Acute humoral rejection and C4d immunostaining in ABO blood type-incompatible liver transplantation.
Complement C4d deposition in graft capillaries has been reported to be associated with antibody-mediated rejection in kidney and other solid organ transplantation. The correlation of C4d deposits and humoral rejection in liver transplants, however, is not well understood. We investigated the C4d immunostaining pattern in 34 patients whose liver biopsy was taken within the first 3 postoperative weeks for suspected acute rejection after ABO blood type-incompatible liver transplantation. The staining pattern was classified as positive (portal stromal staining), indeterminate (endothelial staining only), and negative (no staining). Positive C4d immunostaining was seen in 17 (50%) patients and was significantly associated with high (x64 or more) postoperative antidonor A/B antibody (immunoglobulin M (IgM)) titers (88 vs. 35%, P = 0.002) and poorer overall survival rate (41 vs. 88%, P = 0.007). Ten of 11 (91%) cases with histological acute humoral rejection (periportal edema and necrosis (PEN) or portal hemorrhagic edema) were positive for C4d, all of which showed high postoperative antibody titers. The other histologies associated with C4d positivity was purulent cholangitis (n = 4), coagulative hepatocyte necrosis (n = 1), acute cellular rejection (n = 1), and hepatocanalicular cholestasis (n = 1). Full clinical recovery was observed in only 6 of 17 (35%) C4d-positive patients, and tended to be associated with a lower rejection activity index (RAI). In conclusion, our study indicates that C4d deposits in the portal stroma can be a hallmark of acute humoral rejection in ABO-incompatible liver transplantation, and allograft damage can be reversible in a minority of cases.
Laboratory of Anatomic Pathology, Kyoto University, Kyoto, Japan. haga@kuhp.kyoto-u.ac.jp
Hironori
H
Haga
Hiroto
H
Egawa
Yasuhiro
Y
Fujimoto
Mikiko
M
Ueda
Aya
A
Miyagawa-Hayashino
Takaki
T
Sakurai
Tomoko
T
Okuno
Itsuko
I
Koyanagi
Yasutsugu
Y
Takada
Toshiaki
T
Manabe
D000017:ABO Blood-Group System; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001707:Biopsy, Needle; D001787:Blood Group Incompatibility / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015935:Complement C4b / Q000032:analysis / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016031:Liver Transplantation / Q000009:adverse effects* / Q000379:methods; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis / Q000276:immunology*; D011183:Postoperative Complications / Q000453:epidemiology / Q000276:immunology*; D011336:Probability; D012189:Retrospective Studies; D018570:Risk Assessment; D018709:Statistics, Nonparametric
D000017:ABO Blood-Group System; D015415:Biomarkers; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d