Daniela Piancatelli1, Daniela Maccarone2, Alessia Colanardi3, Pierluigi Sebastiani3, Fabrizio D'Anselmi4, Samuele Iesari5, Barbara Binda4, Francesco Pisani6. 1. CNR-Institute of Translational Pharmacology (IFT), L'Aquila, Italy. Electronic address: daniela.piancatelli@cnr.it. 2. Regional Center for Organ Transplantation (CRT), S. Salvatore Hospital, L'Aquila, Italy. 3. CNR-Institute of Translational Pharmacology (IFT), L'Aquila, Italy. 4. General Surgery and Organ Transplantation, S. Salvatore Hospital, L'Aquila, Italy. 5. General Surgery and Organ Transplantation, S. Salvatore Hospital, L'Aquila, Italy; Pôle de Chirurgie Expérimentale et Transplantation, Institut de recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium. 6. General Surgery and Organ Transplantation, S. Salvatore Hospital, L'Aquila, Italy; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy.
Abstract
In the field of transplantation, expression of HLA-G, a nonclassical HLA molecule with immunosuppressive functions and limited gene polymorphism, is considered beneficial for graft acceptance; various studies have aimed to demonstrate this role in transplantation. Recently, in other clinical conditions, it has been observed that insulin resistance was associated with HLA-G14bpins/del polymorphism, the most studied regulatory polymorphism of this molecule. In the present study, plasma levels of the soluble form of HLA-G (sHLA-G) were analyzed in kidney transplant recipients (n = 103) with different HLA-G14bpins/del genotypes. In a group of 26 recipients, sHLA-G was detected before and after transplantation (1 year) to evaluate early variations. In 77 recipients, sHLA-G was detected after transplantation (3-24 years) and correlated with occurrence of long-term post-transplant morbidity (diabetes mellitus, hyperlipidemia, hypertension, obesity, etc.). METHODS: Levels of sHLA-G were measured in plasma with an enzyme-linked immunosorbent assay; HLA-G14bpins/del and HLA-G+3142C>G genotypes were assessed using direct polymerase chain reaction. RESULTS: Plasma levels of sHLA-G significantly decreased during the first year after transplantation (P = .019); no significant correlations were found with genotypes or early post-transplant events. Lower levels of sHLA-G were found in recipients with post-transplant diabetes mellitus or obesity carrying the HLA-G14bpins/ins (P = .006 and P = .003, respectively) or HLA-G+3142G/G genotypes. CONCLUSIONS: A complex modulation of HLA-G, which includes both immunologic and metabolic effects, could affect the risk for long-term post-transplant morbidity in kidney transplant recipients. Associations of HLA-G, diabetes, and obesity deserve to be investigated by deeply exploring HLA-G regulatory variants.
In the field of transplantation, expression of HLA-G, a nonclassical HLA molecule with immunosuppressive functions and limited gene polymorphism, is considered beneficial for graft acceptance; various studies have aimed to demonstrate this role in transplantation. Recently, in other clinical conditions, it has been observed that insulin resistance was associated with HLA-G14bpins/del polymorphism, the most studied regulatory polymorphism of this molecule. In the present study, plasma levels of the soluble form of HLA-G (sHLA-G) were analyzed in kidney transplant recipients (n = 103) with different HLA-G14bpins/del genotypes. In a group of 26 recipients, sHLA-G was detected before and after transplantation (1 year) to evaluate early variations. In 77 recipients, sHLA-G was detected after transplantation (3-24 years) and correlated with occurrence of long-term post-transplant morbidity (diabetes mellitus, hyperlipidemia, hypertension, obesity, etc.). METHODS: Levels of sHLA-G were measured in plasma with an enzyme-linked immunosorbent assay; HLA-G14bpins/del and HLA-G+3142C>G genotypes were assessed using direct polymerase chain reaction. RESULTS: Plasma levels of sHLA-G significantly decreased during the first year after transplantation (P = .019); no significant correlations were found with genotypes or early post-transplant events. Lower levels of sHLA-G were found in recipients with post-transplant diabetes mellitus or obesity carrying the HLA-G14bpins/ins (P = .006 and P = .003, respectively) or HLA-G+3142G/G genotypes. CONCLUSIONS: A complex modulation of HLA-G, which includes both immunologic and metabolic effects, could affect the risk for long-term post-transplant morbidity in kidney transplant recipients. Associations of HLA-G, diabetes, and obesity deserve to be investigated by deeply exploring HLA-G regulatory variants.
Authors: Siqi Liu; Nicolaas A Bos; Erik A M Verschuuren; Debbie van Baarle; Johanna Westra Journal: Front Immunol Date: 2022-06-13 Impact factor: 8.786