Soluble HLA-G molecules in Umbilical Cord Blood plasma as a marker of immunoregulatory ability

Human umbilical cord blood units (UCBs) are an alternative source to bone marrow (BM) and granulocyte colonystimulating factor (G-CSF) mobilized peripheral blood progenitor cells in allogeneic stem cell transplantation. The study of UCBs immunoregulatory systems is of interest to clarify the mechanisms involved in their ability to reduce incidence and severity of graft versus host disease (GvHD). HLA-G antigens are immunoregulatory molecules involved in the mesenchymal stromal cell (MSC) control of GvHD. Here we analyzed: i) the presence of soluble-HLA-G molecules in 85 UCB plasma; ii) the possible role of the HLA-G 14 bp polymorphism in regulating the quantitative production of sHLA-G molecules; iii) if CD34+ cells express HLA-G molecules during the early stages of differentiation and iv) if sHLA-G from UCB plasma sample is able to inhibit lymphoproliferation. The results showed elevated levels of sHLA-G in all the UCBs, with the predominance of the HLA-G5 isoform. HLA-G 14 bp polymorphism presented no implications in the regulation of HLA-G levels. HLA-G mRNA and protein were detected in in vitro CD34+ progeny (CFU-GEMM, CFU-GM and BFU-E) and interestingly we observed a significant correlation between sHLA-G levels and the number of CD34+ cell in UCB (p < 0.0001). UCB plasma samples suppressed lymphoproliferative response in a HLA-G dose-dependent manner and a negative correlation was observed between the sHLA-G concentrations and the residual lymphoproliferative response (p < 0.0001, rho = −0.851). Overall these data suggest a role for CD34+ derived haematopoietic progeny in producing sHLA-G in UCB and the possible functional effect of HLA-G molecules in the immunomodulatory functions of UCB. Our results propose the possible use of sHLA-G as a marker for the selection of the most suitable unit for allogeneic stem cell transplantation.