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

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.