title: Role of HLA-G as a predictive marker of low risk of chronic rejection in lung transplant recipients: a clinical prospective study.
abstract: Human leukocyte antigen G (HLA-G) expression is thought to be associated with a tolerance state following solid organ transplantation. In a lung transplant (LTx) recipient cohort, we assessed (1) the role of HLA-G expression as a predictor of graft acceptance, and (2) the relationship between (i) graft and peripheral HLA-G expression, (ii) HLA-G expression and humoral immunity and (iii) HLA-G expression and lung microenvironment. We prospectively enrolled 63 LTx recipients (median follow-up 3.26 years [min: 0.44-max: 5.03]). At 3 and 12 months post-LTx, we analyzed graft HLA-G expression by immunohistochemistry, plasma soluble HLA-G (sHLA-G) level by enzyme-linked immunosorbent assay, bronchoalveolar lavage fluid (BALF) levels of cytokines involved in chronic lung allograft dysfunction (CLAD) and anti-HLA antibodies (Abs) in serum. In a time-dependent Cox model, lung HLA-G expression had a protective effect on CLAD occurrence (hazard ratio: 0.13 [0.03-0.58]; p = 0.008). The same results were found when computing 3-month and 1-year conditional freedom from CLAD (p = 0.03 and 0.04, respectively [log-rank test]). Presence of anti-HLA Abs was inversely associated with graft HLA-G expression (p = 0.02). Increased BALF level of transforming growth factor-β was associated with high plasma sHLA-G level (p = 0.02). In conclusion, early graft HLA-G expression in LTx recipients with a stable condition was associated with graft acceptance in the long term.
authors.affiliation: Service de Pneumologie B et de Transplantation Pulmonaire, Centre Hospitalier Universitaire (CHU) Bichat-Claude Bernard, Paris, France; Faculté de Médecine Denis Diderot, Université Paris 7, Paris, France; Assistance Publique des Hôpitaux de Paris (AP-HP), Paris, France; DHU Fire, Paris, France; CEA, Institut des Maladies Emergentes et des Therapies Innovantes (IMETI), Service de Recherche en Hemato-Immunologie (SRHI), Hopital Saint-Louis, Paris, France; Sorbonne Paris Cité, University Paris Diderot, IUH, Hopital Saint-Louis, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Brugière
authors.forename: G
authors.initials: G
authors.lastname: Thabut
authors.forename: I
authors.initials: I
authors.lastname: Krawice-Radanne
authors.forename: R
authors.initials: R
authors.lastname: Rizzo
authors.forename: G
authors.initials: G
authors.lastname: Dauriat
authors.forename: C
authors.initials: C
authors.lastname: Danel
authors.forename: C
authors.initials: C
authors.lastname: Suberbielle
authors.forename: H
authors.initials: H
authors.lastname: Mal
authors.forename: M
authors.initials: M
authors.lastname: Stern
authors.forename: C
authors.initials: C
authors.lastname: Schilte
authors.forename: M
authors.initials: M
authors.lastname: Pretolani
authors.forename: E D
authors.initials: ED
authors.lastname: Carosella
authors.forename: N
authors.initials: N
authors.lastname: Rouas-Freiss
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000097:blood* / Q000453:epidemiology*; D059951:HLA-G Antigens / Q000097:blood*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000032:analysis; D066027:Transplant Recipients
chemical_list: D015415:Biomarkers; D059951:HLA-G Antigens; D016212:Transforming Growth Factor beta
keywords: Bronchiolitis obliterans (BOS); clinical research/practice; clinical trial; immune regulation; immunobiology; lung (allograft) function/dysfunction; lung transplantation/pulmonology; tolerance; translational research/science