LIMS1 risk genotype and T cell-mediated rejection in kidney transplant recipients. 2021

Yasar Caliskan, and Gonca Karahan, and Sebahat Usta Akgul, and Safak Mirioglu, and Yasemin Ozluk, and Halil Yazici, and Erol Demir, and Ahmet B Dirim, and Aydin Turkmen, and John Edwards, and Fatma Oguz Savran, and Mehmet S Sever, and Krzysztof Kiryluk, and Ali Gharavi, and Krista L Lentine
Division of Nephrology, Saint Louis University, St. Louis, MO, USA.

This study aims to examine the association of LIM zinc finger domain containing 1 (LIMS1) genotype with allograft rejection in an independent kidney transplant cohort. We genotyped 841 kidney transplant recipients for the LIMS1 rs893403 variant by Sanger sequencing followed by polymerase chain reaction confirmation of the deletion. Recipients who were homozygous for the LIMS1 rs893403 genotype GG were compared with the AA/AG genotypes. The primary outcome was T cell-mediated or antibody-mediated rejection (TCMR or ABMR, respectively) and secondary outcome was allograft loss. After a median follow-up of 11.4 years, the rate of TCMR was higher in recipients with the GG genotype (n = 200) compared with the AA/AG genotypes (n = 641) [25 (12.5%) versus 35 (5.5%); P = 0.001] while ABMR did not differ by genotype [18 (9.0%) versus 62 (9.7%)]. Recipients with the GG genotype had 2.4 times higher risk of TCMR than those who did not have this genotype [adjusted hazard ratio2.43 (95% confidence interval 1.44-4.12); P = 0.001]. A total of 189 (22.5%) recipients lost their allografts during follow-up. Kaplan-Meier estimates of 5-year (94.3% versus 94.4%; P = 0.99) and 10-year graft survival rates (86.9% versus 83.4%; P = 0.31) did not differ significantly in the GG versus AA/AG groups. Our study demonstrates that recipient LIMS1 risk genotype is associated with an increased risk of TCMR after kidney transplantation, confirming the role of the LIMS1 locus in allograft rejection. These findings may have clinical implications for the prediction and clinical management of kidney transplant rejection by pretransplant genetic testing of recipients and donors for LIMS1 risk genotype.

UI MeSH Term Description Entries
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006084 Graft Rejection An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. Transplant Rejection,Rejection, Transplant,Transplantation Rejection,Graft Rejections,Rejection, Graft,Rejection, Transplantation,Rejections, Graft,Rejections, Transplant,Rejections, Transplantation,Transplant Rejections,Transplantation Rejections
D006085 Graft Survival The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. Graft Survivals,Survival, Graft,Survivals, Graft
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D016030 Kidney Transplantation The transference of a kidney from one human or animal to another. Grafting, Kidney,Renal Transplantation,Transplantation, Kidney,Transplantation, Renal,Kidney Grafting,Kidney Transplantations,Renal Transplantations,Transplantations, Kidney,Transplantations, Renal
D048868 Adaptor Proteins, Signal Transducing A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes Signal Transducing Adaptor Proteins
D060588 LIM Domain Proteins A large class of structurally-related proteins that contain one or more LIM zinc finger domains. Many of the proteins in this class are involved in intracellular signaling processes and mediate their effects via LIM domain protein-protein interactions. The name LIM is derived from the first three proteins in which the motif was found: LIN-11, Isl1 and Mec-3.
D064591 Allografts Tissues, cells, or organs transplanted between genetically different individuals of the same species. Allogeneic Grafts,Allogeneic Transplants,Homografts,Homologous Transplants,Allogeneic Graft,Allogeneic Transplant,Allograft,Graft, Allogeneic,Grafts, Allogeneic,Homograft,Homologous Transplant,Transplant, Allogeneic,Transplant, Homologous,Transplants, Allogeneic,Transplants, Homologous

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