Department of Nephrology and Kidney Transplantation, University Hospital of Patras, 26504 Patras, Greece.
Laboratory of Biology, Department of Biology, University of Patras, 26504 Patras, Greece.
Int J Mol Sci. 2024 Oct 10;25(20):10904. doi: 10.3390/ijms252010904.
Chronic antibody-mediated rejection in kidney transplantation is a common cause of graft loss in the late post-transplant period. In this process, the role of the classical complement activation pathway is crucial due to the formation of immune complexes between donor-specific antibodies (DSAs) and donor antigens and the attachment of the C1q complement fragment. This study aimed to determine the levels of circulating C1q immunocomplexes (CIC-C1q) and complement activation (CH50), in sensitized kidney transplant recipients (KTRs). In this cross-sectional study we used serum samples from KTRs with de novo or preformed DSAs ( = 14), KTRs without DSAs ( = 28), and 22 subjects with no history of chronic kidney disease (controls). C1q immunocomplexes and CH50 concentration in serum were measured with the enzyme immunoassay (EIA) kit MicroVue CIC-C1q (Quidel, Athens, OH, USA) and EIA kit MicroVue CH50 (Quidel, OH, USA), respectively. Higher concentrations of CIC-C1q was observed in KTRs with DSAs in comparison with controls and with KTRs with no DSAs (6.8 ± 2.7 and 4.8 ± 1.9 vs. 5.0 ± 1.2 μg Eq/mL, respectively, < 0.01). We found no difference in CIC-C1q between KTRs with no DSAs and controls. CIC-C1q levels were positively correlated with DSA titer. CH50 levels were decreased in KTRs with DSAs in comparison with controls and KTRs with no DSAs (39 ± 15 vs. 68 ± 40 and 71 ± 34 U Eq/mL, respectively, < 0.01). There was no difference in CH50 between DSA-negative KTRs and controls. Kidney transplant recipients with DSAs had increased serum levels of C1q immunocomplexes and increased classical pathway complement activation.
慢性抗体介导的排斥反应是移植后晚期移植物丢失的常见原因。在这个过程中，经典补体激活途径的作用至关重要，因为供体特异性抗体（DSA）与供体抗原之间形成免疫复合物，并且 C1q 补体片段附着。本研究旨在确定致敏肾移植受者（KTR）中循环 C1q 免疫复合物（CIC-C1q）和补体激活（CH50）的水平。在这项横断面研究中，我们使用了具有新出现或预先形成的 DSA 的 KTR（n = 14）、无 DSA 的 KTR（n = 28）和 22 名无慢性肾脏病史的受试者（对照组）的血清样本。用酶免疫测定（EIA）试剂盒 MicroVue CIC-C1q（Quidel，Athens，OH，USA）和 EIA 试剂盒 MicroVue CH50（Quidel，OH，USA）分别测量血清中的 C1q 免疫复合物和 CH50 浓度。与对照组和无 DSA 的 KTR 相比，具有 DSA 的 KTR 中 CIC-C1q 的浓度更高（分别为 6.8 ± 2.7 和 4.8 ± 1.9 与 5.0 ± 1.2 μg Eq/mL， < 0.01）。我们在无 DSA 的 KTR 和对照组之间未发现 CIC-C1q 差异。CIC-C1q 水平与 DSA 滴度呈正相关。与对照组和无 DSA 的 KTR 相比，具有 DSA 的 KTR 中的 CH50 水平降低（分别为 39 ± 15 与 68 ± 40 和 71 ± 34 U Eq/mL， < 0.01）。无 DSA 的 KTR 和对照组之间的 CH50 没有差异。具有 DSA 的 KTR 血清中 C1q 免疫复合物水平升高，经典途径补体激活增加。
