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HLA-DRB1 Haplotypes and RA Disease Outcomes

J Rheumatol; ePub 2019 Mar 1; Zhao, Mauer, et al

HLA-DRB1 haplotypes are independently and variably associated with seropositivity, autoantibody concentrations, and outcomes in rheumatoid arthritis (RA), according to a recent study. 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 follow-up. 16 HLA-DRB1 haplotypes and shared epitope (SE) status were determined from banked DNA. Researchers found:

  • Within VARA, 1,443 participants had genotyping and accrued 6,150 patient-years of follow-up.
  • 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.
  • Haplotypes SKA was associated with higher mortality.

Zhao M, Mauer L, Sayles H, et al. HLA-DRB1 haplotypes, shared epitope, and disease outcomes in US veterans with rheumatoid arthritis. [Published online ahead of print March 1, 2019]. J Rheumatol. doi:10.3899/jrheum.180724.