PMID- 34671352 OWN - NLM STAT- MEDLINE DCOM- 20211223 LR - 20211223 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - The Association Between Single-Nucleotide Polymorphisms of Co-Stimulatory Genes Within Non-HLA Region and the Prognosis of Leukemia Patients With Hematopoietic Stem Cell Transplantation. PG - 730507 LID - 10.3389/fimmu.2021.730507 [doi] LID - 730507 AB - To avoid graft rejection, the hematopoietic stem cells with matched classical human leukocyte antigen (HLA) alleles are the primary choice for clinical allogeneic transplantation. However, even if the fully HLA-matched hematopoietic stem cells are used for transplantation, some patients still have poor prognosis after hematopoietic stem cell transplantation (HSCT), suggesting that the HLA system was not the only determinant of the outcomes of HSCT. In this study, we investigated whether the single-nucleotide polymorphisms (SNPs) of the co-stimulatory genes within non-HLA regions were related to the outcomes of HSCT. The genomic DNAs of 163 patients who had acute leukemia and received HSCT and their respective donors were collected for analysis. Thirty-four SNPs located in the four co-stimulatory genes including cytotoxic T-lymphocyte associated protein 4 (CTLA4), CD28, tumor necrosis factor ligand superfamily 4 (TNFSF4), and programmed cell death protein 1 (PDCD1) were selected to explore their relationship with the adverse outcomes after transplantation, including mortality, cytomegalovirus infection, graft-versus-host disease, and relapse. Our results revealed that nine SNPs in the CTLA4 gene, five SNPs in the PDCD1 gene, two SNPs in the TNFSF4 gene, and four SNPs in the CD28 gene were significantly associated with the occurrence of adverse outcomes post-HSCT. These SNPs may play important roles in immune response to allografts post-HSCT and can be the targets for developing strategy to identify appropriate donors. CI - Copyright (c) 2021 Chen, Chang, Wang, Lin, Hsu, Wang and Tseng. FAU - Chen, Ding-Ping AU - Chen DP AD - Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. AD - Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Chang, Su-Wei AU - Chang SW AD - Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. AD - Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan, Taiwan. FAU - Wang, Po-Nan AU - Wang PN AD - Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. FAU - Lin, Wei-Tzu AU - Lin WT AD - Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. FAU - Hsu, Fang-Ping AU - Hsu FP AD - Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. FAU - Wang, Wei-Ting AU - Wang WT AD - Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. FAU - Tseng, Ching-Ping AU - Tseng CP AD - Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. AD - Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211004 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (CD28 Antigens) RN - 0 (CTLA-4 Antigen) RN - 0 (CTLA4 protein, human) RN - 0 (HLA Antigens) RN - 0 (OX40 Ligand) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - 0 (TNFSF4 protein, human) SB - IM MH - Adolescent MH - Adult MH - Aged MH - CD28 Antigens/*genetics/immunology MH - CTLA-4 Antigen/*genetics/immunology MH - Child MH - Child, Preschool MH - Cytomegalovirus Infections/genetics/immunology MH - Donor Selection MH - Female MH - Graft vs Host Disease/genetics/immunology MH - HLA Antigens/*immunology MH - *Hematopoietic Stem Cell Transplantation/adverse effects/mortality MH - Humans MH - Infant MH - Leukemia/genetics/immunology/mortality/*surgery MH - Male MH - Middle Aged MH - OX40 Ligand/*genetics/immunology MH - *Polymorphism, Single Nucleotide MH - Programmed Cell Death 1 Receptor/*genetics/immunology MH - Recurrence MH - Risk Assessment MH - Risk Factors MH - Time Factors MH - Treatment Outcome MH - Young Adult PMC - PMC8520956 OTO - NOTNLM OT - CD28 OT - CTLA4 OT - PDCD1 (PD-1) OT - TNFSF4 OT - hematopoietic stem cell transplantation OT - non-HLA OT - single-nucleotide polymorphism COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/10/22 06:00 MHDA- 2021/12/24 06:00 PMCR- 2021/01/01 CRDT- 2021/10/21 06:08 PHST- 2021/06/25 00:00 [received] PHST- 2021/09/09 00:00 [accepted] PHST- 2021/10/21 06:08 [entrez] PHST- 2021/10/22 06:00 [pubmed] PHST- 2021/12/24 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.730507 [doi] PST - epublish SO - Front Immunol. 2021 Oct 4;12:730507. doi: 10.3389/fimmu.2021.730507. eCollection 2021.