移植物抗宿主反应与造血干细胞移植术后膜性肾病

Graft-versus-host disease and membranous nephropathy in post-allogeneic haematopoietic stem cell transplantation

目的:分析异基因造血干细胞移植术后膜性肾病(MN)的临床病理特征,并探讨其与慢性移植物抗宿主反应(GVHD)之间的关系。方法:选取在我科经活检证实的5例异基因造血干细胞移植(Allo-HSCT)术后MN为研究对象,分析5例患者的临床表现,实验室结果以及肾脏病理形态学、免疫荧光及电镜的病理特点,并行IgG亚型免疫荧光染色,观察不同IgG亚型在肾小球分布的特点及与nephrin分布的关系。此外,利用Western印迹的方法,我们检测了患者血清中是否存在抗M型磷脂酶A2受体(PLA2R)自身抗体。结果:5例患者的临床病理特征如下:(1)移植前无肾脏病史及肾脏病家族史;(2)所有患者在出现蛋白尿的时候均合并存在慢性GVHD(cGVHD)的表现,且4例患者既往有急性GVHD(aGVHD)的病史,经过有效的抗GVHD治疗后,患者的蛋白尿也随之好转;(3)部分患者自身抗体检测阳性,肾组织伴有C4及C1q的沉积,提示体内存在自身免疫现象;(4)肾组织沉积的IgG以IgG4为主,其分布与nephrin一致;(5)抗PLA2R自身抗体的检测结果显示5例患者中仅有1例阳性,阳性率远低于特发性膜性肾病(IMN)的检测结果。结论:我们认为Allo-HSCT术后的MN也是cGVHD的一种表现形式,其发病机制可能与移植入的免疫细胞产生了抗宿主足细胞的抗体有关,且抗体的类型不同于IMN的抗PLA2R自身抗体。

Objective： To study the clinical and pathological features and pathogenesis of the patients with post-allogeneic haematopoietic stem cell transplantation （HSCT） membranous nephropathy （MN） and investigate the relationship between the post-allogeneic HSCT MN and graft-versus-host disease （GVHD）. Methodology：Five patients with post-allogeneic HSCT MN which proved by renal biopsy was involved in this study. The clinical manifestations, laboratory data, and morphology, immunefluorescence and electron microscopy of the renal pathology of those patients were analyzed. Moreover, the IgG subclasses in glomerular deposits and the co-deposition of nephrin and IgG4 were studied. Finally, We detected the Anti-PLA2R（M-type phospholipase A2 receptor） autoantibodies in serum samples from patients with post-allogeneic HSCT MN. Results：The following items are the clinical and pathological features of the 5 patients： （ 1 ） All of the 5 patients have no history and family history of kidney disease. （ 2 ） All patients were combined with the syndrome of chronic GVHD at the time of proteinuria presence, and 4 patients had a history of acute GVHD, after an effective anti-GVHD treatment, the patients＇ proteinuria also remissioned. （3） The autoantibodies for some of the patients were positive and accompanied by the deposition of C4 and Clq in kidney, suggesting the existence of autoimmune phenomenon. （4） The dominant subclass of IgG deposition was IgG4, the distribution of IgG4 was as same as nephrin. （5） One of the five patients have detected the M-type phospholipase A2 receptor in the serum, the positive rate is far lower than in idiopathic membranous nephropathy （IMN） patients. Conclusion： Our data suggested that the membranous nephropathy of Allo-HSCT patients is a form of cGVHD, the pathogenesis may be related to the anti podocyte antibody which produced by the transplanted immune cells, and the type of antibody is different from the anti-PLA2 R antibody of the IMN patients.