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The HLA system, autoimmune endocrinopathy and diabetes mellitus

The basic features of the HLA system have been reviewed in a recent issue of the British Medical Bulletin (September 1978) and its interest lies in providing understanding of the effects of complex genetic interactions on basic biological functions which have major implications in clinical medicine. In recent years, a great deal of attention has been focussed on both the H2 system in the mouse and the homologous HLA chromosomal region in man which forms approximately one thousandth of the total human genome. The functional and evolutionary significance of the HLA system has been elegantly reviewed [ l ] . Interest first developed directly from the observations that histocompatibility antigens influence the survival of tissue grafts both in animals and in man. In addition, studies in the mouse have defined certain regions within the H2 system which contain genes controlling specific immune responses, genes which control complement factors and immune associated antigens and genes which determine mixed lymphocyte culture reactions [2]. The realization that similar genes probably exist within the HLA system in man has led to an unparalleled collaborative effort between immunologists and clinicians to elucidate the pathogenic mechanisms which may be involved in the destruction of different tissues and organ systems [3]. Many diseases which show an association with the HLA system have several characteristic common features. For example, an underlying genetic determination is seen by the familial aggregation of the same or other closely related diseases. In many instances the mode of genetic transmission has already been extensively explored leading to a variety of widely differing conclusions ranging from single gene inheritance to polygenic or multifactorial inheritance. The classic example of this is diabetes mellitus. However, the important lesson here is that the clinical syndrome of diabetes reflects several different disease processes. A similar argument applies to a number of other conditions which have a complex association with the HLA system such as myasthenia gravis, pernicious anaemia and Hashimoto’s thyroiditis. The low frequency of some HLA associated autoimmune diseases (eg. systemic lupus erythematosus) in families underlines the importance of the environmental triggering factor(s) which may be relatively uncommon, or require interaction with other agents to initiate the immune mediated destructive process. The circumstantial evidence, mainly epidemiological in origin, for invoking viruses as the probable environmental agent in several of