HLA-G in solid organ transplantation

This work focused on the role HLA-G on solid organ transplantation. A deletion/insertion polymorphism of 14-bp controls specific mRNA stability and protein levels of the HLAG. Different studies associate the HLA-G +14bp allele with lower mRNA levels and lower protein production. This polymorphism was analysed in 190 multiorgan cadaveric donors. Exon 8 ofHLA-Gwas amplified using specific primers and PCR products were sequenced with a 3100 Genetic Analyzer. Transplant outcome was analysed in 605 related recipients all transplanted at the Turin Transplant Centre. Transplants from donors with +14bp/+14bp genotype showed a better graft survival then those fromdonorswith otherHLA-Ggenotypes. It was highly significant in lung with 67% survival for +14bp/ +14bp genotype at five years after transplant vs 15% for other genotypes (Log-Rank Test P¼ 0.026). In kidney transplants, a slightly difference was noted (at 5 ys 91% vs 78; p: 0,09). Not significant differences in the heart and liver transplant were noted. This study evidenced that the influence of donor HLA-G genotype on survival diminish for transplant characterized by a worse prognosis such as HCV infections in liver or - in case of kidney recipients - PRA levels >50%, a second transplant and a higher number ofHLAMM.These results suggested that in the first post-transplant period the immunosuppressive treatments could be the main effectors against the acute rejection risk, independently by the HLA-G genotype. However, the +14bp/ +14bp donor genotypemay have a ‘‘protective’’ role against the chronic allograft damage which is mainly associated with endothelial cells injury. In fact, recent studies report that the immunosuppressive therapy is able alone to up-regulates soluble levels of HLA-G which induce apoptosis of endothelial cells binding to CD160 receptor.