| Very high level of anti-citrullinated peptide antibodies associate with HLA-DRB1*15 non-shared epitope allele in patients with rheumatoid arthritis. | |
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MedLine Citation:
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PMID: 22307773 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Objective: Production of anti-citrullinated peptide antibodies (ACPA) is an important biomarker for rheumatoid arthritis (RA). Our goal was to determine whether genetic factors (HLA-DRB1 alleles) are associated with extreme ACPA level in individuals with ACPA positive RA and whether there are any phenotypic characteristics associated with these subgroups of RA. Methods: HLA-DRB1 allelic groups were genotyped in 1073 ACPA positive RA patients from the Swedish EIRA study. We found that 283 patients (26.4%) had high ACPA level (defined as >1,500 units using the Eurodiagnostica anti-CCP2 test), while the rest of patients had moderate ACPA level and served as the comparison group. A replication group consisted of 232 RA patients. Results: No significant differences in baseline disease activity between patients with high and moderate ACPA level were observed. However, the DRB1*15 allele was associated with high ACPA level (p=0.0002). Similar trend was detected in DRB1*15 positive patients replication cohort with overall effect in meta analysis towards developing of high ACPA in both studies (p<0.0001 in Mantel-Haenzel test, non-random effects). Conclusion: Our data indicate that HLA-DRB1*15 may promote the production of high ACPA level. Due to high value of ACPA level scores in the 2010 ACR/EULAR classification criteria of RA, the presence of HLA-DRB1*15 may, at least in part, contribute to fulfilling the criteria of RA. This illustrates the complex nature of the genetic regulation of ACPA level. Additional mechanistic studies on the regulation of ACPA and ACPA-positive RA are pending. |
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Authors:
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Judit Laki; Emeli Lundström; Omri Snir; Johan Rönnelid; Izabella Ganji; Anca I Catrina; Camilla Bengtsson; Saedis Saevarsdottir; Marius C Wick; Lars Alfredsson; Lars Klareskog; Leonid Padyukov |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-3 |
Journal Detail:
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Title: Arthritis and rheumatism Volume: - ISSN: 1529-0131 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 by the American College of Rheumatology. |
Affiliation:
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Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Rheumatology, National Health Centre, Budapest, Hungary. laki_jutka@yahoo.com. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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