Proposed mechanisms to explain the association of HLA-B27 with Reiter's syndrome (RS) and ankylosing spondylitis (AS) include abnormal immune response genes linked to HLA or a direct role for HLA antigens in disease pathogenesis. Our studies provide indirect evidence to support the latter hypothesis. Seventy-nine patients (44 with RS, 27 with AS and 8 with idiopathic sacroiliitis [SI]) were evaluated clinically and by HLA phenotyping. Of the 10 patients with RS who were B27-negative, 7 (70%) had another B locus antigen that was immunologically cross-reactive with B27 (B7-group antigen). These included B7 in two, BW22 in four, and BW42 in one. Four of eight patients with sacroiliitis alone had B27, but the remaining four all had B7. Two B27-negative AS patients had no B7-group antigens. Thus, 69% of B27-negative patients had cross-reactive HLA antigens.
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