Role of HLA‐G as a Predictive Marker of Low Risk of Chronic Rejection in Lung Transplant Recipients: A Clinical Prospective Study

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.

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