Concepts of pathogenesis of systemic lupus erythematosus.
It is likely that different disease-inducing factors interfere with normal immune regulatory processes in different patients (1, 3). Some people may have such a strong genetic predisposition to disease that environmental insults may not be very important. Other individuals, with a much weaker genetic predisposition, may require strong environmental stimulation for disease induction (2). Defects in self-tolerance mechanisms could provide the genetic basis of disease or the target for environmental triggers. However, induction and perpetuation of pathogenic autoantibody production may frequently be a "multi-hit" process. The greater the number and/or degree of abnormalities (genetic and environmental), the greater the probability of disease.
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Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland 20892.
D000818:Animals; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB