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Title: Application of complement component 4d immunohistochemistry to ABO-compatible and ABO-incompatible liver transplantation.
Authors: Salah, Adeeb
Fujimoto, Masakazu  kyouindb  KAKEN_id
Yoshizawa, Atsushi  kyouindb  KAKEN_id
Yurugi, Kimiko
Miyagawa-Hayashino, Aya
Sumiyoshi, Shinji
Minamiguchi, Sachiko  kyouindb  KAKEN_id
Uemoto, Shinji  kyouindb  KAKEN_id
Maekawa, Taira  kyouindb  KAKEN_id
Haga, Hironori  kyouindb  KAKEN_id
Author's alias: 羽賀, 博典
Issue Date: 27-Jan-2014
Publisher: Wiley
Journal title: Liver transplantation
Volume: 20
Issue: 2
Start page: 200
End page: 209
Abstract: Antibody-mediated rejection (AMR) is difficult to diagnose after ABO-compatible or ABO-identical (ABO-C) liver transplantation. To determine whether complement component 4d (C4d) immunostaining would be useful for diagnosing AMR, we compared the results of C4d immunohistochemistry for allograft biopsy samples with assays for anti-donor antibodies performed at the time of biopsy. One hundred fourteen patients with ABO-C grafts and 29 patients with ABO-incompatible (ABO-I) grafts were included. Linear C4d endothelial staining (identifiable with a 4× objective lens) or staining seen in 50% or more of the portal tracts was considered positive. Five of the 114 patients (4%) with ABO-C grafts and 15 of the 29 patients (52%) with ABO-I grafts showed C4d positivity. In the ABO-C cases, C4d positivity in late biopsy samples (≥30 days after transplantation) was associated with stage 2 or higher fibrosis (METAVIR score; P = 0.01) and with the presence of donor-specific anti-human leukocyte antigen DR antibodies (HLA-DR DSAs) with a mean fluorescence intensity > 5000 according to the Luminex single-antigen bead assay (P = 0.04). Conversely, the presence of HLA-DR DSAs was associated with the presence of stage 2 or higher fibrosis, acute cellular rejection, and C4d positivity. During the 2-year follow-up, neither C4d positivity nor HLA-DR DSAs were related to graft loss. Among ABO-I patients, C4d positivity was not associated with allograft dysfunction or fibrosis. Only 3 of the 15 C4d-positive patients (20%) showed periportal hemorrhagic edema, which could be a histological sign of AMR in ABO-I grafts, and they were the only cases associated with elevations in anti-donor A/B antibody titers. In conclusion, C4d endothelial positivity among ABO-C patients is an uncommon event that could be associated with chronic graft damage with or without clinical AMR. C4d positivity is common among ABO-I patients and may not be associated with allograft dysfunction if alloantibody titers are not elevated.
Rights: This is the accepted version of the following article: Salah, A., Fujimoto, M., Yoshizawa, A., Yurugi, K., Miyagawa-Hayashino, A., Sumiyoshi, S., Minamiguchi, S., Uemoto, S., Maekawa, T. and Haga, H. (2014), Application of complement component 4d immunohistochemistry to ABO-compatible and ABO-incompatible liver transplantation. Liver Transpl, 20: 200–209. doi: 10.1002/lt.23789, which has been published in final form at
This is not the published version. Please cite only the published version.
DOI(Published Version): 10.1002/lt.23789
PubMed ID: 24470446
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