Endothelial lesion and complement activation in patients with Scleroderma Renal Crisis

Abstract In kidney biopsies reviews, scleroderma renal crisis (SRC) is characterized by vascular endothelial injuries, C4d deposits on peritubular vessels, and acute and chronic injuries coexisting on the same biopsy. The clinical signs of thrombotic microangiopathy (TMA) are described in systemic sclerosis (SSc), nevertheless, it has not been related to acute injuries described on kidney biopsies. We report a case of SRC in a patient with scleroderma-dermatomyositis overlap syndrome, which also showed clinical and histopathological data of TMA. On fundus examination, a severe acute hypertensive retinopathy was found. The kidney biopsy showed severe endothelial damage with widening of mucoid cells at the level of the intima, focal concentric proliferation on most small arterioles, and C3, C4d, and IgM deposits along the capillary walls. The genetic study of complement only showed the presence of membrane cofactor protein (MCP) risk haplotypes, without other genetic complement disorders. We understand that in a patient with TMA and SSc, the kidney damage would be fundamentally endothelial and of an acute type; moreover, we would observe clear evidence of complement activation. Once further studies correlate clinical-analytical data with anatomopathological studies, it is likely that we will be forced to redefine the SRC concept, focusing on the relationship between acute endothelial damage and complement activation.

摘要 在肾活检病理评阅中，硬皮病肾危象（scleroderma renal crisis, SRC）的特征为血管内皮损伤、肾小管周血管C4d沉积，且同一活检标本中同时存在急性与慢性损伤。尽管已有文献报道系统性硬化症（systemic sclerosis, SSc）患者可出现血栓性微血管病（thrombotic microangiopathy, TMA）的临床体征，但目前尚未将其与肾活检中观察到的急性损伤建立关联。本文报告1例合并硬皮病-皮肌炎重叠综合征（scleroderma-dermatomyositis overlap syndrome）的SRC患者，该患者同时具备TMA的临床与组织病理学特征。眼底检查可见严重急性高血压性视网膜病变。肾活检结果显示：重度内皮损伤，内膜层黏液样细胞增宽，多数小动脉可见局灶性同心性增生，毛细血管壁可见C3、C4d及IgM沉积。补体遗传学检测仅检出膜辅因子蛋白（membrane cofactor protein, MCP）风险单体型，未发现其他补体系统遗传性异常。我们认为，对于合并TMA与SSc的患者，其肾损伤本质上为内皮源性急性损伤；同时可观察到补体活化的明确证据。未来若有更多研究将临床-检验数据与病理解剖学研究结果相关联，我们或需重新定义SRC的概念，重点关注急性内皮损伤与补体活化之间的关联。