Browne Gemma, Brown Paul A J, Tomson Charles R V, Fleming Stewart, Allen Andrew, Herriot Richard, Pusey Charles D, Rees Andrew J, Turner A Neil
Renal Medicine, Royal Infirmary of Edinburgh and University of Edinburgh, Scotland, United Kingdom.
Kidney Int. 2004 Feb;65(2):675-81. doi: 10.1111/j.1523-1755.2004.00428.x.
Post transplant anti-glomerular basement membrane (GBM) disease affects up to 5% of patients with Alport's syndrome. Defects in the COL4A5 gene are responsible for most cases, and alpha 5(IV)NC1 is the usual target for alloantibodies. Gene deletions are more commonly associated with this complication than are point mutations. The disease is severe in renal allografts and nearly always results in graft loss.
Three cases of retransplantation in Alport's syndrome are described here in detail. All cases were started on immunosuppressive therapy early in the course of their disease and one patient (case 2) received pre-emptive anti-T-cell therapy (Campath IH). Anti-GBM antibodies in these cases were investigated by standard anti-GBM enzyme-linked immunosorbent assay (ELISA), by indirect immunofluorescence, and by Western blotting using collagenase-digested human GBM and recombinant type IV collagen NC1 domains made in insect cells.
All cases showed early antibody and complement fixation to human GBM. Target alloantibodies were to alpha 5(IV)NC1 domain predominantly. Cases two and three gave negative results on standard ELISA for anti-GBM antibodies. Pathologic examination revealed crescentic glomerulonephritis, which was rapid in onset in case 1, blunted and less aggressive in case 3, and case 2 developed segmental necrosis without crescent formation. Neutrophilic infiltrates were an early feature in all 3 cases. All cases are compared with a review of all retransplanted cases in the literature.
Alport anti-GBM disease is a severe disease in retransplanted patients. Anti-T-cell therapy seemed to modify the pathologic findings but did not prevent graft loss. Longer term plasma exchange and mycophenolate mofetil may attenuate the illness, but in these cases did not prevent graft loss. Western blotting detected alloantibodies to alpha 5(IV) NC1 domain and is more sensitive and specific for this disease than standard ELISAs.
移植后抗肾小球基底膜（GBM）疾病影响多达5%的奥尔波特综合征患者。COL4A5基因缺陷是大多数病例的病因，α5（IV）NC1是同种抗体的常见靶点。与点突变相比，基因缺失更常与这种并发症相关。该疾病在肾移植中较为严重，几乎总会导致移植肾丧失。
本文详细描述了3例奥尔波特综合征再次移植的病例。所有病例在疾病早期均开始免疫抑制治疗，1例患者（病例2）接受了抢先抗T细胞治疗（Campath IH）。通过标准抗GBM酶联免疫吸附测定（ELISA）、间接免疫荧光以及使用胶原酶消化的人GBM和昆虫细胞中制备的重组IV型胶原NC1结构域进行的蛋白质印迹法，对这些病例中的抗GBM抗体进行了研究。
所有病例均显示早期抗体和补体与人GBM结合。靶向同种抗体主要针对α5（IV）NC1结构域。病例2和病例3的抗GBM抗体标准ELISA检测结果为阴性。病理检查显示为新月体性肾小球肾炎，病例1起病迅速，病例3较缓和且侵袭性较小，病例2出现节段性坏死但无新月体形成。中性粒细胞浸润是所有3例的早期特征。将所有病例与文献中所有再次移植病例的综述进行了比较。
奥尔波特抗GBM疾病在再次移植患者中是一种严重疾病。抗T细胞治疗似乎改变了病理表现，但未能防止移植肾丧失。长期血浆置换和霉酚酸酯可能减轻病情，但在这些病例中未能防止移植肾丧失。蛋白质印迹法检测到针对α5（IV）NC1结构域的同种抗体，对于该疾病比标准ELISA更敏感和特异。
