Roccatello D, Morsica G, Picciotto G, Cesano G, Ropolo R, Bernardi M T, Cacace G, Cavalli G, Sena L M, Lazzarin A, Piccoli G, Rifai A
Immunopathology Centre (CMID) and Division of Nephrology and Dialysis USL 4 Institute of Nephrology, University of Turin, Italy.
Clin Exp Immunol. 1997 Oct;110(1):9-14. doi: 10.1046/j.1365-2249.1997.4751383.x.
The pathogenic mechanisms that lead to renal deposition of the cryoprecipitable IgM rheumatoid factor-IgG complexes in essential mixed cryoglobulinaemia (EMC) are unknown. Defective removal of cryoprecipitable complexes from the circulation has been postulated in EMC-associated nephritis. To test this hypothesis, the kinetics and fate of a trace dose of 123I-radiolabelled autologous cryoglobulins were analysed in 13 patients with EMC grouped according to renal involvement. The time course of radioactivity distribution in the blood and organ uptake were measured by gamma camera scintigraphy. In blood sampled 30-300 s after injection, only a minor fraction (< 15%) of the circulating cryoglobulins bound to the erythrocytes, suggesting the elimination mechanisms are independent of binding to CR1 on erythrocytes. The overall blood disappearance curve showed a fast (< or = 1 min) and slow (> 4 h) biphasic pattern. In patients with quiescent or mild nepthritis, the liver and to a lesser extent the spleen were the major organs that mediated the rapid uptake and processing of the cryoglobulins from the circulation. In contrast, patients with active mesangiocapillary glomerulonephritis showed significantly (P < 0.001) less hepatic uptake, low liver-to-precordium ratio, and slower processing of cryoglobulins, prolonged liver mean transit time, than quiescent patients or mild nephritis patients. To elucidate the role and influence of HCV infection in the pathogenesis of EMC-nephritis, sera and cryoglobulins from all patients were assayed for HCV. None of the control group cases without nephritis showed any evidence of HCV-RNA in serum or cryoglobulin pellet. In contrast, all 10 EMC-nephritis patients' sera, and eight corresponding cryoglobulin pellets contained HCV-RNA. Collectively, these findings suggest an impaired reticuloendothelial system removal of IgM-IgG-HCV complexes may underlie their renal deposition.
导致原发性混合性冷球蛋白血症（EMC）中可冷沉淀的IgM类风湿因子-IgG复合物在肾脏沉积的致病机制尚不清楚。在EMC相关性肾炎中，曾推测循环中可冷沉淀复合物的清除存在缺陷。为验证这一假说，对13例根据肾脏受累情况分组的EMC患者，分析了微量123I放射性标记的自体冷球蛋白的动力学和转归。通过γ相机闪烁显像测量血液中放射性分布的时间进程和器官摄取情况。注射后30 - 300秒采集的血液样本中，只有一小部分（<15%）循环冷球蛋白与红细胞结合，提示清除机制独立于与红细胞上CR1的结合。整体血液消失曲线呈现快速（≤1分钟）和缓慢（>4小时）的双相模式。在静止或轻度肾炎患者中，肝脏以及程度较轻的脾脏是介导从循环中快速摄取和处理冷球蛋白的主要器官。相比之下，与静止患者或轻度肾炎患者相比，活动性系膜毛细血管性肾小球肾炎患者的肝脏摄取显著减少（P<0.001），肝/心前区比值低，冷球蛋白处理较慢，肝脏平均通过时间延长。为阐明丙型肝炎病毒（HCV）感染在EMC肾炎发病机制中的作用和影响，对所有患者的血清和冷球蛋白进行了HCV检测。无肾炎的对照组病例血清或冷球蛋白沉淀中均未显示HCV - RNA的任何证据。相比之下，所有10例EMC肾炎患者的血清以及8份相应的冷球蛋白沉淀均含有HCV - RNA。总体而言，这些发现提示网状内皮系统对IgM - IgG - HCV复合物清除受损可能是其在肾脏沉积的基础。
