Abstract
This review discusses the current concepts of immunological tolerance, physiological vs. pathological autoimmunity, autoimmune diseases, and laboratory tests helpful in diagnosis. The autoantibodies in organ-specific autoimmune diseases are directed against antigens of the injured organs, whereas the antinuclear antibodies (ANA) detected in systemic autoimmune diseases are detected against a vast array of nuclear and intracellular antigens and peptides necessary for DNA/RNA synthesis, repair, splicing, and transcription. Knowledge of the mean titer and presence or absence of specific ANA types will help predict the nature of the disease and the response to therapy. Noteworthy features of these “ANA profiles” are (1) patients with systemic lupus erythematosus frequently have multiple types of ANA but anti-dsDNA and anti-SM are diagnostic, (2) patients with drug-induced lupus have ANA restricted to antihistone, (3) patients with mixed connective tissue disease have ANA restricted to anti-RNP, (4) patients with CREST (calcinosis, Raynaud's, esophageal dysmotility, sclemdac-tyly, and telangiectasia) syndrome have ANA restricted to anticentromere, (5) ANA with anti-SS-A/Ro specificity is associated with vasculitis and nephritis, (6) ANA with anti-SS-B/La and anti-nRNP specificities is associated with milder clinical disease, (7) ANAs with anti-Jo-1 and PM-Scl specificities are associated with pulmonary fibrosis and poor prognosis.Technological advances in the fields of molecular immunogenetics are guiding the studies of autoimmune diseases from serological and histopathological evaluations toward search for subcellular risk factors such as chemical and biological agents and susceptibility genes. Knowledge of these factors will help (1) to identify disease susceptibility genes prior to clinical onset and irreversible tissue damage, (2) to avoid environmental risk factors, and (3) to devise specific immunosuppressive strategies.
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