Dataset Information

Associations between HVEM/LIGHT/BTLA/CD160 polymorphisms and the occurrence of antibody-mediate rejection in renal transplant recipients.

ABSTRACT: Antibody-mediated rejection (ABMR) is a serious complications that can occur following renal transplantation. The production of donor-specific antibodies by the humoral immune response can trigger costimulatory signals, which are crucial in activating immune cells, and therefore, playing a potential role in ABMR. To investigate the role of HVEM/LIGHT/BTLA/CD160 polymorphisms in ABMR, we retrospectively analyzed 200 renal transplant recipients. We adopted next-generation sequencing (NGS) to identify HVEM/LIGHT/BTLA/CD160 single-nucleotide polymorphisms (SNPs) in the genotypes of these patients. We divided the patients into two groups: those with ABMR and those who were stable. We adopted multiple models and performed regression analysis after adjusting for multiple confounding variables, to determine the correlation between the SNPs and ABMR. We obtained 41 high-quality SNPs readouts. However, we did not observe any significant association between these polymorphisms and the pathogenesis of ABMR in any of the models.Nevertheless, since there is evidence suggesting the involvement of costimulatory signals in graft rejection, further research should be conducted to better understand how genetic polymorphisms may be involved in ABMR.

SUBMITTER: Wang Z

PROVIDER: S-EPMC5725004 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Associations between <i>HVEM/LIGHT/BTLA/CD160</i> polymorphisms and the occurrence of antibody-mediate rejection in renal transplant recipients.

Wang Zijie Z Wang Ke K Yang Haiwei H Han Zhijian Z Tao Jun J Chen Hao H Ge Yuqiu Y Guo Miao M Suo Chuanjian C Wei Ji-Fu JF Tan Ruoyun R Gu Min M

Oncotarget 20171019 59

Antibody-mediated rejection (ABMR) is a serious complications that can occur following renal transplantation. The production of donor-specific antibodies by the humoral immune response can trigger costimulatory signals, which are crucial in activating immune cells, and therefore, playing a potential role in ABMR. To investigate the role of <i>HVEM/LIGHT/BTLA/CD160</i> polymorphisms in ABMR, we retrospectively analyzed 200 renal transplant recipients. We adopted next-generation sequencing (NGS) t ...[more]

PMID: 29245962

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Project description:Background and objectivesThe current allocation algorithm for deceased donor kidney transplantation takes into consideration HLA mismatches at the ABDR loci but not HLA mismatches at other loci, including HLA-DQ. However, the independent effects of incompatibilities for the closely linked HLA-DQ antigens in the context of HLA-DR antigen matched and mismatched allografts are uncertain. We aimed to determine the effect of HLA-DQ mismatches on renal allograft outcomes.Design, setting, participants, & measurementsUsing data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the association between HLA-DQ mismatches and acute rejections in primary live and deceased donor kidney transplant recipients between 2004 and 2012 using adjusted Cox regression models.ResultsOf the 788 recipients followed for a median of 2.8 years (resulting in 2891 person-years), 321 (40.7%) and 467 (59.3%) received zero and one or two HLA-DQ mismatched kidneys, respectively. Compared with recipients who have received zero HLA-DQ mismatched kidneys, those who have received one or two HLA-DQ mismatched kidneys experienced greater numbers of any rejection (50 of 321 versus 117 of 467; P<0.01), late rejections (occurring >6 months post-transplant; 8 of 321 versus 27 of 467; P=0.03), and antibody-mediated rejections (AMRs; 12 of 321 versus 38 of 467; P=0.01). Compared with recipients of zero HLA-DQ mismatched kidneys, the adjusted hazard ratios for any and late rejections in recipients who had received one or two HLA-DQ mismatched kidneys were 1.54 (95% confidence interval [95% CI], 1.08 to 2.19) and 2.85 (95% CI, 1.05 to 7.75), respectively. HLA-DR was an effect modifier between HLA-DQ mismatches and AMR (P value for interaction =0.02), such that the association between HLA-DQ mismatches and AMR was statistically significant in those who have received one or two HLA-DR mismatched kidneys, with adjusted hazard ratio of 2.50 (95% CI, 1.05 to 5.94).ConclusionsHLA-DQ mismatches are associated with acute rejection, independent of HLA-ABDR mismatches and initial immunosuppression. Clinicians should be aware of the potential importance of HLA-DQ matching in the assessment of immunologic risk in kidney transplant recipients.

Dataset Information

Associations between HVEM/LIGHT/BTLA/CD160 polymorphisms and the occurrence of antibody-mediate rejection in renal transplant recipients.

Publications

Associations between <i>HVEM/LIGHT/BTLA/CD160</i> polymorphisms and the occurrence of antibody-mediate rejection in renal transplant recipients.

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