Major histocompatibility markers in disease

There are a number of common human diseases of unknown aetiology with possible precipitation by viral infection and, although strongly suspected of occurring only in genetically susceptible individuals, of unclear mode of inheritance. As a group, they are characterized by apparent 'autoimmunity' either against single cell types: pancreatic β-cells in insulin-dependent juvenile-onset diabetes mellitus (IDDM), the hepatocyte in chronic active hepatitis, or certain neurons in multiple sclerosis (MS); or against a number of organs, as in rheumatoid arthritis or systemic lupus erythematosus (SLE). Logically, they have been regarded as possibly being at least partly determined by postulated specific immune response genes in susceptible individuals. These considerations led to the search for HLA-disease associations, particularly among patients with this group of disorders. Such associations have been found. For the disease mentioned above, these associations are, in general, weak for HLA-A and HLA-B types and stronger for HLA-D and HLA-DR types. In contrast, other HLA- associated diseases without suspected immunopathogenesis are more markedly associated with HLA-A (haemochromatosis) or HLA-B (21-hydroxylase deficiency). In addition, a particular association has been found between HLA-B27 and ankylosing spondylitis. There is evidence for the association of certain immunoglobulin (Km and/or Gm) genetic markers with a high or low antibody response to flagellin to the polyribose phosphate antigen of Haemophilus influenzae or to pneumococcal C-polysaccharide and to the acetyl choline receptor in patients with myasthenia gravis.