title: Association of anti-human leukocyte antigen and anti-angiotensin II type 1 receptor antibodies with liver allograft fibrosis after immunosuppression withdrawal.
abstract: BACKGROUND
  Many pediatric patients who receive a living-donor liver transplant undergo withdrawal of immunosuppression (IS). For them, the high incidence of long-term progressive graft fibrosis is of particular concern.
  
  
  METHODS
  We conducted a cross-sectional study including 81 pediatric patients who underwent IS withdrawal after living-donor liver transplant at Kyoto University Hospital and whose serum samples and pathological data could be obtained during the analysis period. We examined the association of donor-specific anti-human leukocyte antigen (HLA) antibody (DSA) and angiotensin II type 1 receptor antibody (anti-AT1R Ab) with posttransplant graft fibrosis. Normalized mean fluorescence intensity (MFI) 5,000 or higher and anti-AT1R Ab concentrations 17 U/mL or higher were both considered high level. The patients were classified into an advanced fibrosis group (AFG) (Ishak score ≥ 3) and a control group (CG) (Ishak score ≤ 2).
  
  
  RESULTS
  Only one patient demonstrated DSA class I. Among those who demonstrated DSA class II, more AFG patients than CG patients demonstrated high-level mean fluorescence intensity, although the difference was not significant (64% vs. 39%; P=0.053). The incidence of high-level DSA-DRB1, however, was significantly higher in the AFG than that in the CG (40% vs. 4%; P<0.001), but there was no significant difference in DSA-DQB1 or DSA-DRB345. High-level anti-AT1R Ab was significantly more frequent in the AFG than in the CG (65% vs. 36%; P=0.02). All patients with both high-level DSA-DRB1 and high-level anti-AT1R Ab were found to have advanced fibrosis (P<0.001).
  
  
  CONCLUSIONS
  Anti-AT1R Ab and DSA-DRB1 may be candidates as biomarkers of graft fibrosis; both HLA and non-HLA immunity may be involved in graft fibrosis after IS withdrawal.
authors.affiliation: 1 Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 2 Department of Gastroenterological Surgery, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan. 3 Terasaki Foundation Laboratory, Los Angeles, CA. 4 Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan. 5 Address correspondence to: Hidenori Ohe, M.D., Ph.D., Terasaki Foundation Laboratory, 11570 W. Olympic Blvd, Los Angeles, CA 90064.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohe
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Uchida
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshizawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hirao
authors.forename: Michiko
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Etsuko
authors.initials: E
authors.lastname: Maruya
authors.forename: Kimiko
authors.initials: K
authors.lastname: Yurugi
authors.forename: Rie
authors.initials: R
authors.lastname: Hishida
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
mesh_terms: D000328:Adult; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006680:HLA Antigens; D059811:HLA-DRB1 Chains; D006801:Humans; D007165:Immunosuppression Therapy; D007223:Infant; D007518:Isoantibodies / Q000097:blood*; D008103:Liver Cirrhosis / Q000209:etiology* / Q000276:immunology; D016031:Liver Transplantation / Q000009:adverse effects*; D019520:Living Donors; D008297:Male; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D023001:Transplantation Tolerance
chemical_list: D006680:HLA Antigens; D059811:HLA-DRB1 Chains; D007518:Isoantibodies; D044140:Receptor, Angiotensin, Type 1