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  • 1.
    Eriksson, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kozyrev, Sergey V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Dahlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Broad Inst Harvard & MIT, Cambridge, MA USA.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    A case of systemic lupus erythematosus with C1q deficiency, increased serum interferon-a levels and high serum interferogenic activity2019In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 58, no 5, p. 918-919Article in journal (Other academic)
  • 2.
    Hagberg, Niklas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Theorell, Jakob
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Pascal, Veronique
    Bryceson, Yenan T
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Anti-NKG2A autoantibodies in a patient with systemic lupus erythematosus2013In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 52, no 10, p. 1818-1823Article in journal (Refereed)
    Abstract [en]

    Objectives

    To characterize a novel anti-NKG2A autoantibody detected in a patient with SLE during a severe flare, and in a cross-sectional study investigate the occurrence of such autoantibodies in patients with SLE and primary SS (pSS).

    Methods

    Serum or IgG from patients with SLE, pSS and healthy volunteers were assayed for blocking of anti-NKG2A or HLA-E binding to peripheral blood mononuclear cells or CD94/NKG2A- and CD94/NKG2C-transfected Ba/F3 cells. The anti-NKG2A autoantibodies were evaluated for effect on NK cell degranulation in response to HLA-E-transfected K562 cells. IFN-α was determined by an immunoassay and disease activity by the SLEDAI score.

    Results

    Anti-NKG2A autoantibodies, which blocked binding of HLA-E tetramers to CD94/NKG2A-transfected cells and impaired NKG2A-mediated inhibition of NK cell activation, were observed in a patient with SLE. The presence of anti-NKG2A autoantibodies was associated with high SLE disease activity (SLEDAI score 14 and 16) and increased serum IFN-α. Of 94 SLE, 60 pSS and 30 healthy donor sera, only the index patient serum contained anti-NKG2A autoantibodies.

    Conclusion

    The presence of autoantibodies targeting NKG2A is a rare event, but when such autoantibodies occur they may promote excessive NK cell function. This can contribute to the pathogenesis by increasing the killing of cells and the release of autoantigens. Our findings highlight the possible importance of NK cells in the SLE disease process.

  • 3.
    Hellbacher, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hjorton, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Malignant Lymphoma In Granulomatosis With Polyangiitis2017In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 56Article in journal (Refereed)
  • 4.
    Imgenberg-Kreuz, Juliana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Genetics and epigenetics in primary Sjögren's syndrome.2019In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, article id key330Article in journal (Refereed)
    Abstract [en]

    Primary Sjögren's syndrome (pSS) is considered to be a multifactorial disease, where underlying genetic predisposition, epigenetic mechanisms and environmental factors contribute to disease development. In the last 5 years, the first genome-wide association studies in pSS have been completed. The strongest signal of association lies within the HLA genes, whereas the non-HLA genes IRF5 and STAT4 show consistent associations in multiple ethnicities but with a smaller effect size. The majority of the genetic risk variants are found at intergenic regions and their functional impact has in most cases not been elucidated. Epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNAs play a role in the pathogenesis of pSS by their modulating effects on gene expression and may constitute a dynamic link between the genome and phenotypic manifestations. This article reviews the hitherto published genetic studies and our current understanding of epigenetic mechanisms in pSS.

  • 5.
    Kharazmi, Mohammad
    et al.
    Department of Oral and Maxillofacial Surgery, Central Hospital, Västerås, Sweden.
    Hallberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Warfvinge, Gunnar
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Risk of atypical femoral fractures and osteonecrosis of the jaw associated with alendronate use compared with other oral bisphosphonates2014In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 53, no 10, p. 1911-1913Article in journal (Refereed)
  • 6.
    Knight, Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Pauksen, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Eva, Kumlien
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Fatal outcome of tick-borne encephalitis in two patients with rheumatic disease treated with rituximab2017In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 56, no 5, p. 855-856Article in journal (Refereed)
  • 7.
    Larsson, Susanna C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol, S-17177 Stockholm, Sweden.
    Burgess, Stephen
    Univ Cambridge, MRC Biostat Unit, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Genetic association between adiposity and gout: a Mendelian randomization study2018In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 57, no 12, p. 2145-2148Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate whether overall obesity (as measured by BMI) and abdominal obesity (as measured by waist-to-hip ratio adjusted for BMI) are associated with gout risk and serum urate concentrations using Mendelian randomization.

    Methods: Single nucleotide polymorphisms associated with BMI (n = 97) and waist-to-hip ratio adjusted for BMI (n = 49) were analysed for association with gout risk in 2115 gout cases and 67 259 controls, and with serum urate concentrations in 110 347 individuals from the Global Urate Genetics Consortium.

    Results: Genetically higher BMI, but not waist-to-hip ratio adjusted for BMI, was positively associated with risk of gout and serum urate concentrations. Each standard deviation (about 4.6 kg/m(2)) increase in genetically predicted BMI was associated with an odds ratio of gout of 2.24 (95% CI 1.70, 2.95; P = 8.4 x 10(-9)) and with a 0.30 mg/dl (95% CI 0.25, 0.35; P = 1.6 x 10(-36)) increase in serum urate concentrations.

    Conclusion: These findings provide support that overall obesity may be a risk factor for gout and is associated with higher serum urate concentrations.

  • 8. Löfström, Björn
    et al.
    Backlin, Carin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Hellström-Lindberg, Eva
    Ekbom, Anders
    Lundberg, Ingrid E
    Myeloid leukaemia in systemic lupus erythematosus--a nested case-control study based on Swedish registers2009In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 48, no 10, p. 1222-1226Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess the risk factors for leukaemic transformation and myeloid leukaemia in patients with SLE. METHODS: A national SLE cohort identified through SLE discharge diagnoses in the Swedish hospital discharge register during 1964 to 1995 (n = 6438) was linked to the national cancer register. A nested case-control study in SLE patients who developed acute or chronic myeloid leukaemia was performed with SLE patients without malignancy as controls. Medical records from cases and controls were reviewed and bone marrow specimens were re-evaluated. A Medline search of previously published cases of SLE and myeloid leukaemia was performed. RESULTS: After confirmation of SLE diagnosis according to the ACR criteria, eight patients with SLE and myeloid leukaemia and 18 SLE controls were included in the study. Preceding leucopenia was significantly associated with leukaemia development, whereas other SLE manifestations were not. Two cases had a preceding bone marrow confirming myelodysplastic syndrome (MDS). Only two cases were significantly treated with cyclophosphamide or AZA. A Medline search resulted in only 15 previously published cases of coincident SLE and myeloid leukaemia. Preceding MDS was reported in five of these, whereas only eight had been treated with cytotoxic drugs. CONCLUSION: Low-dose chemotherapy was not a major cause of myeloid malignancy in our population-based cohort of SLE patients nor in the reported cases from literature. Leucopenia was a risk factor for myeloid leukaemia development and an MDS was frequently seen. Therefore bone marrow investigation should be considered in SLE patients with long-standing leucopenia and anaemia.

  • 9.
    Mercer, Louise
    et al.
    Univ Manchester, Arthrit Res UK Ctr Epidemiol, Manchester, Lancs, England..
    Mariette, Xavier
    Univ Paris 11, Dept Rheumatol, Paris, France..
    Dixon, Will
    Univ Manchester, Arthrit Res UK Ctr Epidemiol, Manchester, Lancs, England..
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hellgren, Karin
    Karolinska Inst, Clin Epidemiol Unit, Stockholm, Sweden..
    Dreyer, Lene
    Gentofte Univ Hosp, Dept Rheumatol, Hellerup, Denmark..
    Hetland, Merete
    Univ Copenhagen, Copenhagen Ctr Arthrit Res, DANBIO, DK-1168 Copenhagen, Denmark..
    Mellemkjaer, Lene
    Danish Canc Soc, Danish Canc Soc Res Ctr, Copenhagen, Denmark..
    Hyrich, Kimme
    Univ Manchester, Arthrit Res UK Ctr Epidemiol, Manchester, Lancs, England..
    Strangfeld, Anja
    German Rheumatism Res Ctr, Epidemiol Unit, Berlin, Germany..
    Zink, Angela
    German Rheumatism Res Ctr, Epidemiol Unit, Berlin, Germany..
    Canhao, Helena
    Univ Lisbon, Rheumatol Res Unit, P-1699 Lisbon, Portugal..
    Martins, Fernando
    Univ Lisbon, Rheumatol Res Unit, P-1699 Lisbon, Portugal..
    Hernandez, Victoria
    BIOBADASER Registry, Madrid, Spain..
    Tubach, Florence
    Univ Paris Diderot, Dept Epidemiol & Rech Clin, Paris, France..
    Gottenberg, Jacques-Eric
    CHU, Dept Rheumatol, Strasbourg, France..
    Morel, Jacques
    Univ Montpellier, F-34059 Montpellier, France..
    Zavada, Jakub
    Charles Univ Prague, Inst Rheumatol, Prague, Czech Republic..
    van Riel, Piet
    Radboud Univ Nijmegen, Dept Rheumat Dis, NL-6525 ED Nijmegen, Netherlands. Univ Geneva, Geneva, Switzerland..
    Finckh, Axel
    Univ Manchester, Arthrit Res UK Ctr Epidemiol, Manchester, Lancs, England.;Univ Copenhagen, Copenhagen Ctr Arthrit Res, DANBIO, DK-1168 Copenhagen, Denmark..
    Iannone, Florenzo
    Univ Bari, Bari, Italy..
    Askling, Johan
    Karolinska Inst, Clin Epidemiol Unit, Stockholm, Sweden..
    Listing, Joachim
    German Rheumatism Res Ctr, Epidemiol Unit, Berlin, Germany..
    First Results Of A European Registries Collaborative Project To Describe The Spectrum Of Lymphomas Across Different Drug Treatment Groups In Rheumatoid Arthritis2015In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 54, p. 25-25Article in journal (Other academic)
  • 10.
    Norheim, Katrine Braekke
    et al.
    Stavanger Univ Hosp, Clin Immunol Unit, Dept Internal Med, Pb 8100 Forus, N-4068 Stavanger, Norway..
    Imgenberg-Kreuz, Juliana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Jonsdottir, Kristin
    Stavanger Univ Hosp, Dept Pathol, N-4068 Stavanger, Norway..
    Janssen, Emiel A. M.
    Stavanger Univ Hosp, Dept Pathol, N-4068 Stavanger, Norway..
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Omdal, Roald
    Stavanger Univ Hosp, Clin Immunol Unit, Dept Internal Med, Pb 8100 Forus, N-4068 Stavanger, Norway..
    Epigenome-wide DNA methylation patterns associated with fatigue in primary Sjogren's syndrome2016In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 55, no 6, p. 1074-1082Article in journal (Refereed)
    Abstract [en]

    Objective. Chronic fatigue is a common, disabling and poorly understood phenomenon. Recent studies indicate that epigenetic mechanisms may be involved in the expression of fatigue, a prominent feature of primary SS (pSS). The aim of this study was to investigate whether DNA methylation profiles of whole blood are associated with fatigue in patients with pSS. Methods. Forty-eight pSS patients with high (n = 24) or low (n = 24) fatigue as measured by a visual analogue scale were included. Genome-wide DNA methylation was investigated using the Illumina HumanMethylation450 BeadChip array. After quality control, a total of 383 358 Cytosine-phosphate-Guanine (CpG) sites remained for further analysis. Age, sex and differential cell count estimates were included as covariates in the association model. A false discovery rate-corrected P < 0.05 was considered significant, and a cut-off of 3% average difference in methylation levels between high- and low-fatigue patients was applied. Results. A total of 251 differentially methylated CpG sites were associated with fatigue. The CpG site with the most pronounced hypomethylation in pSS high fatigue annotated to the SBF2-antisense RNA1 gene. The most distinct hypermethylation was observed at a CpG site annotated to the lymphotoxin alpha gene. Functional pathway analysis of genes with differently methylated CpG sites in subjects with high vs low fatigue revealed enrichment in several pathways associated with innate and adaptive immunity. Conclusion. Some genes involved in regulation of the immune system and in inflammation are differently methylated in pSS patients with high vs low fatigue. These findings point to functional networks that may underlie fatigue. Epigenetic changes could constitute a fatigue-regulating mechanism in pSS.

  • 11.
    Parodis, Ioannis
    et al.
    Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet..
    Gokaraju, Sirisha
    Department of Biomedical Engineering, University of Houston, Houston, TX, USA..
    Zickert, Agneta
    Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet..
    Vanarsa, Kamala
    Department of Biomedical Engineering, University of Houston, Houston, TX, USA..
    Zhang, Ting
    Department of Biomedical Engineering, University of Houston, Houston, TX, USA..
    Habazi, Deena
    Department of Biomedical Engineering, University of Houston, Houston, TX, USA..
    Botto, João
    Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet..
    Serdoura Alves, Clara
    Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet..
    Giannopoulos, Panagiotis
    Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Svenungsson, Elisabet
    Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet..
    Gunnarsson, Iva
    Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet..
    Mohan, Chandra
    Department of Biomedical Engineering, University of Houston, Houston, TX, USA..
    ALCAM and VCAM-1 as urine biomarkers of activity and long-term renal outcome in systemic lupus erythematosus.2019In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, article id kez528Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: We investigated the cell adhesion molecules (CAMs) Vascular CAM 1 (VCAM-1) and Activated Leucocyte CAM (ALCAM) as urinary biomarkers in SLE patients with and without renal involvement.

    METHODS: Female SLE patients (n = 111) and non-SLE population-based controls (n = 99) were enrolled. We measured renal activity using the renal domain of the BILAG index and urine (U) and plasma (P) concentrations of soluble (s)VCAM 1 and U-sALCAM using ELISA. U-sCAM levels were next corrected by U-creatinine.

    RESULTS: U-sVCAM-1/creatinine and U-sALCAM/creatinine ratios were higher in SLE patients vs non-SLE controls (P < 0.001 for both), as well as in patients with active/low-active (BILAG A-C; n = 11) vs quiescent (BILAG D; n = 19) LN (P = 0.023 and P = 0.001, respectively). U-sALCAM/creatinine but not U-sVCAM-1/creatinine ratios were higher in patients with nephritis history (BILAG A-D; n = 30) vs non-renal SLE (BILAG E; n = 79) (P = 0.014). Patients with baseline U-sVCAM-1/creatinine ratios ≥75th percentile showed a 23-fold increased risk of a deterioration in estimated glomerular filtration rate by ≥25% during a 10-year follow-up (odds ratio: 22.9; 95% CI: 2.8, 189.2; P = 0.004); this association remained significant after adjustments for age, disease duration and organ damage. Traditional markers including anti-dsDNA antibodies did not predict this outcome.

    CONCLUSION: While high U-sVCAM-1 levels appear to reflect SLE disease activity, sALCAM might have particular importance in renal SLE. Both U-sVCAM-1 and U-sALCAM showed ability to distinguish SLE patients with active renal involvement from patients with quiescent or no prior nephritis. High U-sVCAM-1 levels may indicate patients at increased risk for long-term renal function loss.

  • 12. Pettersson, Susanne
    et al.
    Möller, Sonia
    Svenungsson, Elisabet
    Gunnarsson, Iva
    Welin Henriksson, Elisabet
    Women's experience of SLE-related fatigue: a focus group interview study.2010In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 49, no 10, p. 1935-42Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to describe women's experience of SLE-related fatigue, how they express the feeling of fatigue, impact on life and strategies developed to manage fatigue in daily living.

    METHOD: Seven, semi-structured focus group discussions with 33 women were audio-taped, transcribed verbatim and analysed according to qualitative content analysis.

    RESULTS: Perceptions of SLE-related fatigue were sorted into four themes. Nature of Fatigue, involved the sensation, occurrence and character. Aspects Affected by Fatigue described emotions that arose together with fatigue as well as aspects of work, family life, social contacts and leisure activities that were affected by fatigue. Striving Towards Power and Control concluded the array of ways used to manage daily life and were categorized into the mental struggle, structure, restrict and provide. Factors Influencing the Perception of Fatigue described understanding from their surroundings and pain as strongly influencing the experience and perception of fatigue.

    CONCLUSION: SLE-related fatigue was portrayed as an overwhelming phenomenon with an unpredictable character, resulting in the feeling that fatigue dominates and controls most situations in life. The choice of strategies was described as a balance with implications for how fatigue limited a person's life. Health care professionals are advised to take a more active role to empower people with SLE to find their own balance as a way to achieve a feeling of being in control.

  • 13. Phuong, Thuy Nguyen Thi
    et al.
    Ngoc, Lan Nguyen Thi
    Xuan, Hien Nguyen
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Padyukov, Leonid
    Dept Med, Div Rheumatol, Solna, Sweden;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.
    Lundberg, Ingrid E.
    Dept Med, Div Rheumatol, Solna, Sweden;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden;Karolinska Univ Hosp, Rheumatol Clin, Stockholm, Sweden.
    Clinical phenotype, autoantibody profile and HLA-DR-type in Vietnamese patients with idiopathic inflammatory myopathies2019In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 58, no 2, p. 361-363Article in journal (Other academic)
  • 14. Simard, Julia F.
    et al.
    Arkema, Elizabeth V.
    Sundström, Anders
    Geborek, Pierre
    Saxne, Tore
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Coster, Lars
    Dackhammar, Christina
    Jacobsson, Lennart
    Feltelius, Nils
    Lindblad, Staffan
    Rantapää-Dahlqvist, Solbritt
    Klareskog, Lars
    van Vollenhoven, Ronald F.
    Neovius, Martin
    Askling, Johan
    Ten years with biologics: to whom do data on effectiveness and safety apply?2011In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 50, no 1, p. 204-213Article in journal (Refereed)
    Abstract [en]

    Methods. We identified all adult patients with RA (n = 9612), PsA (n = 1417) and other SpA (n = 1652) initiating a first biologic therapy between 1 January 1999 and 31 December 2008, registered in the Swedish Biologics Register (ARTIS), including information on demographics, disease characteristics and 1-year risk of first-line treatment discontinuation. Results. Over calendar time, measures of disease activity at start declined substantially for all indications, and diminished between first-, second- and third-line therapy starts. One-year risks of first-line therapy discontinuation increased. Switchers to anti-TNF and non-TNF biologics had different comorbidities. Despite < 50% drug retention at 5 years, most patients remained exposed to some biologic. Conclusions. The trends in baseline characteristics and drug retention underscores that any effects of biologics, including comparison between different biologics, must be interpreted in light of the characteristics of the population treated. The observed differences further call for continued vigilance to properly evaluate the safety profiles of biologic treatments as they are currently used. Exposure to multiple biologics presents a challenge for attribution of long-term effects.

  • 15.
    Stack, Rebecca J.
    et al.
    Univ Birmingham, Ctr Translat Inflammat Res, Birmingham, W Midlands, England..
    Falahee, Marie
    Univ Birmingham, Ctr Translat Inflammat Res, Birmingham, W Midlands, England..
    Stoffer, Michaela
    Med Univ Vienna, Div Rheumatol, Vienna, Austria..
    Stamm, Tanja
    Med Univ Vienna, Div Rheumatol, Vienna, Austria..
    Simons, Gwenda
    Univ Birmingham, Ctr Translat Inflammat Res, Birmingham, W Midlands, England..
    Buckley, Christopher
    Univ Birmingham, Ctr Translat Inflammat Res, Birmingham, W Midlands, England..
    Kumar, Kanta
    Univ Manchester, Sch Nursing, Manchester, Lancs, England..
    Hansson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Raza, Karim
    Univ Birmingham, Ctr Translat Inflammat Res, Birmingham, W Midlands, England..
    Perceptions Of Testing To Predict Future Development Of Rheumatoid Arthritis Among The First-Degree Relatives Of People With Rheumatoid Arthritis: A Qualitative Exploration2015In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 54, p. 110-110Article in journal (Refereed)
  • 16. Stening, Kent D.
    et al.
    Eriksson, Olle
    Henriksson, Karl G.
    Brynhildsen, Jan
    Lindh-Åstrand, Lotta
    Berg, Göran
    Hammar, Mats
    Amandusson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Blomqvist, Anders
    Hormonal replacement therapy does not affect self-estimated pain or experimental pain responses in post-menopausal women suffering from fibromyalgia: a double-blind, randomized, placebo-controlled trial2011In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 50, no 3, p. 544-551Article in journal (Refereed)
    Abstract [en]

    Objectives. FM is a condition that preferentially affects women. Sex hormones, and in particular oestrogens, have been shown to affect pain processing and pain sensitivity, and oestrogen deficit has been considered a potentially promoting factor for FM. However, the effects of oestrogen treatment in patients suffering from FM have not been studied. Here, we examined the effect of transdermal oestrogen substitution treatment on experimental as well as self-estimated pain in women suffering from FM. Methods. Twenty-nine post-menopausal women were randomized to either 8 weeks of treatment with transdermal 17β-oestradiol (50 µg/day) or placebo according to a double-blind protocol. A self-estimation of pain, a set of quantitative sensory tests measuring thresholds to temperature, thermal pain, cold pain and pressure pain, and a cold pressor test were performed on three occasions: before treatment, after 8 weeks of treatment and 20 weeks after cessation of treatment. Results. Hormonal replacement treatment significantly increased serum oestradiol levels as expected (P < 0.01). However, no differences in self-estimated pain were seen between treatment and placebo groups, nor were there any differences between the two groups regarding the results of the quantitative sensory tests or the cold pressor test at any of the examined time points. Conclusion. Eight weeks of transdermal oestradiol treatment does not influence perceived pain, pain thresholds or pain tolerance as compared with placebo treatment in post-menopausal women suffering from FM. Trial registration. ClinicalTrials.gov Registration; http://www.clinicaltrials.gov; NCT01087593.

  • 17. Vikerfors, Anna
    et al.
    Johansson, Anna-Britta
    Gustafsson, Johanna T
    Jönsen, Andreas
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Zickert, Agneta
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Sturfelt, Gunnar
    Bengtsson, Anders
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Gunnarsson, Iva
    Elvin, Kerstin
    Svenungsson, Elisabet
    Clinical manifestations and anti-phospholipid antibodies in 712 patients with systemic lupus erythematosus: evaluation of two diagnostic assays2013In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 34, no 5, p. 345-353Article in journal (Refereed)
    Abstract [en]

    Objectives

    To evaluate the agreement and performance of two tests for aPLs with regard to association with manifestations of the APS in patients with SLE.

    Methods

    We investigated 712 SLE patients and 280 population controls. Cardiolipin and β2 glycoprotein-I antibodies were measured with routine ELISA and a new automated method. Three positivity cut-offs (99%, 90% of controls and recommended cut-off by manufacturers) were used. Associations with previous thrombotic events, thrombocytopenia and, in a subgroup of patients, obstetric morbidity (n = 296) were evaluated. Results were compared with the LA test, performed in 380 patients.

    Results

    Inter-test agreement was moderate (demonstrated by κ-values 0.16–0.71). Performance of the two tests was similar: at the 99th percentile cut-off, sensitivity for any thrombotic event ranged from 3.7% to 24.8%, while specificity was 84.7–97.7%. Regardless of assay, IgG isotypes were associated with venous thrombosis and ischaemic cerebrovascular disease, whereas aPLs of IgM isotype were weakly associated with ischaemic heart disease. Associations were greatly affected by aPL level. LA performed better than the specific aPL tests. LA was associated with any thrombotic event, odds ratio 5.4 (95% CI 3.1, 9.4), while the specific aPL tests ranged from non-significant to an odds ratio of 1.9 (95% CI 1.03, 3.4) using criteria cut-off. LA was also convincingly associated with other APS manifestations.

    Conclusion

    In relation to thrombotic manifestations, there was moderate agreement but no clear advantages when comparing a routine aPL ELISA with an automated method. APL isotype and titre as well as LA positivity are important for risk assessment in SLE patients.

  • 18.
    Weitoft, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Manivel, Vivek A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lysholm, Jörgen
    Clinic of Rheumatology, Falun Hospital, Falun.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Cathepsin S and cathepsin L in serum and synovial fluid in rheumatoid arthritis with and without autoantibodies2015In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 54, no 10, p. 1923-1928Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Cathepsin S and cathepsin L are endosomal proteolytic enzymes involved in the degradation of extracellular matrixes, angiogenesis and antigen presentation. Cathepsins could thus play several roles in the disease process of RA. The aim of this study was to examine differences in cathepsin S and cathepsin L levels in serum and SF of RA patients with and without ACPA and RF.

    METHODS: In this study 121 patients with RA and clinical signs of knee synovitis were recruited. Patient characteristics were collected and matched samples of serum and SF were analysed for cathepsin S, cathepsin L, ACPA, IgA and IgM RF, CRP and MMP3.

    RESULTS: SF levels of cathepsin L, cathepsin S and MMP3 were significantly higher than in serum. Serum levels of both cathepsins were significantly higher in patients with ACPA, IgM-RF and IgA-RF compared with patients without these antibodies. SF levels of both cathepsins correlated with DAS28 and CRP in ACPA- and RF-positive but not in seronegative patients.

    CONCLUSION: The differences in cathepsin S and cathepsin L between RA patients with and without autoantibodies indicate that these cathepsins have a specific role in the disease process of seropositive RA. In this phenotype, cathepsin serum levels may reflect the autoimmune activity, whereas the levels in SF may reflect the local inflammatory and matrix degrading process in the joint.

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