The unique interplay between antinuclear antibodies and nuclear molecules in the pathogenesis of SLE

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that primarily affects young women and causes a wide range of inflammatory manifestations. The hallmark of SLE is the production of antibodies to components of the cell nucleus (antinuclear antibodies or ANAs). These antibodies can bind to DNA, RNA and protein complexes with nucleic acids. Among ANAs, antibodies to DNA (anti-DNA) are markers for classification and disease activity, waxing and waning in many patients. In the blood, anti-DNA antibodies can bind DNA to form immune complexes with two distinct roles in pathogenesis: renal deposition to provoke nephritis and stimulation of cytokine production following uptake into innate immune cells and interaction with internal nucleic acid sensors. These sensors are part of an internal host defense system in the cell cytoplasm that can respond to DNA from infecting organisms; during cell stress, DNA from nuclear and mitochondrial sources can also trigger these sensors. The formation of immune complexes requires a source of extracellular DNA in an immunologically accessible form. As shown inin vivo andin vitro systems, extracellular DNA can emerge from dead and dying cells in both a free and particulate form. Neutrophils undergoing the process of NETosis can release DNA in mesh-like structures called NETs (neutrophil extracellular traps). In SLE, therefore, the combination of ANAs and immunologically active DNA can create new structures which can promote inflam...
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Review Source Type: research