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