ASSOCIATION BETWEEN DE NOVO DONOR SPECIFIC HLA ANTIBODY, C4D STAINING IN RENAL GRAFT BIOPSY AND GRAFT OUTCOME: A SINGLE CENTER EXPERIENCE.

James Cicciarelli, Yong W Cho, Michael Koss, Kathryn Helstab-Houston, Robert Mendez, Noriyuki Kasahara, Ian V Hutchinson, Tariq Shah
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Abstract

In 69 renal transplant recipients (RTR), all had a functioning graft (SCr < 2.0) at one year. After one year, transplant dysfunction was observed and these 69 RTR were biopsied, tested for C4d deposition and donor specific antibodies (DSA). Of these 69 RTR, 29 (42%) showed C4d negativity, 27 (39%) were C4d positive and 13 (19%) were not diagnostic. Forty-nine (71%) recipients had HLA antibodies and 41 (59%) had DSA. The proportion of C4d positivity was significantly higher in patients with DSA (HLA Class I only, II only, and I & II) in comparison to patients without post-transplant HLA antibodies. The incidence of graft failure (including current SCr > 4.0) in RTR with HLA Class II antibodies (Class II only or I & II) was significantly higher than in RTR without post-transplant HLA antibodies (P=0.03).Even after amelioration of rejection, the RTR with Class II DSA group continued to fail beyond 2 years after transplantation when compared with the other 2 groups (None/NDSA or HLA Class I only), however, the difference in graft survival between HLA Class II and None/NDSA groups did not reach statistical significance (log-rank P=0.32). Significant association between C4d staining, post-transplant HLA Class II antibodies and graft failure strongly suggests the importance of post-transplant HLA antibodies. HLA Class II DSAs may be an indicator of chronic allograft nephropathy (CAN) proceeding to graft loss. We propose that amelioration of CAN graft loss may be affected by monitoring and identification of DSA with appropriate immunosuppression of these antibodies.

移植肾活检中新生供者特异性hla抗体、c4d染色与移植预后的关系:单中心经验
在69例肾移植受者(RTR)中,一年时所有移植肾功能正常(SCr < 2.0)。一年后,观察移植功能障碍,并对69例RTR进行活检,检测C4d沉积和供体特异性抗体(DSA)。69例RTR中,C4d阴性29例(42%),C4d阳性27例(39%),无诊断性13例(19%)。49例(71%)患者有HLA抗体,41例(59%)患者有DSA。与移植后无HLA抗体的患者相比,DSA患者(HLA仅为I类、仅为II类和I & II类)C4d阳性比例明显更高。HLA II类抗体(仅II类或I和II类)的RTR移植失败发生率(包括当前SCr > 4.0)显著高于未移植后HLA抗体的RTR (P=0.03)。即使在排异反应得到改善后,与其他2组(无/NDSA组或仅HLAⅰ类组)相比,ⅱ类DSA组的RTR在移植后2年仍持续失败,但HLAⅱ类组与无/NDSA组的移植物存活差异无统计学意义(log-rank P=0.32)。C4d染色、移植后HLA II类抗体与移植失败之间的显著相关性强烈提示移植后HLA抗体的重要性。HLA II类dsa可能是慢性同种异体移植肾病(CAN)进展到移植物丧失的一个指标。我们建议,通过监测和识别DSA并适当抑制这些抗体,可以改善CAN移植物损失。
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