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Significance of Glomerular Capillary C4d Deposition in Kidney Allograft Biopsies with Microvascular Inflammation
Shintaro Ochiai1, Hideyo Oguchi2, Masaki Muramatsu1
1Department of Nephrology, Toho University Faculty of Medicine, Tokyo, Japan.
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."
