The role of somatic mutation in the pathogenic anti-DNA response

B Diamond, JB Katz, E Paul, C Aranow… - Annual review of …, 1992 - annualreviews.org
B Diamond, JB Katz, E Paul, C Aranow, D Lustgarten, MD Scharff
Annual review of immunology, 1992annualreviews.org
Anti-DNA antibodies represent a significant auto specificity in systemic lupus erythematosus
because they are essentially diagnostic of the disease and they contribute to renal
pathology. The molecular genetic characн terization of these antibodies from both lupus-
prone mice and humans with lupus has shown them to be somatically mutated. In many
cases the nature of the mutations suggests that DNA or some structurally homologous
molecule is driving the response. In other cases the high replacement-to-silent mutation ratio …
Abstract
Anti-DNA antibodies represent a significant auto specificity in systemic lupus erythematosus because they are essentially diagnostic of the disease and they contribute to renal pathology. The molecular genetic characн terization of these antibodies from both lupus-prone mice and humans with lupus has shown them to be somatically mutated. In many cases the nature of the mutations suggests that DNA or some structurally homologous molecule is driving the response. In other cases the high replacement-to-silent mutation ratio in framework regions of the antibody suggests selection by idiotype or by some mechanism other than antigen itself.
Current studies of immunoglobulin variable region genes encoding antiн DNA antibodies reveal no disease associated polymorphisms. There are also no data suggesting that the nature of the recombination process that forms intact variable region genes or of the process of somatic mutation differs in autoimmune and non autoimmune strains or kindred. Current data suggest, rather, that a defect in regulation is responsible for auto-
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