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Non inherited maternal HLA antigens in susceptibility to familial rheumatoid arthritis
  1. Katherine A. Guthrie (kguthrie{at}fhcrc.org)
  1. Fred Hutchinson Cancer Research Center, United States
    1. Natalia R Tishkevich (ntishkev{at}u.washington.edu)
    1. University of Washington, United States
      1. J Lee Nelson (lnelson{at}fhcrc.org)
      1. Fred Hutchinson Cancer Research Center, United States

        Abstract

        Objectives: Some rheumatoid arthritis (RA) patients lack RA-associated HLA alleles. Prior studies investigated non-inherited maternal HLA alleles (NIMA) in RA risk with conflicting results.

        Methods: We examined NIMA in a large cohort of families from the North American Rheumatoid Arthritis Consortium.

        Results Among 620 patients with one or both parents HLA-genotyped, RA patients informative for analysis included 176 without HLA-DRB1*04 and 86 without the HLA shared epitope (SE). The frequency of NIMA encoding HLA-DR4 or the SE was compared to the non-inherited paternal allele (NIPA). DR4-encoding NIMA vs. NIPA revealed no significant difference (27% vs. 20%). However, parity is known to modulate RA risk and analyses stratified by sex and age of onset showed significant variation among women. Interestingly, among women with onset <45 years DR4-encoding NIMA was increased compared to NIPA; among women >45 years at onset the reverse was observed (31% vs. 16% compared to 10% vs. 60%, p=0.008). DR4 encoding NIMA vs. NIPA did not differ in men. The SE did not differ in men or women.

        Conclusions: Risk of RA was associated with HLA-DR4 encoding NIMA in younger-onset women but not in older-onset women or men. These observations could help explain conflicting prior results of NIMA in RA.

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