Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
Pathol Int. 2011 Jan;61(1):34-41. doi: 10.1111/j.1440-1827.2010.02608.x. Epub 2010 Nov 5.
Thrombotic microangiopathy (TMA) is a known complication of hematopoietic stem cell transplantation (HSCT). The pathogenesis of TMA is controversial but considered to involve various factors such as total body irradiation, use of calcineurin inhibitors for prophylaxis against graft versus host disease (GVHD), viral infection, and GVHD. Herein we describe a case with renal TMA after HSCT, which was probably associated with antibody-mediated endothelial cell injury from chronic GVHD (termed here 'chronic humoral GVHD'). A 49-year-old man presented two years after HSCT with renal dysfunction and proteinuria but without the clinical features of TMA. Histopathological examination of renal biopsy showed chronic glomerular endothelial cell injury with double contour of the glomerular basement membrane, microthrombi and the deposition of complement split product C4d along the glomerular capillaries. Renal tubulitis and peritubular capillaritis were also noted with a multilayered basement membrane and patchy C4d deposition on peritubular capillaries. These findings resemble those of chronic antibody-mediated rejection after kidney transplantation. Furthermore, C4d deposition suggests complement activation. Although circulating anti-blood type and anti-human leukocyte antigen antibodies were not detected, the renal TMA in this case was probably associated with chronic humoral GVHD.
血栓性微血管病（TMA）是造血干细胞移植（HSCT）的已知并发症。TMA 的发病机制存在争议，但被认为涉及多种因素，如全身照射、使用钙调神经磷酸酶抑制剂预防移植物抗宿主病（GVHD）、病毒感染和 GVHD。本文描述了一例 HSCT 后发生肾 TMA 的病例，可能与慢性 GVHD 引起的抗体介导的内皮细胞损伤有关（此处称为“慢性体液性 GVHD”）。一名 49 岁男性在 HSCT 后两年出现肾功能障碍和蛋白尿，但无 TMA 的临床特征。肾活检的组织病理学检查显示慢性肾小球内皮细胞损伤，肾小球基底膜双层轮廓，微血栓形成，以及补体裂解产物 C4d 沿肾小球毛细血管沉积。肾小管炎和肾小管周围毛细血管炎也伴有多层基底膜和肾小管周围毛细血管 C4d 沉积斑。这些发现类似于肾移植后慢性抗体介导的排斥反应。此外，C4d 沉积提示补体激活。尽管未检测到循环血型抗体和抗人类白细胞抗原抗体，但本例肾 TMA 可能与慢性体液性 GVHD 有关。
