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Presence of autoant...
Presence of autoantibodies in "seronegative" rheumatoid arthritis associates with classical risk factors and high disease activity
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- Reed, Evan (author)
- Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, CMM L8 04, S-17176 Stockholm, Sweden.
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- Hedstrom, Anna Karin (author)
- Karolinska Institutet
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- Hansson, Monika (author)
- Karolinska Institutet
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- Mathsson Alm, Linda (author)
- Uppsala universitet,Klinisk immunologi,Thermo Fisher Sci, Uppsala, Sweden.
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- Brynedal, Boel (author)
- Karolinska Institutet
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- Saevarsdottir, Saedis (author)
- Karolinska Institutet
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- Cornillet, Martin (author)
- Univ Toulouse, Unite Differenciat Epitheliale & Autoimmunite Rhu, INSERM, UMR 1056, Toulouse, France.
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- Jakobsson, Per-Johan (author)
- Karolinska Institutet
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- Holmdahl, Rikard (author)
- Karolinska Institutet
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- Skriner, Karl (author)
- Charite, Dept Rheumatol & Clin Immunol, Berlin, Germany.
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- Serre, Guy (author)
- Univ Toulouse, Unite Differenciat Epitheliale & Autoimmunite Rhu, INSERM, UMR 1056, Toulouse, France.
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- Alfredsson, Lars (author)
- Karolinska Institutet
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- Rönnelid, Johan (author)
- Uppsala universitet,Klinisk immunologi
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- Lundberg, Karin (author)
- Karolinska Institutet
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Karolinska Institutet Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, CMM L8 04, S-17176 Stockholm, Sweden (creator_code:org_t)
- 2020-07-16
- 2020
- English.
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In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362. ; 22:1
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Abstract
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- BackgroundRheumatoid arthritis (RA) is classified as seropositive or seronegative, depending on the presence/absence of rheumatoid factor (RF), primarily IgM RF, and/or anti-citrullinated protein antibodies (ACPA), commonly detected using anti-cyclic citrullinated peptide (CCP) assays. Known risk factors associate with the more severe seropositive form of RA; less is known about seronegative RA. Here, we examine risk factors and clinical phenotypes in relation to presence of autoantibodies in the RA subset that is traditionally defined as seronegative.MethodsAnti-CCP2 IgG, 19 ACPA fine-specificities, IgM/IgG/IgA RF, anti-carbamylated-protein (CarP) antibodies, and 17 other autoantibodies, were analysed in 2755 RA patients and 370 controls. Antibody prevalence, levels, and co-occurrence were examined, and associations with risk factors and disease activity during 5 years were investigated for different antibody-defined RA subsets.ResultsAutoantibodies were detected in a substantial proportion of the traditionally defined seronegative RA subset, with ACPA fine-specificities found in 30%, IgA/IgG RF in 9.4%, and anti-CarP antibodies in 16%, with a 9.6% co-occurrence of at least two types of RA-associated autoantibodies. HLA-DRB1 shared epitope (SE) associated with the presence of ACPA in anti-CCP2-negative RA; in anti-CCP2-positive RA, the SE association was defined by six ACPA fine-specificities with high co-occurrence. Smoking associated with RF, but not with ACPA, in anti-CCP2-negative RA. Presence of ACPA and RF, but not anti-CarP antibodies, in conventionally defined “seronegative” RA, associated with worse clinical outcome.Conclusions“Seronegative” RA is not truly a seronegative disease subset. Additional screening for ACPA fine-specificities and IgA/IgG RF defines a group of patients that resembles seropositive patients with respect to risk factors and clinical picture and may contribute to earlier diagnosis for a subset of anti-CCP2−/IgM RF− patients with a high need for active treatment.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- Rheumatoid arthritis (RA)
- Autoantibodies
- Anti-citrullinated protein antibodies (ACPA)
- Cyclic citrullinated peptide (CCP)
- Rheumatoid factor (RF)
- Anti-carbamylated protein antibodies (anti-CarP)
- Disease activity score for 28 joints (DAS28)
- HLA-DRB1 shared epitope (SE)
- Smoking
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Reed, Evan
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Hedstrom, Anna K ...
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Hansson, Monika
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Mathsson Alm, Li ...
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Brynedal, Boel
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Saevarsdottir, S ...
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Cornillet, Marti ...
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Jakobsson, Per-J ...
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Holmdahl, Rikard
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Skriner, Karl
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Serre, Guy
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Alfredsson, Lars
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Rönnelid, Johan
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Lundberg, Karin
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Rheumatology and ...
- Articles in the publication
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Arthritis Resear ...
- By the university
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Uppsala University
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Karolinska Institutet