Genetics and HLA antigens

Abstract

There is convincing evidence of a genetic basis for both psoriasis and psoriatic arthritis (PsA). Part of this genetic predisposition is due to genes within the major histocompatibility complex (MHC). In psoriasis, the primary association is with HLA-Cw6. Further work on specific nucleotide frequencies, especially those in the alpha 1 domain helix of the HLA-C molecule, will be of interest in determining whether a specific nucleotide frequency is present in all patients. The situation in PsA is considerably more complex. It is now established that there is an association between HLA-B27 and PsA, both in its peripheral arthropathy and in spinal disease in which radiological sacroiliitis is present. Spinal disease without radiological sacroiliitis is probably not associated with HLA-B27. There is some suggestion that HLA-B16 or its splits, HLA-B38 and HLA-B39, may also be associated with PsA, but there is considerable heterogeneity between the series, which prevents a firm conclusion being made. It is possible, but again not conclusive, that there is an association between HLA-DR4 and the symmetrical seronegative pattern of peripheral PsA. It is also likely that genes outwith the MHC predispose to psoriasis and PsA. It is further likely that a role will be found for environmental factors in both psoriasis and PsA. There is a tantalizing possibility of a complex interplay between a variety of environmental factors and genetic factors, both within and outwith the MHC, determining not only susceptibility but also the individual clinical pattern of disease. Further clarification of these possibilities is likely to depend primarily on understanding the role of genes within the MHC in predisposing to comparatively more homogeneous diseases, such as psoriasis and ankylosing spondylitis, before the mechanisms operating in PsA can be analysed and better understood.