Despite intensive research over the past three decades, the events leading to pathogenic autoantibody production and immune deposit formation in individuals with systemic lupus erythematosus continues to be debated. The controversy is fueled by the clinical observations that individual patients with lupus have variable expression of disease, and that it is often difficult to completely distinguish the events involved in the initiation of nephritis from the processes leading to progressive disease and organ failure. This review focuses on the mechanisms of immune deposition in individuals with lupus nephritis. Recent evidence derived from both analysis of spontaneously occurring animal models of lupus nephritis and human lupus nephritis suggests that direct binding of autoantibodies to glomerular antigens is an important mechanism in lupus and other immune complex nephritides. In situ deposition of circulating autoantigens and autoantibodies also may play a role. These findings, taken together with observations from analysis of other autoimmune diseases, suggest that autoantigen ligation by autoantibodies may contribute to the inflammatory/fibrogenic response through either direct stimulation of cells or interruption of cell-cell or cell matrix interactions. The nature of these type of interactions in individual patients therefore may have disease- modulating effects. For example, the predominant autoantibody response likely influences the glomerular response to immune deposition and the ensuing inflammation. The evidence for, and implications of, this hypothesis are discussed.
|Original language||English (US)|
|Number of pages||9|
|Journal||Seminars in Nephrology|
|State||Published - Feb 1 1999|
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