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首页> 外文期刊>Journal of the American Society of Nephrology: JASN >Complement activation in acute humoral renal allograft rejection: diagnostic significance of C4d deposits in peritubular capillaries.
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Complement activation in acute humoral renal allograft rejection: diagnostic significance of C4d deposits in peritubular capillaries.

机译:急性体液性肾移植排斥反应中的补体激活:肾小管周围毛细血管中C4d沉积物的诊断意义。

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摘要

The distinction between acute humoral rejection (AHR) and acute cellular rejection (ACR) in renal allografts is therapeutically important, but pathologically difficult. Since AHR is probably mediated by antibodies to the donor endothelium that activate the classical complement pathway, it was hypothesized that peritubular capillary C4d deposition might distinguish this group. Renal biopsies (n = 16) from 10 patients with AHR who had acute graft dysfunction, neutrophils in peritubular capillaries, and a concurrent positive cross-match were stained for C4d by immunofluorescence. Control biopsies for comparison showed ACR (n = 14), cyclosporin A toxicity (n = 6), or no abnormality (n = 4). Peribiopsy sera were tested for anti-donor HLA antibody. C4d deposited prominently and diffusely in the peritubular capillaries in all AHR biopsies (16 of 16). IgM and/or C3 were also present in 19 and 44%, respectively. With two-color immunofluorescence, C4d was localized in basement membranes (type IV collagen+) and in the endothelium (Ulex europaeus agglutinin-I+). In ACR, no more than trace C4d was found in peritubular capillaries (P < 0.0001 versus AHR), and no patient had anti-donor HLA antibodies (0 of 8); 27% had neutrophils in peritubular capillaries. One of six biopsies with cyclosporin A toxicity had similar C4d deposits, and circulating anti-donor class I antibody was detected. Grafts with AHR were lost (40%) more often than those with ACR (0%; P < 0.02). C4d in peritubular capillary walls distinguishes AHR from ACR, is more specific and sensitive than traditional criteria, and is a potentially valuable adjunct in the diagnosis of graft dysfunction.
机译:肾同种异体移植中急性体液排斥(AHR)和急性细胞排斥(ACR)之间的区别在治疗上很重要,但在病理上却很困难。由于AHR可能是由激活经典补体途径的供体内皮抗体介导的,因此假设肾小管周围毛细血管C4d沉积可区分这一组。通过免疫荧光法对来自10例急性移植物功能障碍,肾小管周围毛细血管中性粒细胞以及同时发生的阳性交叉匹配的AHR患者的肾活检(n = 16)进行了染色。用于比较的对照活检显示ACR(n = 14),环孢菌素A毒性(n = 6)或无异常(n = 4)。对周活检血清进行抗供体HLA抗体测试。在所有AHR活检中,C4d在肾小管周围毛细血管中明显且弥漫性沉积(16个中的16个)。 IgM和/或C3也分别以19%和44%存在。通过双色免疫荧光,C4d定位在基底膜(IV型胶原蛋白+)和内皮细胞(欧洲杯凝集素-I +)中。在ACR中,在肾小管周围毛细血管中发现的痕量C4d不多(相对于AHR,P <0.0001),并且没有患者具有抗供体HLA抗体(0/8);肾小管周围毛细血管中性粒细胞占27%。具有环孢菌素A毒性的六个活检样本之一具有相似的C4d沉积物,并且检测到循环的I类抗供体抗体。与ACR相比(A0%; P <0.02),与AHR相比损失更多(40%)。肾小管周围毛细血管壁中的C4d将AHR与ACR区别开来,比传统标准更具特异性和敏感性,并且在移植物功能障碍的诊断中可能具有潜在的价值。

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