Abstract | INTRODUCTION: METHODS: We created a bead-based, citrullinated antigen array to profile ACPAs. This custom array contains 16 citrullinated peptides and proteins detected in RA synovial tissues. We used the array to profile ACPAs in sera from a cohort of patients with RA and other non-inflammatory arthritides, as well as sera from an independent cohort of RA patients for whom data were available on carriage of HLA-DRB1 'shared epitope' (SE) alleles and history of cigarette smoking. RESULTS: Our multiplex assay showed that at least 10% of RA patients who tested negative in the commercial CCP assay possessed ACPAs. Carriage of HLA-DRB1 SE alleles and a history of cigarette smoking were associated with an increase in ACPA reactivity-in anti-CCP(+) RA and in a subset of anti-CCP(-) RA. CONCLUSIONS: Our multiplex assay can identify ACPA-positive RA patients missed by the commercial CCP assay, thus enabling greater diagnostic sensitivity. Further, our findings suggest that cigarette smoking and possession of HLA-DRB1 SE alleles contribute to the development of ACPAs in anti-CCP(-) RA.
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Authors | Catriona A Wagner, Jeremy Sokolove, Lauren J Lahey, Camilla Bengtsson, Saedis Saevarsdottir, Lars Alfredsson, Michelle Delanoy, Tamsin M Lindstrom, Roger P Walker, Reuven Bromberg, Piyanka E Chandra, Steven R Binder, Lars Klareskog, William H Robinson |
Journal | Annals of the rheumatic diseases
(Ann Rheum Dis)
Vol. 74
Issue 3
Pg. 579-86
(Mar 2015)
ISSN: 1468-2060 [Electronic] England |
PMID | 24297382
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. |
Chemical References |
- Autoantibodies
- Autoantigens
- Epitopes
- HLA-DRB1 Chains
- Peptides
- Peptides, Cyclic
- cyclic citrullinated peptide
- Citrulline
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Topics |
- Adolescent
- Adult
- Aged
- Alleles
- Arthritis, Psoriatic
(immunology)
- Arthritis, Rheumatoid
(immunology)
- Autoantibodies
(immunology)
- Autoantigens
(immunology)
- Case-Control Studies
- Citrulline
(immunology)
- Enzyme-Linked Immunosorbent Assay
- Epitopes
(genetics)
- Female
- Gout
(immunology)
- HLA-DRB1 Chains
(genetics)
- Humans
- Lupus Erythematosus, Systemic
(immunology)
- Male
- Middle Aged
- Peptides
(immunology)
- Peptides, Cyclic
(immunology)
- Smoking
(immunology)
- Young Adult
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