Genetic polymorphisms in the immune response: A focus on kidney transplantation

Stojanova, Jana; Pouché, Lucie; Picard, Nicolas

doi:10.1016/j.clinbiochem.2015.07.016

Cited by 9 publications

(12 citation statements)

References 117 publications

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“…Kidney transplantation is currently the best therapy option for patients with end-stage renal disease [ 3 ]. The success of kidney transplantation depends on many factors, such as age, ethnicity, human leukocyte (HLA)-mismatch, and ischemia time [ 4 ]. Despite growing experience with kidney transplantation throughout the past decades, the incidence of severe complications remains high, which reflects high interindividual variability in the postoperative course of disease [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration

Rump

Rahmel

Rustige

et al. 2020

Cells

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Major complications after kidney transplantation are graft rejection and cytomegalovirus (CMV) infection, which are related to T-cell function, which depends on aquaporin 3 (AQP3) expression. The impact of the AQP3 A(−1431)G promoter polymorphism in kidney transplant recipients was unelucidated and we explored the effect of AQP3 polymorphism on immune cell function and its association with graft rejection and CMV infection in 237 adult patients within 12 months after transplantation. AQP3 promoter polymorphism was molecular and functional characterized. Kaplan–Meier plots evaluated the relationship between genotypes and the incidence of CMV infection and graft rejection. AQP3 A(−1431)G A-allele was associated with enhanced immune cell migration and AQP3 expression in T-cells. The incidences of rejection were 45.4% for the A-allele and 27.1% for G-allele carriers (p = 0.005) and the A-allele was a strong risk factor (hazard ratio (HR): 1.95; 95% CI: 1.216 to 3.127; p = 0.006). The incidences for CMV infection were 21% for A-allele and 35% for G-allele carriers (p = 0.013) and G-allele was an independent risk factor (p = 0.023), with a doubled risk for CMV infection (HR: 1.9; 95% CI: 1.154 to 3.128; p = 0.012). Hence, A-allele confers more resistance against CMV infection, but susceptibility to graft rejection mediated by T-cells. Thus, AQP3-genotype adapted management of immunosuppression and antiviral prophylaxis after kidney transplantation seems prudent.

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Section: Introductionmentioning

confidence: 99%

The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration

Rump

Rahmel

Rustige

et al. 2020

Cells

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“…Mediators of the immune response, such as costimulatory molecules, cytokines and receptors, innate immune system and others, have been proposed to play important roles in immunologic tolerance of organ solid transplantation. Polymorphisms in genes involved in the immune response have been proposed as predictive factors of clinical graft outcomes in kidney transplantation (Stojanova, Pouché, Picard, 2016). This review explored the pharmacogenomic studies focused on immune response-related genes in kidney transplantation and the main clinical outcomes.…”

Section: Pharmacogenomics Of Mycophenolic Acid In Kidney Transplantat...mentioning

confidence: 99%

“…T cell activation is modulated by co-stimulatory molecules, including CD28 and inducible costimulatory (ICOS), as well as by negative regulators, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PDCD1, PD-1). Variants in genes encoding these molecules were proposed to contribute to acute rejection and other allograft outcomes (Stojanova, Pouché, Picard, 2016).…”

Section: Genes Related To T Cell Activationmentioning

confidence: 99%

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Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes

Hirata

Genvigir

Hirata

et al. 2022

Braz. J. Pharm. Sci.

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Mycophenolic acid (MPA) inhibits IMPDH, involved in the guanosine nucleotides synthesis, and prevents DNA replication in immune cells. The repression of cell and humoral immunity by MPA induces allograft tolerance preventing acute rejection in solid organ transplantation. MPA is an effective and safe drug, but genetic and non-genetic factors have been implicated in the interindividual variability of drug response. Several studies have shown the impact of variants of pharmacokinetics or pharmacodynamics-related genes on MPA response in kidney transplantation. This review explored further the influence of genes involved in the immune response on clinical outcomes of kidney recipients on short-or long-term MPA treatment. Variants in genes related to T cell activation (CD28, CTL4, ICOS, PDPC1), pro-inflammatory cytokines (IL2, IL6, IL12A, IL12B, TNF, IFNG), immunomodulatory cytokines (IL4, IL10, TGFB1), and innate immune response (CD14, TLR2, TLR4) were shown to be associated with increased risk of acute rejection, graft function or survival, chronic graft nephropathy, viral infections or MPA-induced myelotoxicity. Some of the significant pharmacogenetic associations were confirmed by meta-analyses of kidney transplantation. These findings are suggestive that variants in immune response-related genes contribute to the variability of MPA response, and have potential application as biomarkers of acute rejection in kidney transplantation.

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“…In most studies, AR was the phenotype investigated. For more than 2 decades studies reported significant associations between AR and individual candidate variants, 3,4 though other outcomes were studied. 5 In most cases the p-values were modest, as were the effect sizes.…”

Section: Introductionmentioning

confidence: 99%

Concepts of Genomics in Kidney Transplantation

et al. 2017

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Purpose of review Identification of genetic variants to aid in individualized treatment of solid organ allograft recipients would improve graft survival. We will review the current state of knowledge for associations of variants with transplant outcomes. Recent findings Many studies have yet to exhibit robust and reproducible results, however, pharmacogenomic studies focusing on cytochrome P450 (CYP) enzymes, transporters and HLA variants have shown strong associations with outcomes and have relevance towards drugs used in transplant. Genome wide association study data for the immunosuppressant tacrolimus have identified multiple variants in the CYP3A5 gene associated with trough concentrations. Additionally, APOL1 variants had been shown to confer risk to the development of end stage renal disease in African Americans. Summary The field is rapidly evolving and new technology such as next generation sequencing, along with larger cohorts, will soon be commonly applied in transplantation to understand genetic association with outcomes and personalized medicine.

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Genetic polymorphisms in the immune response: A focus on kidney transplantation

Cited by 9 publications

References 117 publications

The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration

The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration

Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes

Concepts of Genomics in Kidney Transplantation

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