HLA-G 3′ untranslated region gene variants are promising prognostic factors for BK polyomavirus replication and acute rejection after living-donor kidney transplant

• Published in: Human immunology 2020-04, Vol.81 (4), p.141-146
• Main Authors: Rohn, Hana, Schwich, Esther, Tomoya Michita, Rafael, Schramm, Sabine, Dolff, Sebastian, Gäckler, Anja, Korth, Johannes, Heinemann, Falko M., Wilde, Benjamin, Trilling, Mirko, Horn, Peter A., Kribben, Andreas, Witzke, Oliver, Rebmann, Vera
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Adult; BK virus; BK Virus - physiology; Female; Genetic Association Studies; Genetic Predisposition to Disease - genetics; Genotype; Graft Rejection - genetics; Graft Rejection - immunology; HLA; HLA-G 3′UTR; HLA-G Antigens - genetics; Human leukocyte antigen-G; Humans; Kidney Diseases - genetics; Kidney Diseases - virology; Kidney transplantation; Kidney Transplantation - adverse effects; Living Donors; Male; Middle Aged; Polymorphism, Single Nucleotide; Polyomavirus nephropathy; Prognosis; Rejection; Virus Replication
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2019.09.011

The immunosuppressive non-classical human leukocyte antigen-G (HLA-G) promotes transplant tolerance as well as viral immune escape. HLA-G expression is associated with regulatory elements targeting certain single nucleotide polymorphisms (SNPs) in the HLA-G 3′ untranslated region (UTR). Thus, we evaluated the impact of HLA-G 3′UTR polymorphisms as surrogate markers for BK polyomavirus (BKPyV) replication or nephropathy (PyVAN) and acute cellular and antibody mediated rejection (ACR/AMR) in 251 living-donor kidney-transplant recipient pairs. After sequencing of the HLA-G 3′UTR, fourteen SNPs between +2960 and +3227 and the 14 bp insertion/deletion polymorphism, which arrange as UTR haplotypes, were identified. The UTR-4 haplotype in donors and recipients was associated with occurrence of BKPyV/PyVAN compared to the other UTR haplotypes. While the UTR-4 recipient haplotype provided protection against AMR, the UTR-2 donor haplotype was deleteriously associated with ACR/AMR. Deduction of the UTR-2/4 haplotypes to specific SNPs revealed that the +3003C variant (unique for UTR-4) in donors as well as in recipients is responsible for BKPyV/PyVAN and also provides protection against AMR; whereas the +3196G variant (unique for UTR-2) promotes allograft rejection. Thus, HLA-G 3′UTR variants are promising genetic predisposition markers both in donors and recipients that may help to predict susceptibility to either viral infectious complication of BKPyV or allograft rejection.