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Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure
Journal of the American Society of Nephrology ( IF 10.3 ) Pub Date : 2018-09-01 , DOI: 10.1681/asn.2018020205
Elena G. Kamburova 1 , Bram W. Wisse 1 , Irma Joosten 2 , Wil A. Allebes 2 , Arnold van der Meer 2 , Luuk B. Hilbrands 3 , Marije C. Baas 3 , Eric Spierings 1 , Cornelis E. Hack 1 , Franka E. van Reekum 4 , Arjan D. van Zuilen 4 , Marianne C. Verhaar 4 , Michiel L. Bots 5 , Adriaan C.A.D. Drop 1 , Loes Plaisier 1 , Marc A.J. Seelen 6 , Jan Stephan Sanders 6 , Bouke G. Hepkema 7 , Annechien J.A. Lambeck 7 , Laura B. Bungener 7 , Caroline Roozendaal 7 , Marcel G.J. Tilanus 8 , Christina E. Voorter 8 , Lotte Wieten 8 , Elly M. van Duijnhoven 9 , Mariëlle A.C.J. Gelens 9 , Maarten H.L. Christiaans 9 , Frans J. van Ittersum 10 , Shaikh A. Nurmohamed 10 , Neubury M. Lardy 11 , Wendy Swelsen 11 , Karlijn A.M.I. van der Pant 12 , Neelke C. van der Weerd 12 , Ineke J.M. ten Berge 12 , Frederike J. Bemelman 12 , Andries J. Hoitsma 13 , Paul J.M. van der Boog 6 , Johan W. de Fijter 6 , Michiel G.H. Betjes 14, 15 , Sebastiaan Heidt 16 , Dave L. Roelen 16 , Frans H. Claas 16 , Henny G. Otten 1
Affiliation  

Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients.

Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay.

Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non–C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non–C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non–C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%.

Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.



中文翻译:

移植前C3d固定供体特异性抗HLA抗体与肾移植失败的风险增加无关

背景抗供体HLA的补体固定抗体被认为是肾移植的禁忌症。IgG单抗原珠(SAB)分析的一种改进方法可以检测结合C3d的抗HLA抗体。因为早期体液移植排斥被认为是补体介导的,所以这种基于SAB的技术可能为肾移植接受者的移植前风险分层提供有价值的工具。

方法以前,我们确定移植前供体特异性抗HLA抗体(DSA)与补体依赖性细胞毒性交叉匹配阴性移植物中长期移植失败的风险增加相关。在这项研究中,我们使用C3d SAB分析进一步表征了DSA阳性血清样品。

结果在567个移植前DSA阳性血清样本中,有97个(17%)包含至少一种C3d固定DSA,而470个(83%)具有非C3d固定DSA。移植后10年,具有C3d固定抗体的患者经死亡检查,经协变量调整的移植物存活率为60%,而具有非C3d固定DSA的患者的移植物存活率为64%(危险比,1.02; 95)。 %置信区间,与不固定C3d的DSA相比,固定C3d的DSA为0.70至1.48;P = 0.93)。没有DSA的患者10年移植存活率为78%。

结论移植前DSA的C3d固定能力与移植失败风险增加无关。

更新日期:2018-09-01
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