Humoral Autoimmunity in Systemic Rheumatic Disease: A Review

'Antinuclear antibody' is a term now encompassing more than a dozen specificities, and cheap tests for these autoantibodies are readily available. Taken together with the clinical picture the tests can help in the fine tuning of diagnosis and perhaps prognosis within the connective tissue diseases. Certain anticellular antibodies appear to identify particular disease subsets and overlap syndromes, and their detection in conditions such as congenital heart block and recurrent abortion points to the presence there of autoimmune mechanisms. The antibody–disease relationships are reviewed here and the underlying mechanisms are explored. Associations between antibodies themselves and the paucity of evidence for direct pathogenetic effects in many cases leave open the possibility that antinuclear antibodies are clues to aetiology, reporters of a past event initiating both disease and autoantibody production. Retroviruses are candidates fast coming under scrutiny. Arcane though names such as Ro, La, Sm and Jo-1 may appear, much is now known about the intracellular targets of the antibodies; most are enzymes or particles active in DNA replication and the synthesis of RNA and protein. Hence, autoantibodies are useful tools for the molecular biologist as well as the clinician. New knowledge about autoantibodies may yield insights into the aetiology, as well as the pathogenesis, of systemic rheumatic diseases.