The Pathogenesis of Lupus Nephritis

Abstract

Lupus nephritis is a serious potential feature of systemic lupus erythematous (SLE). Though SLE typically cycles through periods of flares and remission, patients often eventually succumb to end-stage kidney or cardiovascular damage. This review of the pathogenesis of lupus nephritis examines the role of the complement cascade; the significance of autoantibodies, the breaking of tolerance, and the implications of altered apoptosis in breaking tolerance; and the contributions of adaptive immunity and cross-talk with the innate immune system in driving renal damage. Delineation of basic mechanisms underlying the development of acute and chronic renal damage in lupus nephritis can result in the continued development of more specific and effective treatments.

Keywords: Immune complex; Kidney; Lupus; Mechanism; Nephritis.

Figure 1

Proposed mechanism of immune complex deposition of lupus nephritis.

Figure 2

Characteristic histopathologic manifestations of diffuse proliferative lupus nephritis (Class IV-G/A by the International Society of Nephrology/Renal Pathology Society Classification). Glomeruli (left column) are diffusely hyper-cellular. Peripheral capillary loop lumens are compromised due to endocapillary proliferation (arrow). Large immune complex deposits are observed between layers of basement membrane material (silver stain, middle, arrow) giving rise to the characteristic “tram track” or double contour appearance of the capillary loops. Immunofluorescence studies demonstrate the characteristic “full house” pattern of positive staining for all immune reactants (IgG, IgA, IgM, C1q, C3, kappa and lambda light chain) in glomeruli.