Evidence of concurrent immunopathological mechanisms determining the pathology of severe lupus nephritis

Abstract

The purpose of this study is to determine whether two distinct histopathological-immunopathological lesions, which have been reported in severe lupus nephritis, diffuse global glomerulonephritis (GN) (WHO IV) and a segmental and necrotising GN (WHO III) can be reported to coexist in a single patient. We examine the evidence of coexistence of these disparate lesions and the prognostic significance in a group of patients with severe lupus nephritis who have been subjected to a common therapeutic regimen by protocol. The simple, reproducible parameter indicating the presence of glomerular capillary necrosis was the presence of crescents. We, therefore, reviewed 39 renal biopsies with diffuse global lupus GN (WHO IV) (Churg, J, Sobin, LH. Lupus nephritis. Renal disease, classification and atlas of glomerular diseases. New York: Igaku-Shoin; 1982. p. 127-149). and used crescents as a surrogate for glomerular necrosis. Peripheral capillary immune deposits were less prominent in WHO IV with crescents compared with those without and resembled the reduced immune deposits seen in severe segmental GN (WHO III >or= 50%). Patients with WHO IV with crescents had decreased survival without end-stage renal disease (P = 0.02), fewer remissions (P = 0.04) and more adverse outcomes (12/22 vs 3/17) (P = 0.02) than those without crescents, and this was similar to patients with WHO III >or=50%. We conclude that, on the basis of immunological and morphological features, WHO IV with crescents appears to be the result of two distinct pathogenetic mechanisms. We propose that diffuse global lupus GN, associated with crescents, is best described as WHO class IV + WHO class III.

Long-term renal outcomes of childhood-onset global and segmental diffuse proliferative lupus nephritis

“…We observed similar amounts of fibrinoid necrosis/karyorrhexis and crescents in both subclasses, indicating that IV-G and IV-S were the combined result of immune complex-mediated glomerulonephritis and vasculitisinduced glomerular injury. Evidence of transformation between the two subclasses in repeat biopsies and the coexistence of both subclasses in a single glomerulus supports the concept that the pathogeneses underlying IV-G and IV-S could be related [25]. Distinct morphological features of IV-G and IV-S in children may reflect different stages of inflammatory glomerular injury within a single disease spectrum.…”

“…Growing evidence has supported the premise that the pathogenesis of DPLN is multifactorial [25]. Immune complex deposit-induced glomerular inflammation is a typical, wellrecognized pathogenesis, but may not be the sole mechanism [26].…”

Proliferative lesions and metalloproteinase activity in murine lupus nephritis mediated by type I interferons and macrophages

“…1A). This was of great interest because crescent formation in human membranoproliferative lupus nephritis is indicative of severe glomerular injury and associated with decreased survival and adverse outcomes (1)(2)(3). Poly (I:C)-treated mice displayed significantly higher histological glomerular and interstitial scores, with crescent formation in 60% of glomeruli; crescents were not observed in glomeruli from spontaneously proteinuric mice (Fig.…”

“…Mesangial and endothelial cell proliferation and leukocyte infiltration are frequent findings of active disease. Extracapillary epithelial cell proliferation, which leads to the formation of a cellular crescent, is a less-frequent finding in human lupus nephritis; however, it is characteristic of severe glomerular injury and an indicator of poor prognosis (1)(2)(3). The underlying mechanisms of crescent formation in lupus nephritis are largely unknown.…”

Significance of Histological Crescent Formation in Patients with Diffuse Proliferative Lupus Nephritis

“…There is evidence supporting the notion that there are at least two mechanisms leading to glomerular damage in severe proliferative LN: a pauci-immune-mediated process leading to the damage occurring in segmental lesions, and a peripheral capillary wall immune aggregate-mediated process in global lesions [21,22,23,24,25,26,27,28]. These reports have raised the possibility of a mechanism akin to pauci-immune necrotizing vasculitis for necrotizing and crescentic LN.…”