B27 positive diseases versus B27 negative diseases

Abstract

Of all the known associations between HLA and diseases, the association of B27 with ankylosing spondylitis (AS) is the strongest. The B27 antigen is present in over 90% of patients with AS as compared with the B27 prevalence of 8% in Caucasians in general. A strong but slightly minor association has also been found between B27 and Reiter's syndrome (RS), reactive arthritis (ReA), and acute anterior uveitis (AAU). These diseases are so strongly interrelated, especially in the presence of B27, that one may speak of 'B27 associated diseases'. Many authors regard psoriatic arthritis, also, as a disease associated with B27. For reasons which will be discussed below, however, we consider B27 to be associated mainly with the spondylitic part of psoriatic arthritis and not with psoriatic arthritis in general, as others have suggested. The aetiology of these diseases remains elusive. Interaction of environmental and genetic factors have been postulated; nevertheless, a decade after the landmark results on HLA-B27 and its associated diseases the nature of the mechanisms underlying these associations is still subject to much speculation. The association of B27 with its associated diseases is far from complete. This could be explained if, besides B27, other genes near the B locus on chromosome 6, or on other chromosomes, were involved in the pathogenesis. From epidemiological and family studies other genetic factors have also emanated to explain the observed incomplete association. None of the studies of genetic factors in the pathogenesis of AS, however, clearly indicated genes other than B27. Nor did any of the B27 subtypes show a particular association with AS. Strong evidence for B27 as the major genetic susceptibility factor is found in detailed population and family studies, in which no stronger association has been observed other than that between B27 and AS. A stronger B27 association has been found in Caucasians with spondylitis than in their American black counterparts. In addition to genetic factors, infectious agents have been regarded as a likely cause of primary AS. Several studies by Ebringer et al strongly suggested Klebsiella pneumoniae in this respect, but other authors could not confirm their results. In reactive arthritis clear cut evidence for causative infectious organisms of urinary and enteric origin have been demonstrated. In the cases where HLA-B27 is considered to play a part in the pathogenesis of B27 associated diseases, B27-AS, B27-RS, B27-ReA, and B27-AAU are probably the same diseases, but developing along different lines. We have attempted to solve this problem by comparing the clinical pictures of B27+AS, B27+RS, B27+ReA, and B27+AAU with those of their B27- counterparts. A review of the literature is given together with the observations made by our own group.