Joosten Simone A, van Ham Vanessa, Borrias Maria C, van Kooten Cees, Paul Leendert C
Department of Nephrology, C3p, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Nephrol Dial Transplant. 2005 Apr;20(4):692-8. doi: 10.1093/ndt/gfh706. Epub 2005 Feb 8.
Chronic renal allograft rejection (CR) is the leading cause of late renal transplant failure. The histological lesions of CR may comprise glomerular basement membrane (GBM) duplications and mesangiolysis. Its pathogenesis is not yet completely understood, although lately humoral responses have been suggested to be important. Recently, we identified antibody responses directed against GBM antigens in the Fischer (F344) to Lewis (LEW) renal transplantation model. Immunofluorescent studies in this model also suggested deposition of antibodies on mesangial cells. Therefore, we hypothesized that antibodies were not only directed at GBM antigens but also to mesangial cell antigens.
F344 to LEW renal transplantations were performed and sera were collected. Pre- and post-transplantation sera were tested for antibody binding to donor rat mesangial cells (RMCs) cultured from F344 kidneys. Anti-mesangial cell antibodies were compared with anti-GBM antibodies measured in the same sera.
Post-transplant sera of F344 to LEW renal transplantations, but not LEW to F344, bound to F344 RMC in a dose-dependent manner. Whereas antibodies reactive with RMCs were not present before transplantation, all rats with CR developed antibodies. The antibodies were predominantly of the IgG1 isotype. Antibody binding to RMCs correlated with binding to F344 GBM. Pre-incubation with RMCs partially inhibited GBM binding, and RMC binding was inhibited by GBM. Antibody binding to RMCs did not result in complement activation or cell lysis.
LEW recipients of F344 grafts produce antibodies reactive with F344 RMCs. The antigens involved are similar to or at least share antigenic epitopes with antigens recognized in the GBM.
慢性肾移植排斥反应（CR）是肾移植后期失败的主要原因。CR的组织学病变可能包括肾小球基底膜（GBM）重复和系膜溶解。尽管最近有人提出体液反应很重要，但其发病机制尚未完全明确。最近，我们在Fischer（F344）到Lewis（LEW）肾移植模型中鉴定出针对GBM抗原的抗体反应。该模型中的免疫荧光研究还表明抗体沉积在系膜细胞上。因此，我们推测抗体不仅针对GBM抗原，还针对系膜细胞抗原。
进行F344到LEW的肾移植并收集血清。检测移植前和移植后的血清与从F344肾培养的供体大鼠系膜细胞（RMCs）的抗体结合情况。将抗系膜细胞抗体与同一血清中检测到的抗GBM抗体进行比较。
F344到LEW肾移植的移植后血清，但LEW到F344的移植后血清未出现，以剂量依赖方式与F344 RMC结合。移植前不存在与RMCs反应的抗体，而所有发生CR的大鼠均产生了抗体。这些抗体主要为IgG1同种型。抗体与RMCs的结合与与F344 GBM的结合相关。与RMCs预孵育可部分抑制GBM结合，而GBM可抑制RMC结合。抗体与RMCs的结合未导致补体激活或细胞裂解。
F344移植物的LEW受体产生与F344 RMCs反应的抗体。所涉及的抗原与GBM中识别的抗原相似或至少共享抗原表位。
