Antibodies to DNA: infection or genetics?
Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus (SLE) and unique markers of the immunological disturbances critical to disease pathogenesis. In the form of immune complexes, anti-DNA autoantibodies can deposit in the tissue to incite inflammation and damage; in addition, these complexes can induce cytokine production, most prominently, type 1 interferon. Studies in both patients and animal models have implicated genetic as well as environmental factors in the aetiology of the anti-DNA response. Because bacterial DNA is a potent stimulant of innate immunity by both toll-like receptor (TLR) and non-TLR signalling pathways, foreign DNA introduced during the course of bacterial or viral infection could have a dual role in antibody induction. This DNA could serve as an adjuvant to activate innate immunity as well as an immunogen to drive an antigen-specific antibody response. In this scenario, the generation of cross-reactive autoantibodies, in contrast to highly specific antibodies to bacterial DNA, most likely depends on genetically determined abnormalities in the B-cell repertoire in patients with SLE. Given the universal expression of DNA, this model suggests that many different kinds of infections could trigger pathogenic autoantibody responses in SLE, as well as induce flare.
Pisetsky
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DS
Division of Rheumatology and Immunology, Duke University Medical Center, Durham, North Carolina 27705, USA. piset001@mc.duke.edu
Vrabie
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IA
D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D004247:DNA / Q000276:immunology*; D004269:DNA, Bacterial / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007239:Infections / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D004269:DNA, Bacterial; D051193:Toll-Like Receptors; D004247:DNA