Rheumatic Disease Clinics of North America

Ankylosing Spondylitis and related spondyloarthropathies form a family of rheumatic diseases that are characterized by inflammatory peripheral and axial arthritis, with predilection for sacroiliitis, and a remarkably strong association with a genetic marker, HLA-B27. The association with B27 has provided a great impetus to the epidemio-logic studies of spondyloarthropathies and also helped broaden the clinical spectrum of these diseases. There are at least six Subtypes of B27, and the x-ray crystallographic structure of the common B27 subtype (B*2705) is now known. Endogenous peptides bound in the B27 antigen-binding cleft have been isolated and all seem to be nonamers (i.e., nine amino acids long). The close association of HLA-B27 with arthritic conditions has led to the Suggestion that these diseases are mediated by cytotoxic T lym-phocytes that recognize self-peptides presented by HLA-B27 molecules. The further association with enteric bacterial infections suggests that bacterial antigens may prime the CTL that later crossreacts on seif. Bacterial infections do not usually generate CTL responses. We speculate here that unusual properties of HLA-B27 molecules may predispose to such responses. Thus, HLA-B27-related disease may be an unfortunate consequence of the generation of a suitable, self-mimicking HLA-B27-binding peptide by certain bacteria, plus an unusual propensity for the HLA-B27 molecule to bind and present such peptides. In recent studies, ileocolonoscopy has revealed ileal or colonic in-flammatory changes in 30% to 60% of patients with spondyloar-thropathies. In patients with a short duration of arthritis, the changes are similar to those observed in patients with bacterial en-teritis. In those with prolonged or chronic spondyloarthropathy, the changes show chronic inflammation, with features of Crohn's disease in a quarter of the patients. It is tempting to speculate that infection leads to chronic gut inflammation with increased absorption of bacterial products that may contribute to the development of arthritis and Spondylitis. The microbes probably do not persist in the host in a dividing form, because contrary to patients with chla-mydia-triggered reactive arthritis, the prolonged use of antimicrobial chemotherapy in patients with acute enteroarthritis does not influence the natural course of the arthritis. The use of sulf asalazine in the rreatment of spondyloarthropathies seems to be promising. Acute enteric infections caused by Yersiniae, Salmonellae, Shigellae, and Campylobacters are sometimes, especially in HLA-B27-positive persons, followed by development of reactive arthritis. The role of bacterial antigens in the pathogenesis of this complication is discussed in this article. Several differences in immune responses against causative agents between …