title: Circulating and renal expression of HLA-G prevented chronic renal allograft dysfunction in Japanese recipients.
abstract: BACKGROUND
  Although the risk of acute rejection has been studied in renal transplanted patients, there is little data about the long-term renal survival effects of non-classical human leukocyte antigen class I (HLA-G) in Japanese patients.
  
  
  METHODS
  We investigated the changes in the estimated glomerular filtration rate (eGFR) for Japanese, and factors affecting the eGFR in 141 adult Japanese subjects whose allografts had survived for at least 1 year. Clinical background data, gender, HLA matching status, the total ischemic time, ABO incompatibility, immunosuppressive therapy, and the serum soluble(s) HLA-G5 level were examined. In addition, renal biopsy specimens from 32 cases, which were obtained before, or 2-4 weeks or one year after the transplant were also evaluated for HLA-G1/5 expression using monoclonal anti-HLA-G antibodies (clone 87G or 4H84).
  
  
  RESULTS
  The rates of change per year in the median eGFR (ΔeGFR) and sHLA-G5 were -1.5 ml/min/1.73 m2/year and 11.8 ng/ml, respectively. A positive correlation was detected between the ΔeGFR and sHLA-G5 (r = 0.188, p = 0.025). In multivariate regression analysis, sHLA-G5 and HLA-matching were significant predictors of an improvement in eGFR (beta for sHLA-G: 0.374, p = 0.009; beta for mismatching: -1.135, p = 0.045). The renal tubular epithelial cells (TEC) in 11 cases showed a perinuclear HLA-G1/5 expression after renal transplantation. The renal HLA-G1/5-positive patients displayed much better ΔeGFR (p < 0.05). In conclusion, the sHLA-G5 level and HLA matching status are independent predictors of renal allograft function, as determined by the ΔeGFR, in Japanese patients. HLA-G1/5 was also detected on TEC in the patients with favorable renal function.
authors.affiliation: Department of Nephrology, Kanazawa Medical University School of Medicine, Daigaku, Uchinada, Ishikawa, 920-0293, Japan. okushi@kanazawa-med.ac.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Okushi
authors.affiliation: Department of Nephrology, Kanazawa Medical University School of Medicine, Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Okino
authors.affiliation: Department of Nephrology, Kanazawa Medical University School of Medicine, Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Mukai
authors.affiliation: Department of Nephrology, Kanazawa Medical University School of Medicine, Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsui
authors.affiliation: Department of Nephrology, Kanazawa Medical University School of Medicine, Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Department of Nephrology, Kanazawa Medical University School of Medicine, Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Department of Nephrology, Kanazawa Medical University School of Medicine, Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Adachi
authors.affiliation: Department of Nephrology, Kanazawa Medical University School of Medicine, Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yamaya
authors.affiliation: Department of Nephrology, Kanazawa Medical University School of Medicine, Daigaku, Uchinada, Ishikawa, 920-0293, Japan. h-yoko@kanazawa-med.ac.jp.
authors.forename: Hitoshi
authors.identifier: http://orcid.org/0000-0002-7753-1366
authors.initials: H
authors.lastname: Yokoyama
mesh_terms: D000328:Adult; D064591:Allografts; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002908:Chronic Disease; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D006085:Graft Survival; D059951:HLA-G Antigens / Q000097:blood*; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007564:Japan; D007668:Kidney / Q000276:immunology* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D059951:HLA-G Antigens; D007166:Immunosuppressive Agents
keywords: Estimated glomerular filtration rate (eGFR); Non-classical human leukocyte antigen class I (HLA-G); Renal transplantation; Renal tubular epithelial cells