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Antibodies to carba...
Antibodies to carbamylated alpha-enolase epitopes in rheumatoid arthritis also bind citrullinated epitopes and are largely indistinct from anti-citrullinated protein antibodies
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- Reed, Evan (författare)
- Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
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- Jiang, Xia (författare)
- Karolinska Institutet
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- Kharlamova, Nastya (författare)
- Karolinska Institutet
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- Ytterberg, A. Jimmy (författare)
- Karolinska Institutet
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- Catrina, Anca I. (författare)
- Karolinska Institutet
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- Israelsson, Lena (författare)
- Karolinska Institutet
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- Mathsson-Alm, Linda (författare)
- Uppsala universitet,Klinisk immunologi,ThermoFisher Sci, Uppsala, Sweden.
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- Hansson, Monika (författare)
- Karolinska Institutet
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- Alfredsson, Lars (författare)
- Karolinska Institutet
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- Rönnelid, Johan (författare)
- Uppsala universitet,Klinisk immunologi
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- Lundberg, Karin (författare)
- Karolinska Institutet
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Karolinska Institutet Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden (creator_code:org_t)
- 2016-05-04
- 2016
- Engelska.
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362. ; 18
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: In addition to anti-citrullinated protein antibodies (ACPAs), antibodies targeting carbamylated (i.e., homocitrullinated) proteins (anti-CarP antibodies) have been described in rheumatoid arthritis (RA). However, the extent to which anti-CarP antibodies are truly distinct from ACPA remains unclear, and few studies have focused on specific autoantigens. Here, we examine cross-reactivity between ACPA and anti-CarP antibodies, in the context of the candidate autoantigen a-enolase. Methods: Cross-reactivity was examined by immunoblotting of citrullinated and carbamylated proteins using purified ACPA; and by peptide absorption experiments, using the citrullinated alpha-enolase peptide CEP-1 and a homocitrulline-containing version (carb-CEP-1) in ELISA. The population-based case-control cohort EIRA (n = 2836 RA; 373 controls) was screened for reactivity with CEP-1 and carb-CEP-1, using the ISAC multiplex array. Associations between anti-CarP antibodies, smoking and genetic risk factors were analysed using unconditional logistic regression models. Differences in antibody levels were investigated using the Mann-Whitney U test. Results: Affinity-purified ACPA was found to bind carbamylated proteins and homocitrulline-containing peptides, demonstrating definitive cross-reactivity between ACPA and anti-CarP antibodies. Anti-carb-CEP-1 reactivity in EIRA was almost exclusively confined to the CEP-1-positive subset, and this group of RA patients (21 %) displayed a particularly strong ACPA response with marked epitope spreading. The small RA subset (3 %) with homocitrulline reactivity in the absence of citrulline reactivity did not associate with smoking or risk genes, and importantly had significantly lower anti-carb-CEP-1 antibody levels. Conclusion: Our data presented herein cast doubt on the specificity of anti-CarP antibodies in RA, which we posit may be a subset of cross-reactive ACPA.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- Anti-citrullinated protein antibodies
- Anti-carbamylated protein antibodies
- Rheumatoid arthritis
- Cross-reactivity
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Reed, Evan
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Jiang, Xia
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Kharlamova, Nast ...
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Ytterberg, A. Ji ...
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Catrina, Anca I.
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Israelsson, Lena
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visa fler...
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Mathsson-Alm, Li ...
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Hansson, Monika
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Alfredsson, Lars
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Rönnelid, Johan
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Lundberg, Karin
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Reumatologi och ...
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Arthritis Resear ...
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Uppsala universitet
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Karolinska Institutet