HLA and the genesis of autoimmune diseases

In general, evidence of autoimmunity increase with age. The following explanations are proposed: Somatic mutations causing progressive changes in cell surfaces lead to progressive increase of antibodies which cross react with normal cell surfaces (auto-antibodies). The HLA antigens (and to a lesser extent other cell surface antigens) bind foreign molecules creating a hapten-carrier relationship which will direct the immune response to the surfaces of cells, which will most commonly be the blood and tissue leukocytes. However the HLA antigens on the surfaces of cells of some solid tissues may, for reasons intrinsic to the particular antigen and cell surface, bind haptenic material leading to an immune response directed in part against the tissue. This may be a short term event while the hapten is present, or it may continue in the absence of the hapten, directed at the carrier (cell surface) molecule alone. It may be perpetuated in some tissues (e.g. joint tissues) by the presence of immune complexes or other products of inflammation.