TY - JOUR T1 - HLA-DRB1 Haplotypes, Shared Epitope, and Disease Outcomes in US Veterans with Rheumatoid Arthritis JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.180724 SP - jrheum.180724 AU - Ming Zhao AU - Lilli Mauer AU - Harlan Sayles AU - Grant W. Cannon AU - Andreas Reimold AU - Gail S. Kerr AU - Joshua F. Baker AU - Geoffrey M. Thiele AU - Bryant R. England AU - Ted R. Mikuls Y1 - 2019/03/01 UR - http://www.jrheum.org/content/early/2019/02/25/jrheum.180724.abstract N2 - Objective To evaluate associations of HLA-DRB1 haplotypes and shared epitope (SE) with rheumatoid arthritis (RA) severity and all-cause mortality in RA. Methods Patients with RA from the Veterans Affairs Rheumatoid Arthritis (VARA) registry were followed from enrollment until death or December 31, 2013. Clinical characteristics, DNA, and serum were collected at enrollment. Radiographic damage, the presence or absence of subcutaneous nodules, disease activity measures, and functional status were assessed at enrollment and updated during followup. Sixteen HLA-DRB1 haplotypes and SE status were determined from banked DNA. Associations between HLA-DRB1 haplotypes, RA disease characteristics, and mortality were assessed in multivariable regression models. Results Within VARA, 1443 participants had genotyping and accrued 6150 patient-years of followup. Haplotypes VKA, VRA, LRA, SRA, SRE, SKR, and SEA, and SE alleles were significantly associated with seropositivity for rheumatoid factor (RF) and/or anticyclic citrullinated peptide (anti-CCP). Haplotypes VKA and SKR were associated with higher RF concentrations, while VRA, DRE, and GRQ were associated with lower RF concentrations. Haplotypes VKA, VRA, and LRA were associated with higher concentrations of anti-CCP antibody, while haplotypes SRA, SRE, LEA, SKR, and SEA were significantly associated with lower anti-CCP concentrations. Haplotype VKA (OR 1.39, 95% CI 1.08–1.80) was associated with increased frequency of radiographic damage at enrollment but none of the haplotypes were associated with the presence of subcutaneous nodules. Haplotypes SKA (HR 1.52, 95% CI 1.26 –1.83) was associated with higher mortality. Conclusion HLA-DRB1 haplotypes are independently and variably associated with seropositivity, autoantibody concentrations, and outcomes in RA. ER -