Factors Involved in the Pathogenesis of HLA-B27 Associated Arthritis

Abstract

The role of HLA-B27 in the pathogenesis of ankylosing spondylitis (AS), reactive arthritides (ReA) like Reiter's syndrome (RS) and acute anterior uveitis in unknown. The prevalence of these diseases in B27 positive individuals is five times greater than in the general population. In B27 positive relatives of such patients the prevalence is another ten times greater. In those being HLA-B27/HLA-B60 the prevalence increases again three times. Outside B27 and B60 no other responsible genetic markers have been found, although other factors must play a role to explain the familial preponderance. Since there are no indications that familial exogenous factors are of importance. these are probably genetic.

None of the seven subtypes of B27 seems to show a prevalence for these diseases although more studies are urgently needed. This means that probably the so called B pocket in the groove of HLA-B27 molecules, fixing the arginine at position 2 of the peptides which are presented to the receptors of cytotoxic T cells is of pathogenic importance.

It is possible that such peptides are derived from or induced by intracellularly proliferating Gram negative bacteria. Indicating these peptides already as arthritogenic and/or uveitogenic is probably too simple.

It seems probable that the pathogenetic role of HLA-B27 is that of a common pathway bridging various exogenous factors with several clinical pictures (Figure 1). AAU is mostly unilateral and not always attacking the same eye. Also in B27 associated joint diseases some joints are affected and others not. It is possible that local fluctuations in cytokine levels, e.g. TGF-β, are responsible for the onset of inflammatory processes in organs where normally maaophages are already active.