In nonmalignant disease, there have been two mechanisms implicated in the association of HLA antigens with disease. In ankylosing spondylitis, evidence is accumulating for cross tolerance between a bacterial antigen and the HLA-B27 antigen; while in the autoimmune diseases, the involvement of an abnormal immune response gene, associated with A1/B8 haplotype, is strongly suspected. The same haplotype has also been associated with recovery from hepatitis B infection and survival of patients with Hodgkin's disease and acute myeloid leukaemia. At present, there are no techniques to study directly immune response genes in man and so these observations are still strictly academic. However, with increasing interest in the use of immunotherapy in cancer and the demonstration in mice that the major histocompatibility system may be the site of action of soluble mediators of immune memory, understanding the mechanisms of action of the HLA associated resistance factors may enable a more rational approach to immunotherapy in man.
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