C4D staining of perioperative renal transplant biopsies
C4D staining of perioperative renal transplant biopsies
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DOI：
10.1097/00007890-200209150-00021
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发表时间：
2002-09-15
期刊：
影响因子：
6.2
通讯作者：
Montgomery, RA
中科院分区：
文献类型：
--
作者：
Haas, M;Ratner, LE;Montgomery, RA
背景。在肾移植活检中，小管周围毛细血管（ptc）中C4d的沉积已被证明是抗体介导（体液）排斥反应的敏感标志物。一些研究还表明，ptc中的C4d对体液排斥或至少对供体特异性抗体的存在具有特异性。然而，在其他研究中，超过40%因移植物功能障碍而进行的肾移植活检中发现PTC C4d沉积，心脏移植中毛细血管C4d沉积可能是由缺血性损伤引起的。为了测试C4d染色作为同种异体肾移植急性体液性排斥反应标志物的特异性，采用单克隆抗C4d抗体和荧光素异硫氰酸酯偶联二抗对90例肾移植活检的低温切片进行间接免疫荧光检测，其中包括35对移植前肾切片。同一移植物的1小时灌注后活检，另外12个移植物的灌注后活检和8个阳性对照（已知c4d阳性AHR的活检）。18个移植物为尸体，17个移植物为活体相关，12个移植物为活体无关（不包括对照组）。这些移植物中有13个移植物在移植后3 ~ 34天发生AHR。82例围手术期活检中仅有2例ptc呈C4d染色。两例围手术期活检分别为移植后5天和34天诊断为AHR的移植物的灌注后活检，并且，在每个病例中，由于交叉配型阳性（细胞毒性和流式细胞术），受体在移植前接受了血浆置换治疗，并且在移植时继续具有弱阳性的血流交叉配型。一次活检C4d染色为局灶性，另一次活检C4d染色为弥漫性；两次活检中，C4d染色相对较轻（0-4+评分为1+）。移植前活检未见C4d染色。所有含肾小球的活检均表现为线状毛细血管袢或系膜斑点染色，或两者兼有，灌注前和灌注后活检相似。阳性对照均显示ptcs弥漫性C4d染色。在一些抗供体抗体水平较低的受者中，ptc的C4d染色可早在移植后1小时出现。然而，在围手术期肾移植活检中，包括那些冷缺血时间长达41小时的尸体移植物，没有观察到这是缺血或缺血再灌注损伤的特征。
Background. Deposition of C4d in peritubular capillaries (PTCs) has been shown to be a sensitive marker for antibody-mediated (humoral) rejection in renal transplant biopsies. Some studies also suggest that C4d in PTCs is specific for humoral rejection or, at least, for the presence of donor-specific antibodies. However, in other studies, PTC C4d deposits were noted in more than 40% of renal transplant biopsies performed for graft dysfunction and capillary C4d deposition in heart transplants may result from ischemic injury.Methods. To test the specificity of C4d staining as a marker for acute humoral rejection ACR in renal allografts, indirect immunofluorescence using a monoclonal anti-C4d antibody and a fluorescein-isothiocyanate-conjugated secondary antibody was performed on cryostat sections of 90 renal transplant biopsies, including 35 pairs of preimplantation. and 1-hr postreperfusion biopsies of the same graft, postreperfusion biopsies of 12 additional grafts, and 8 positive controls (biopsies with known C4d-positive AHR). Eighteen grafts were cadaveric, 17 grafts were living-related, and 12 grafts were living-unrelated (excluding controls). Included in these grafts were 13 grafts that developed AHR 3 to 34 days posttransplantation.Results. Only 2 of 82 perioperative biopsies showed C4d staining in PTCs. Both perioperative biopsies were postreperfusion biopsies of grafts diagnosed with AHR 5 and 34 days posttransplantation, respectively, and, in each case, the recipient had been treated with plasmapheresis before transplantation because of a positive crossmatch (cytotoxic and flow cytometric) and continued to have a weakly positive flow crossmatch at the time of transplantation. In one biopsy, C4d staining was focal, and in the other biopsy, it was diffuse; in both biopsies, C4d staining was relatively mild (1+ on a 0-4+ scale). No C4d staining was noted on preimplantation biopsies of each graft. All biopsies that contained glomeruli showed linear capillary loop or blotchy mesangial staining, or both, which was similar in prereperfusion and postreperfusion biopsies. All positive controls showed diffuse C4d staining in PTCs.Conclusions. C4d staining in PTCs may be seen as early as 1 hr posttransplantation in some recipients with low levels of antidonor antibodies. However, this was not observed as a feature of ischemic or ischemia-reperfusion injury in perioperative renal transplant biopsies, including those of cadaveric grafts with cold ischemia times of as long as 41 hr.