Antinuclear antibodies: diagnostic markers and clues to the basis of systemic autoimmunity

Systemic autoimmune diseases include systemic lupus erythematosus (SLE), scleroderma, Sjögren's syndrome and dermato-polymyositis among others. These diseases are characterized by the occurrence of autoantibodies directed against nuclear antigens. Each disease is associated with a distinctive group of autoantibodies which can be used as diagnostic markers or reagents to separate one disease from another. Examples include antibodies to native DNA and to Sm antigen which are distinctive for SLE, antibodies to DNA topoisomerase I, centromere antigens and RNA polymerase I which are distinctive for scleroderma and antibodies to transfer RNA synthetases which are distinctive for dermato-polymyositis. In a sense these can be regarded as immune fingerprints which are characteristic of these disease entities and they have therefore been useful to the clinician as aids to differential diagnosis. Some insight into the nature of systemic autoimmunity has come from studies defining the molecular biology of antigens in SLE and scleroderma. In SLE some of the antigens such as Sm and U1-ribonucleoprotein are assembled as small nuclear ribonucleoprotein particles which are involved in splicing of precursor messenger RNA, thus being involved in an important and essential cellular function. In scleroderma it has been shown that antigens such as DNA topo I, centromere and RNA pol I can also be demonstrated to be co-localized in close proximity at a certain point in cell division. These observations are very compelling for the hypothesis that the immunogen(s) in systemic autoimmunity might be intracellular particles composed of assemblies of protein and nucleic acids of various kinds.(ABSTRACT TRUNCATED AT 250 WORDS)