Thrombozytenfunktion und Thrombozyten-assoziierte Immunglobuline bei Patienten mit systemischem Lupus erythematodes und chronischer Polyarthritis

Horn, A.; Avenarius, H J; Deicher, H.

doi:10.1007/bf01648899

Cited by 1 publication

(1 citation statement)

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“…Mild thrombocytopenia is frequently observed in patients with SLE (13, 14). Several clinical studies of patients with SLE have suggested a significant role of platelets in the development of lupus nephritis (15–17). A previous study of SLE patients with biopsy‐proven nephritis demonstrated that the onset of thrombocytopenia was significantly correlated with nonhematologic disease episodes in clinical SLE (18).…”

Section: Discussionmentioning

confidence: 99%

Cappuccino mutation in an autoimmune‐prone strain of mice suggests a role of platelet function in the progression of immune complex crescentic glomerulonephritis

Yoshida¹,

Saiga²,

Hato³

et al. 2006

Arthritis & Rheumatism

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Objective. Crescent formation in the renal glomerulus is a typical manifestation of progressive glomerulopathy associated with fatal renal failure; therefore, its prevention is of clinical importance. Little is known about the pathogenic mechanism for crescent formation. This study was undertaken in an attempt to identify the events that are critical for crescent formation in immune complex crescentic glomerulonephritis (CGN) by analyzing a novel mutant strain of mice.Methods. A spontaneous mutant strain of mice was isolated from the autoimmune-prone strain EOD, which stably develops fatal CGN. The mutant phenotypes were assessed histopathologically, hematologically, and immunologically. The mutation was searched for with positional cloning using microsatellite markers.Results. Compared with wild-type EOD (WT-EOD) mice, mutant EOD (mut-EOD) mice showed marked improvement in CGN in conjunction with an improvement in spontaneous mortality. In WT-EOD mice, an inverse correlation between blood urea nitrogen concentration and blood platelet count and massive accumulation of platelets in the glomerulus were evident, suggesting that an accumulation of platelets in the glomerulus contributes to the progression of CGN. The mutant platelets showed an abnormal aggregation in response to collagen and thrombin, associated with a bleeding tendency in mut-EOD mice. Genetic analysis revealed a deleterious mutation in the cappuccino gene (cno), which encodes a protein that belongs to a complex called the biogenesis of lysosome-related organelle complex 1 and is profoundly involved in platelet function. Morphologic examination revealed a partial defect in dense body formation in the ␦-granule of platelets.Conclusion. The present findings suggest that platelet functions have a critical role in crescent formation in autoimmune GN.In systemic autoimmune disease, renal function is frequently impaired due to immune-mediated inflammation. An example is the occurrence of lupus nephritis in association with systemic lupus erythematosus (SLE). Immune complex (IC) deposition is detected in the affected glomeruli of patients with lupus nephritis, thus suggesting a pathogenic role of ICs in this manifestation. Animal models have further demonstrated the indispensable roles of some receptors such as the Fc receptor for IgG (Fc␥R) (1,2) and complement receptors (CRs) (3,4), proinflammatory factors such as cytokines and chemokines, and growth factors in the progression of glomerulonephritis (GN) following IC deposition. These findings readily confirm the existence of a longstanding pathogenic mechanism through which IC deposition initiates an inflammatory cascade by engaging Fc␥R and CRs and liberates a range of proinflammatory factors.

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Section: Discussionmentioning

confidence: 99%