Significance of Glomerular Capillary C4d Deposition in Kidney Allograft Biopsies with Microvascular Inflammation.

IF 1.8 4区医学 Q2 UROLOGY & NEPHROLOGY

Nephron Pub Date : 2025-08-01 DOI:10.1159/000547778

Shintaro Ochiai, Hideyo Oguchi, Masaki Muramatsu, Tetuo Mikami, Noriyuki Kounoue, Yoshihiro Itabashi, Takeshi Kawamura, Yujiro Aoki, Yuko Hamasaki, Ken Sakai

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Abstract

Aim: The aim of the study was to elucidate the clinical and histological significance of glomerular capillary C4d (GC-C4d) deposition in allograft biopsies with microvascular inflammation (MVI), indicating antibody-mediated rejection (AMR).

Methods: The study included MVI biopsies defined as Banff g score ≥1 and/or peritubular capillary (ptc) score ≥1, with available HLA class I and/or class II single antigen test results. Biopsies with ABO-incompatible transplantation and diagnosis of T-cell-mediated rejection without AMR were excluded. We analyzed 84 allograft MVI biopsies obtained from January 2017 to May 2023. GC-C4d positivity was evaluated by immunofluorescence.

Results: GC-C4d positivity was determined in 46 of 84 (54.8%) MVI biopsies. Multivariate logistic analysis identified Banff g score and ptc-C4d score as factors significantly related to GC-C4d positivity in MVI biopsies with Banff cg score 0-3, and ptc score and ptc-C4d score as significantly related to GC-C4d positivity in MVI biopsies with cg0. Multivariate linear regression analysis identified Banff cg score and ptc-C4d score as factors significantly related to GC-C4d score in MVI biopsies with Banff cg0-3, and cadaver and Banff ptc-C4d score were significantly related to GC-C4d score in MVI biopsies with cg0. In MVI biopsies with cg0-3, evaluation of GC-C4d and/or ptc-C4d positivity decreased the specificity from 100.0% to 76.9% but increased the sensitivity from 67.2% to 84.5%, compared with the evaluation of ptc-C4d positivity alone for the diagnosis of Banff 2022 AMR. Ten of 19 biopsies (52.6%) with ptc-C4d-negative AMR showed ptc-C4d-negative but GC-C4d-positive AMR.

Conclusion: GC-C4d-positive findings in MVI biopsies may reflect active lesions as well as ptc-C4d scoring, while a high GC-C4d score may reflect advanced cg lesions in MVI biopsies with cg0-3. The combined evaluation of GC-C4d and ptc-C4d in MVI biopsies may increase the diagnostic sensitivity for Banff 2022 AMR by reducing the diagnosis of "C4d-negative AMR."

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肾小球毛细血管C4d沉积在微血管炎症的同种异体肾移植活检中的意义。

目的：探讨肾小球毛细血管C4d （GC-C4d）沉积在伴有微血管炎症（MVI）的同种异体移植活检中提示抗体介导的排斥反应（AMR）的临床和组织学意义。方法：研究包括MVI活检定义为Banff g评分≥1和/或管周毛细血管（ptc）评分≥1，可用HLAⅠ和/或Ⅱ类单抗原检测结果。排除abo血型不相容的移植活检和诊断为T细胞介导的无AMR的排斥反应。我们分析了2017年1月至2023年5月获得的84例同种异体移植MVI活检。免疫荧光法检测GC-C4d阳性。结果：84例MVI活检中46例（54.8%）GC-C4d阳性。多因素logistic分析发现Banff g评分和ptc- c4d评分是Banff cg评分0-3分的MVI活检中GC-C4d阳性显著相关的因素，ptc评分和ptc- c4d评分与c0分的MVI活检中GC-C4d阳性显著相关。多元线性回归分析发现，Banff cg评分和ptc-C4d评分是与Banff c0 -3型MVI活检GC-C4d评分显著相关的因素，尸体评分和Banff ptc-C4d评分与c0型MVI活检GC-C4d评分显著相关。在c0 -3的MVI活检中，与单独评估ptc-C4d阳性相比，评估GC-C4d和/或ptc-C4d阳性将Banff 2022 AMR的特异性从100.0%降低到76.9%，但将敏感性从67.2%提高到84.5%。ptc- c4d阴性AMR的19例活检中有10例（52.6%）显示ptc- c4d阴性但gc - c4d阳性AMR。结论：MVI活检中GC-C4d阳性可能反映病变活动性和ptc-C4d评分，而GC-C4d评分高可能反映c0 -3 MVI活检中cg病变进展。在MVI活检中联合评估GC-C4d和ptc-C4d可能通过减少“c4d阴性AMR”的诊断来提高Banff 2022 AMR的诊断敏感性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nephron UROLOGY & NEPHROLOGY-

CiteScore

5.00

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0.00%

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期刊介绍： ''Nephron'' comprises three sections, which are each under the editorship of internationally recognized leaders and served by specialized Associate Editors. Apart from high-quality original research, ''Nephron'' publishes invited reviews/minireviews on up-to-date topics. Papers undergo an innovative and transparent peer review process encompassing a Presentation Report which assesses and summarizes the presentation of the paper in an unbiased and standardized way.