Role and expression of non-classical human leukocyte antigen-G in renal transplanted allografts.

ABSTRACT

BACKGROUND: The non-classical class I molecule human leukocyte antigen-G (HLA-G) has great potential to modulate the immune response. However, the mechanism underlying HLA-G induction remains unknown. Therefore, this study aimed to determine the factors that induce HLA-G expression on proximal tubular epithelial cells (pTECs) in renal transplanted allografts in vivo and in vitro. METHODS: This study included 40 adult Japanese patients with renal allografts (35 and five patients with kidneys from living and deceased donors, respectively) who survived for at least 1 year. We evaluated HLA-G1/5 expression using an immunofluorescence method and investigated the induction of HLA-G expression in primary cultured human pTECs by cytokines and immunosuppressants. RESULTS: The HLA-G expression was identified in the perinuclear region or on the basement membrane of pTECs of renal biopsy tissue in 12 (30%) of 40 patients at 2-4 weeks and at 1 year following transplantation. A reduction of 30% in the estimated glomerular filtration rate was lower in the HLA-G-positive group than that of the negative group (p = 0.016). Cox proportional hazard models also demonstrated that HLA-G1/5 expression on pTECs was an independent predictor of improved renal allograft function (hazard ratio, 0.189; 95% CI 0.041-0.850, p = 0.030). Interferon-beta was the most powerful inducer of HLA-G expression in vitro, whereas the immunosuppressants everolimus, tacrolimus, cyclosporin, and dexamethasone did not induce any expression. CONCLUSION: Unlike immunosuppressants, acquired HLA-G expression might confer long-term renal preservation effects in renal transplanted allografts.