Antibodies to DNA: infection or genetics?
- 30 October 2009
- journal article
- review article
- Published by SAGE Publications in Lupus
- Vol. 18 (13), 1176-1180
- https://doi.org/10.1177/0961203309106492
Abstract
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.Keywords
This publication has 26 references indexed in Scilit:
- Innate immune recognition of nucleic acidsImmunologic Research, 2008
- Autoreactive IgG memory antibodies in patients with systemic lupus erythematosus arise from nonreactive and polyreactive precursorsProceedings of the National Academy of Sciences of the United States of America, 2008
- Developments in the scientific understanding of lupusArthritis Research & Therapy, 2008
- DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune responseNature, 2007
- The type I interferon system in systemic lupus erythematosusArthritis & Rheumatism, 2006
- SLE—a disease of clearance deficiency?Rheumatology, 2005
- Induction of interferon‐α production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgGArthritis & Rheumatism, 2004
- Immune Activation by Bacterial DNA: A New Genetic CodeImmunity, 1996
- CpG motifs in bacterial DNA trigger direct B-cell activationNature, 1995
- Anti‐DNA Antibodies Induced by BK Virus InoculationsScandinavian Journal of Immunology, 1990