Shintaro Ochiai, Hideyo Oguchi, Masaki Muramatsu, Tetuo Mikami, Noriyuki Kounoue, Yoshihiro Itabashi, Takeshi Kawamura, Yujiro Aoki, Yuko Hamasaki, Ken Sakai
{"title":"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。","authors":"Shintaro Ochiai, Hideyo Oguchi, Masaki Muramatsu, Tetuo Mikami, Noriyuki Kounoue, Yoshihiro Itabashi, Takeshi Kawamura, Yujiro Aoki, Yuko Hamasaki, Ken Sakai","doi":"10.1159/000547778","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.\"</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-9"},"PeriodicalIF":1.8000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Significance of Glomerular Capillary C4d Deposition in Kidney Allograft Biopsies with Microvascular Inflammation.\",\"authors\":\"Shintaro Ochiai, Hideyo Oguchi, Masaki Muramatsu, Tetuo Mikami, Noriyuki Kounoue, Yoshihiro Itabashi, Takeshi Kawamura, Yujiro Aoki, Yuko Hamasaki, Ken Sakai\",\"doi\":\"10.1159/000547778\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.\\\"</p>\",\"PeriodicalId\":18998,\"journal\":{\"name\":\"Nephron\",\"volume\":\" \",\"pages\":\"1-9\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2025-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nephron\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000547778\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nephron","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000547778","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
Significance of Glomerular Capillary C4d Deposition in Kidney Allograft Biopsies with Microvascular Inflammation.
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."
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.
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