TY - JOUR T1 - Immunogenetic Risks of Anti-Cyclical Citrullinated Peptide Antibodies in a North American Native Population with Rheumatoid Arthritis and Their First-degree Relatives JF - The Journal of Rheumatology JO - J Rheumatol SP - 1130 LP - 1135 DO - 10.3899/jrheum.080855 VL - 36 IS - 6 AU - HANI S. El-GABALAWY AU - DAVID B. ROBINSON AU - DONNA HART AU - BRENDA ELIAS AU - JANET MARKLAND AU - CHRISTINE A. PESCHKEN AU - IRENE SMOLIK AU - GABRIELA MONTES-ALDANA AU - MARLIS SCHROEDER AU - MARVIN J. FRITZLER AU - MARY CHEANG AU - KIEM OEN Y1 - 2009/06/01 UR - http://www.jrheum.org/content/36/6/1130.abstract N2 - Objective. To determine the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in unaffected relatives of North American Native probands with rheumatoid arthritis (RA); and the associations of the shared epitope (SE) and HLA-DRB1*0901 with RA and anti-CCP antibodies. Methods. The subjects were RA probands, affected relatives, unaffected first-degree (FDR) and more distant relatives, and unaffected controls from the same population. HLA-DRB1 typing was determined by DNA sequencing and anti-CCP antibodies were determined by ELISA. Results. DRB1*0901, SE, and SE/DRB1*0901 genotypes were all associated with RA. SE/DRB1*0901, but not other SE genotypes, was associated with disease onset at age < 16 years. The frequency of anti-CCP antibodies was 82% in RA probands, 17% in FDR, 11% in more distant relatives, and 3% in controls. Among unaffected relatives, a significant increased risk of anti-CCP was associated with SE/DRB1*0901 genotype, but not with SE. Conclusion. An independent association of the non-SE allele DRB1*0901 with RA was confirmed in this population, and this allele in combination with a SE allele was associated with younger age at disease onset. FDR of RA probands have a higher prevalence of anti-CCP antibodies than more distant relatives and unrelated controls, suggesting a gradient of risk for disease development. Immunogenetic risks may act early in disease pathogenesis at the level of initiation of RA autoantibody formation; however, it is not clear what additional genetic and environmental risks are involved in progression to clinical disease. ER -