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Tjärnlund, A., Tang, Q., Wick, C., Dastmalchi, M., Mann, H., Studynkova, J. T., . . . Lundberg, I. E. (2018). Abatacept in the treatment of adult dermatomyositis and polymyositis: a randomised, phase IIb treatment delayed-start trial. Annals of the Rheumatic Diseases, 77(1), 55-62
Open this publication in new window or tab >>Abatacept in the treatment of adult dermatomyositis and polymyositis: a randomised, phase IIb treatment delayed-start trial
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2018 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, no 1, p. 55-62Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP, 2018
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-338993 (URN)10.1136/annrheumdis-2017-211751 (DOI)000417778700013 ()28993346 (PubMedID)
Funder
Swedish Research Council, GRANTK2014-52X-14045-14-3Swedish Rheumatism AssociationStockholm County CouncilThe Karolinska Institutet's Research Foundation
Available from: 2018-01-17 Created: 2018-01-17 Last updated: 2018-02-27Bibliographically approved
Baecklund, E., Backlin, C., Rönnelid, J., Toes, R., Huizinga, T., Åhlin, E., . . . Smedby, K. E. (2018). Anti-cyclic citrullinated peptide antibodies, other common autoantibodies, and smoking as risk factors for lymphoma in patients with rheumatoid arthritis. Scandinavian Journal of Rheumatology
Open this publication in new window or tab >>Anti-cyclic citrullinated peptide antibodies, other common autoantibodies, and smoking as risk factors for lymphoma in patients with rheumatoid arthritis
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2018 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of lymphoma. There is no biomarker to indicate future lymphoma risk in RA and it is not known whether factors associated with an increased risk of RA also confer an increased risk of lymphoma. We investigated whether anti-cyclic citrullinated peptide (CCP) antibodies, other autoantibodies, and smoking, are associated with lymphoma development in RA.

METHOD: subclasses of anti-CCP antibodies and for 15 antinuclear antibody (ANA)-associated specific autoantibodies. Relative risks were estimated as crude and adjusted odds ratios (adjOR) with 95% confidence intervals (CIs) using logistic regression.

RESULTS: We found no association between anti-CCP IgG ≥ 25 units/mL (adjOR 1.4, 95% CI 0.7-2.7), anti-CCP IgG ≥ 500 units/mL (adjOR 1.4, 95% CI 0.7-3.0), anti-CCP Ig of other isotypes, other autoantibodies (adjOR any vs none 0.6, 95% CI 0.3-1.2), or cigarette smoking (adjOR ever vs never 1.1, 95% CI 0.5-2.2) and lymphoma risk among patients with RA.

CONCLUSION: , IgM, or IgA), nor other common autoantibodies, nor smoking predicted lymphoma risk in RA.

National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-342980 (URN)10.1080/03009742.2017.1376108 (DOI)29336646 (PubMedID)
Available from: 2018-02-24 Created: 2018-02-24 Last updated: 2018-03-08Bibliographically approved
Tjärnlund, A., Rönnelid, J., Bottai, M. & Lundberg, I. E. (2018). Response to: ‘Detection of myositis-specific antibodies’ by Vulsteke et al [Letter to the editor]. Annals of the Rheumatic Diseases
Open this publication in new window or tab >>Response to: ‘Detection of myositis-specific antibodies’ by Vulsteke et al
2018 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060Article in journal, Letter (Refereed) Epub ahead of print
Keywords
autoantibodies, disease activity, inflammation
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-343353 (URN)10.1136/annrheumdis-2018-212948 (DOI)29382639 (PubMedID)
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-02-28Bibliographically approved
Blom, K., ElShafie, A. I., Jönsson, U.-B., Rönnelid, J., Håkansson, L. & Venge, P. (2018). The genetically determined production of the alarmin eosinophil-derived neurotoxin is reduced in visceral leishmaniasis. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 126(1), 85-91
Open this publication in new window or tab >>The genetically determined production of the alarmin eosinophil-derived neurotoxin is reduced in visceral leishmaniasis
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2018 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 1, p. 85-91Article in journal (Refereed) Published
Abstract [en]

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis. Recent findings indicate that dendritic cells have a key role in the defense against the Leishmania parasite and that the activity of this cell may be modified by the eosinophil secretory protein eosinophil-derived neurotoxin (EDN). We hypothesized that the interactions between dendritic cells and EDN might be of importance in the disease development. Cellular content of EDN was analyzed by ELISA. The single-nucleotide polymorphisms at positions 405, 416, and 1122 in the EDN gene were analyzed by real-time PCR with TaqMan((R)) reagents. The study cohorts comprised 239 Sudanese subjects (65 healthy controls and 174 with VL) and 300 healthy Swedish controls. The eosinophil content of EDN was lower in VL as compared with controls (p < 0.0001). The EDN405 (G>C) genotype distribution was similar among Swedish and Sudanese controls, whereas VL subjects had a higher prevalence of the EDN405-GG genotype (p < 0.0001). The content of EDN in the eosinophils was closely linked to the EDN405 polymorphism (p = 0.0002). Our findings suggest that the predisposition to acquire VL is related to the genetic polymorphism of the EDN gene and the reduced production by the eosinophil of this gene product.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
Visceral leishmaniasis, kala-azar, eosinophil granulocyte, polymorphism, RNASE2
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-338960 (URN)10.1111/apm.12780 (DOI)000418846700011 ()29193305 (PubMedID)
Available from: 2018-01-18 Created: 2018-01-18 Last updated: 2018-02-27Bibliographically approved
Brink, M., Hansson, M., Mathsson Alm, L., Cornillet, M., Rönnelid, J., Skriner, K., . . . Rantapaa-Dahlqvist, S. (2017). Acpa Against Different Citrullinated Peptides Identify Specific Phenotypes Of Rheumatoid Arthritis. Paper presented at Annual European Congress of Rheumatology, JUN 14-17, 2017, Madrid, SPAIN. Annals of the Rheumatic Diseases, 76, 792-792
Open this publication in new window or tab >>Acpa Against Different Citrullinated Peptides Identify Specific Phenotypes Of Rheumatoid Arthritis
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2017 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, p. 792-792Article in journal, Meeting abstract (Other academic) Published
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-346632 (URN)10.1136/annrheumdis-2017-eular.5085 (DOI)000413181402360 ()
Conference
Annual European Congress of Rheumatology, JUN 14-17, 2017, Madrid, SPAIN
Available from: 2018-03-21 Created: 2018-03-21 Last updated: 2018-03-21Bibliographically approved
Manivel, V. A., Mullazehi, M., Padyukov, L., Westerlind, H., Klareskog, L., Alfredsson, L., . . . Rönnelid, J. (2017). Anti-Collagen Type Ii Antibodies Are Associated With An Acute Onset Rheumatoid Arthritis Phenotype And Prognosticate Lower Degree Of Inflammation. Paper presented at Annual European Congress of Rheumatology, JUN 14-17, 2017, Madrid, SPAIN. Annals of the Rheumatic Diseases, 76, 228-228
Open this publication in new window or tab >>Anti-Collagen Type Ii Antibodies Are Associated With An Acute Onset Rheumatoid Arthritis Phenotype And Prognosticate Lower Degree Of Inflammation
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2017 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, p. 228-228Article in journal, Meeting abstract (Other academic) Published
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-346626 (URN)10.1136/annrheumdis-2017-eular.2776 (DOI)000413181400613 ()
Conference
Annual European Congress of Rheumatology, JUN 14-17, 2017, Madrid, SPAIN
Available from: 2018-03-21 Created: 2018-03-21 Last updated: 2018-03-21Bibliographically approved
Manivel, V. A., Mullazehi, M., Padyukov, L., Westerlind, H., Klareskog, L., Alfredson, L., . . . Rönnelid, J. (2017). Anticollagen type II antibodies are associated with an acute onset rheumatoid arthritis phenotype and prognosticate lower degree of inflammation during 5 years follow-up. Annals of the Rheumatic Diseases, 76(9), 1529-1536
Open this publication in new window or tab >>Anticollagen type II antibodies are associated with an acute onset rheumatoid arthritis phenotype and prognosticate lower degree of inflammation during 5 years follow-up
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2017 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, no 9, p. 1529-1536Article in journal (Refereed) Published
Abstract [en]

Objective

Antifibrillar collagen type II (anti-CII) antibody-positive patients with rheumatoid arthritis (RA) have early but not late signs of increased inflammation and joint erosions. We wanted to replicate this in a large RA cohort, and to relate to human leukocyte antigen (HLA)-DRB1* alleles.

Methods

Anti-CII and anti-cyclic citrullinated peptide (CCP)2 were measured at baseline in 773 patients with RA from the Swedish Epidemiological Investigation in Rheumatoid Arthritis (EIRA) study with clinical follow-up data from the Swedish Rheumatology Quality Register (SRQ) registry, and 1476 with HLA-DRB1* information. Comparisons were done concerning C reactive protein (CRP), erythrocyte sedimentation rate (ESR), tender joint count (TJC), swollen joint count (SJC), Disease Activity Score encompassing 28 joints based on ESR (DAS28), DAS28CRP, pain-Visual Analogue Scale (VAS), global-VAS and Health Assessment Questionnaire Score (HAQ) at eight occasions during 5 years, and association with HLA-DRB1* alleles.

Results

Anti-CII associated with elevated CRP, ESR, SJC, DAS28 and DAS28CRP at diagnosis and up to 6 months, whereas anti-CCP2 associated with SJC and DAS28 from 6 months to 5 years, but not earlier. The anti-CII-associated phenotype was strong, and predominated in anti-CII/anti-CCP2 double-positive patients. Anti-CII was associated with improvements in CRP, ESR, SJC, TJC and DAS28, whereas anti-CCP2 was associated with deteriorations in SJC and DAS28 over time. Anti-CII-positive patients achieved European League Against Rheumatism good or moderate response more often than negative patients. Anti-CII was positively associated with HLA-DRB1*01 and HLA-DRB1*03, with significant interaction, and double-positive individuals had >14 times higher mean anti-CII levels than HLA double negatives. Whereas smoking was associated with elevated anti-CCP2 levels, smokers had lower anti-CII levels.

Conclusions

Anti-CII seropositive RA represents a distinct phenotype, in many respects representing the converse to the clinical, genetic and smoking associations described for anticitrullinated protein peptide autoantibodies. Although not diagnostically useful, early anti-CII determinations predict favourable inflammatory outcome in RA.

National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-311956 (URN)10.1136/annrheumdis-2016-210873 (DOI)000407833100022 ()28336519 (PubMedID)
Available from: 2017-01-03 Created: 2017-01-03 Last updated: 2018-02-27Bibliographically approved
Grönwall, C., Hardt, U., Gustafsson, J. T., Elvin, K., Jensen-Urstad, K., Kvarnstrom, M., . . . Svenungsson, E. (2017). Depressed serum IgM levels in SLE are restricted to defined subgroups. Clinical Immunology, 183, 304-315
Open this publication in new window or tab >>Depressed serum IgM levels in SLE are restricted to defined subgroups
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2017 (English)In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 183, p. 304-315Article in journal (Refereed) Published
Abstract [en]

Natural IgM autoantibodies have been proposed to convey protection from autoimmune pathogenesis. Herein, we investigated the IgM responses in 396 systemic lupus erythematosus (SLE) patients, divided into subgroups based on distinct autoantibody profiles. Depressed IgM levels were more common in SLE than in matched population controls. Strikingly, an autoreactivity profile defined by IgG anti-Ro/La was associated with reduced levels of specific natural IgM targeting phosphoiylcholine (PC) antigens and malondialdehyde (MDA) modified-protein, as well as total IgM, while no differences were detected in SLE patients with an autoreactivity profile defined by anti-cardiolipin/beta(2)glycoprotein-I. We also observed an association of reduced IgM levels with the HEA-DRB1*03 allelic variant among SLE patients and controls. Associations of low IgM anti-PC with cardiovascular disease were primarily found in patients without antiphospholipid antibodies. These studies further highlight the clinical relevance of depressed IgM. Our results suggest that low IgM levels in SLE patients reflect immunological and genetic differences between SLE subgroups.

Keywords
SLE, Natural IgM, Sjogren's syndrome, Antiphospholipid syndrome, IgM anti-PC, IgM anti-MDA, IgM anti-CWPS, SS, APS, Autoantibodies
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-341665 (URN)10.1016/j.clim.2017.09.013 (DOI)000414888600042 ()28919518 (PubMedID)
Funder
Swedish Research Council, E0395401 201303624Åke Wiberg Foundation, M16-0060Magnus Bergvall Foundation, 2014-00149 2015-00987Swedish Heart Lung Foundation, 20140436Stockholm County Council, 1311-1406The King Gustaf V's Jubilee Foundation, FAI2015-0187 FAI2014-0005Swedish Rheumatism Association, R-639601
Available from: 2018-02-14 Created: 2018-02-14 Last updated: 2018-02-27Bibliographically approved
Too, C. L., Murad, S., Hansson, M., Mathsson Alm, L., Dhaliwal, J. S., Holmdahl, R., . . . Padyukov, L. (2017). Differences in the Spectrum of Anti-Citrullinated Protein Antibody Fine Specificities Between Malaysian and Swedish Patients With Rheumatoid Arthritis: Implications for Disease Pathogenesis. Arthritis & Rheumatology, 69(1), 58-69
Open this publication in new window or tab >>Differences in the Spectrum of Anti-Citrullinated Protein Antibody Fine Specificities Between Malaysian and Swedish Patients With Rheumatoid Arthritis: Implications for Disease Pathogenesis
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2017 (English)In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69, no 1, p. 58-69Article in journal (Refereed) Published
Abstract [en]

Objective. Antibodies to the citrullinated protein antigens (ACPAs) are important in the diagnosis and pathogenesis of rheumatoid arthritis (RA). However, the prevalence of ACPAs with different fine specificities in different populations is unclear. This study sought to examine the fine specificity of the antibody responses toward citrullinated proteins in RA patients from Malaysia, an area where genetic and environmental determinants of RA are different from those in more frequently studied cohorts of Caucasian subjects. Methods. A multiplex analytic microarray system was used to analyze the occurrence of antibodies to 10 different citrullinated peptides (filaggrin [fil307-324], vimentin [Vim2-17, Vim60-75], fibrinogen [Fiba563-583, Fib alpha 580-600, Fib beta 36-52, Fib beta 62-81a, Fib beta 62-81b], enolase [Eno5-21], and type II collagen [CitCII355-378]) in serum samples from 4,089 RA patients (1,231 Malaysian and 2,858 Swedish) and 827 healthy control subjects (249 Malaysian and 578 Swedish). The positive reaction threshold for each peptide was set separately for each population based on a specificity of 98%. Results. Distinct differences in the frequencies of 5 ACPA fine specificities (Vim60-75, Vim2-17, Fibb62-81b, Eno5-21, and CitCII355-378) were found between the Malaysian and Swedish RA populations, despite a nearly identical percentage of patients in each population who were positive for anti-cyclic citrullinated peptide 2 ish RA patients, the frequencies of antibodies to Vim60-75 (54% versus 44%, corrected P [P-corr] =1.06 x 10(-8)) and CitCII355-378 (17% versus 13%, P-corr = 0.02) were significantly higher, while the frequencies of antibodies to Vim2-17 (25% versus 32%, P-corr = 1.91 x 10(-4)), Fib beta 62-81b (15% versus 30%, P-corr = 2.47 x 10(-22)), and Eno5-21 (23% versus 50%, P-corr = 3.64 x 10(-57)) were significantly lower. Conclusion. Serum ACPA fine specificities differ between RA patients in different populations, although the total proportions of individuals positive for ACPAs are similar. Differing patterns of ACPA fine specificity could be attributed to variations in genetic and/or environmental factors.

National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-316417 (URN)10.1002/art.39827 (DOI)000392505500008 ()27483449 (PubMedID)
Funder
Swedish Society of Medicine, DNR 348-2009-6468Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Foundation for Strategic Research Swedish Research Council
Available from: 2017-03-02 Created: 2017-03-02 Last updated: 2018-02-27Bibliographically approved
Sohrabian, A., Parodis, I., Carlströmer Berthen, N., Sjowall, C., Jonsen, A., Zickert, A., . . . Rönnelid, J. (2017). High Anti-Dsdna Content in Sle Immune Complexes is associated with Clinical Remission Following Belimumab Treatment. Paper presented at Annual European Congress of Rheumatology, JUN 14-17, 2017, Madrid, SPAIN. Annals of the Rheumatic Diseases, 76, 861-862
Open this publication in new window or tab >>High Anti-Dsdna Content in Sle Immune Complexes is associated with Clinical Remission Following Belimumab Treatment
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2017 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, p. 861-862Article in journal, Meeting abstract (Other academic) Published
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-346633 (URN)10.1136/annrheumdis-2017-eular.5054 (DOI)000413181402525 ()
Conference
Annual European Congress of Rheumatology, JUN 14-17, 2017, Madrid, SPAIN
Available from: 2018-03-21 Created: 2018-03-21 Last updated: 2018-03-21Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-1186-3226

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