Self-dsDNA in the pathogenesis of systemic lupus erythematosus

Abstract

SummarySystemic lupus erythematosus (SLE) is a systemic and poly-aetiological autoimmune disease characterized by the production of antibodies to autologous double-stranded DNA (dsDNA) which serve as diagnostic and prognostic markers. The defective clearance of apoptotic material, together with neutrophil extracellular traps (NETs), provides abundant chromatin or self-dsDNA to trigger the production of anti-dsDNA antibodies, although the mechanisms remain to be elucidated. In SLE patients, the immune complex (IC) of dsDNA and its autoantibodies trigger the robust type I interferon (IFN-I) production through intracellular DNA sensors, which drives the adaptive immune system to break down self-tolerance. In this review, we will discuss the potential resources of self-dsDNA, the mechanisms of self-dsDNA-mediated inflammation through various DNA sensors and its functions in SLE pathogenesis.

B cell–intrinsic TLR9 expression is protective in murine lupus

“…TLR9 could also be regulating TLR7-driven autoimmunity in trans, by promoting the production of protective anti-chromatin antibodies. This concept may seem to disagree with the consensus in the lupus field that anti-DNA and related autoantibodies are disease mediators (56,57). However, the current study and our prior work suggest that this may not always be the case.…”

The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: Recent findings and new perspectives

“…Systemic lupus erythematosus (SLE) is a systemic and poly-etiological autoimmune disease that is associated with a broad spectrum of clinical and immunologic manifestations. Early symptoms most frequently affect the skin and joints, whereas morbidity and mortality is mainly due to kidney damage (Bai et al, 2017;Yu et al, 2017). The development of nephritis in patients with SLE involves multiple pathways including aberrant apoptosis, autoantibody production, immune complex deposition, complement activation and inflammatory cytokines and interferon- production (Bai et al, 2017;Yu et al, 2017).…”

“…Additional typical renal features are glomerular crescents, podocyte injury, tubulointerstitial lesions and vascular injury. Although outcomes for patients with lupus nephritis have improved over the past 30 years, curative treatment of this disease still remains a challenge (Bai et al, 2017;Yu et al, 2017).…”

Quantitative changes innatural antibodies stimulated from a D-galactose-induced aging mouse model

“…Antibodies against anti-dsDNA play an important role in autoimmune disease, and are considered representative anti-nuclear autoantibodies in patients with systemic lupus erythematosus (SLE) [21]. Currently, the dsDNA antibody test is frequently used for early diagnosis of SLE [19].…”