title: Significance of C4d staining in ABO-identical/compatible liver transplantation.
abstract: Complement degradation product C4d has become an important marker of humoral or antibody-mediated rejection in renal and heart allograft biopsies. Although there have been several reports on the detection of C4d in liver allografts, the significance of C4d in liver transplantation and its relationship with humoral rejection are still not clear. We investigated the frequency and pattern of C4d staining in liver allograft biopsies with reference to preoperative lymphocyte crossmatch tests, which detect donor-reactive lymphocyte antibody. Survival rates at 5 years were 77% for crossmatch-negative patients and 53% for crossmatch-positive patients (P=0.009). In crossmatch-negative patients, reproducible positive staining was obtained in 28 of 86 (33%) biopsies taken within 90 days after transplantation and 33 of 96 (34%) biopsies 90 days or after transplantation. Most C4d staining was observed in the portal areas, and no clear correlation was observed between C4d positivity and histological diagnosis. In crossmatch-positive patients, 9 of 11 (82%) biopsies showed positivity for C4d. C4d stained perivenular areas as well as portal areas. Histology of crossmatch-positive patients included acute rejection and cholangitis, but did not include periportal changes that were seen in humoral rejection in ABO-incompatible liver transplantation. In summary, focal C4d deposition was seen in various types of liver allograft injury and had little clinical impact on crossmatch-negative patients, but extensive C4d staining in crossmatch-positive patients may be associated with humoral rejection and poor graft survival.
authors: Laboratory of Diagnostic Pathology, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors: Hiromi
authors: H
authors: Sakashita
authors: Hironori
authors: H
authors: Haga
authors: Eishi
authors: E
authors: Ashihara
authors: Mei-Chin
authors: MC
authors: Wen
authors: Hiroaki
authors: H
authors: Tsuji
authors: Aya
authors: A
authors: Miyagawa-Hayashino
authors: Hiroto
authors: H
authors: Egawa
authors: Yasutsugu
authors: Y
authors: Takada
authors: Taira
authors: T
authors: Maekawa
authors: Shinji
authors: S
authors: Uemoto
authors: Toshiaki
authors: T
authors: Manabe
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003181:Complement C4 / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007518:Isoantibodies / Q000276:immunology; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D000017:ABO Blood-Group System; D015415:Biomarkers; D003181:Complement C4; D007518:Isoantibodies