SLE is the prototype of human immune complex disease. Tissue damage in lupus is mainly caused by immune complexes containing autoantibodies to soluble antigens. These autoantibodies include antibodies against RNA-protein complexes (eg anti-Sm, RNP, Ro/SS-A, and La/SS-B antibodies) and DNA-protein complexes (eg amti-double-stranded DNA, antihistone, antichromatin antibodies). The largest antigens are found mainly in the cell nucleus, although in some cases (eg anti -ribosomal antibodies), they may be cytoplasmic. Immune complexes containing these autoantibodies, especially anti-dsDNA antibodies, are selectively enriched in the renal glomeruli (capillary tufts that produce urine as an ultrafiltrate of blood) of patients with lupus nephritis and are thought to play a critical role in establishing the inflammatory response. Immune complex deposition in the kidney leads to proliferative glomerulonephritis and effacement of the normal glomerular architecture. As in the case in serum sickness, active lupus nephritis is frequently associated with hypocomplementemia. In addition to the kidneys (glomeruli), immunoglobulin and complement deposits are found in the blood vessels (vasculitis), skin (rashes), nervous system, and other locations. Preformed immune complexes may become trapped in the glomemerular filter, or immune complexes may develop in situ because of the interaction of cationic antigens (eg histones) with heparan sulfate glycos-aminoglycan in the glomerular basement membrane. The association of lupus with deficiencies of the early classical complement components, especially C2 and C4, is consistent with the role of complement pathways in solubilizing immune complexes
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