20 - Autoimmunity and Autoimmune Disease

Abstract

Autoimmunity is associated with disease. Autoimmune mechanisms underlie many diseases, some organ specific, others systemic in distribution. Autoimmune disorders can overlap. Genetic factors play a role in the development of autoimmune diseases. Twin studies show that there is a heritable component to autoimmunity. The majority of diseases are polygenic but HLA genes are particularly important. Self-reactive B and T cells persist even in normal subjects but in disease they are selected by autoantigen in the production of autoimmune responses. Controls on the development of autoimmunity can be bypassed. Microbial cross-reacting antigens and cytokine dysregulation can lead to autoimmunity. In most diseases associated with autoimmunity, the autoimmune process produces the lesions. This can be demonstrated in experimental models and human autoantibodies can be directly pathogenic. Immune complexes are associated with systemic autoimmune disease. Autoantibody tests are valuable for diagnosis, identification of disease subgroups and, in some diseases, for monitoring and prognosis. Treatment of autoimmune disease has a variety of aims. Treatment of organ-specific diseases usually involves metabolic control. Treatment of systemic diseases includes the use of anti-inflammatory and immunosuppressive drugs. Biological therapies, using monoclonal antibodies against pro-inflammatory cytokines and individual cell markers, have revolutionized the treatment of autoimmune rheumatic diseases. B-cell-directed therapies have proved highly effective in many autoimmune diseases.