CURRENT CONCEPTS AND ADVANCES IN CLINICAL LABORATORY TESTING FOR AUTOIMMUNE-DISEASES

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-sp ecific autoimmune diseases are directed against antigens of the injure d organs, whereas the antinuclear antibodies (ANA) detected in systemi c 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 p resence or absence of specific ANA types will help predict the nature of the disease and the response to therapy. Noteworthy features of the se ''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 t o antihistone, (3) patients with mixed connective tissue disease have ANA restricted to anti-RNP, (4) patients with CREST (calcinosis, Rayna ud's, esophageal dysmotility, sclerodactyly, and telangiectasia) syndr ome have ANA restricted to anticentromere, (5) ANA with anti-SS-A/Ro s pecificity is associated with vasculitis and nephritis, (6) ANA with a nti-SS-B/La and anti-nRNP specificities is associated with milder clin ical disease, (7) ANAs with anti-Jo-1 and PM-Sd specificities are asso ciated with pulmonary fibrosis and poor prognosis. Technological advan ces in the fields of molecular immunogenetics are guiding the studies of autoimmune diseases from serological and histopathological evaluati ons toward search for subcellular risk factors such as chemical and bi ological agents and susceptibility genes. Knowledge of these factors w ill help (1) to identify disease susceptibility genes prior to clinica l onset and irreversible tissue damage, (2) to avoid environmental ris k factors, and (3) to devise specific immunosuppressive strategies.