Both glomerulonephritis and tubulointerstitial disease in SLE are mediated by the formation of immune complex (IC) deposits in glomeruli or on tubular basement membranes. Glomerular deposits occur at mesangial, subendothelial, and subepithelial sites. Mesangial and subendothelial IC deposits may result from glomerular trapping of circulating ICs but this process has not been clearly shown to cause glomerulonephritis. The amount of circulating IC trapping by the glomerulus is determined by characteristics of the IC itself, systemic factors, and several intrinsic properties of the glomerulus. IC deposits may also form in situ at mesangial, subendothelial, and subepithelial sites, and glomerular injury is produced by this mechanism at each of these sites. In situ deposit formation is favored by the presence of free antigen and antibody in the circulation. In the subepithelial space it occurs most rapidly when antigen and antibody are positively charged. Serologic data in membranous SLE in man are consistent with these conditions. The dynamic equilibrium which exists in IC disease is such that elevated circulating IC levels, which may be aggravated by factors such as mononuclear phagocyte system blockade, also favor antigen:antibody dissociation and tissue injury due to in situ IC formation. Thus, circulating IC levels may correlate with disease activity, although the circulating ICs themselves may not be the initiators of tissue injury. Based on recent studies in acute serum sickness the mechanism by which IC formation mediates the proliferative forms of SLE may involve a greater role for macrophages than for complement of neutrophils. Experimental membranous nephropathy is a complement-dependent, neutrophil-independent process. The role of sensitized and natural killer cells in glomerulonephritis is unresolved. Tubulointerstitial nephritis results from IC formation in peritubular capillaries and on tubular basement membranes which may be induced by renal or extra-renal antigens. Most such tubular ICs probably also form in situ and mediate tissue injury by mechanisms that include complement, neutrophils, and both sensitized and natural killer cells.
|Original language||English (US)|
|Number of pages||9|
|Journal||American Journal of Kidney Diseases|
|Issue number||1 Suppl. 1|
|State||Published - Dec 1 1982|
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