No Major Effect of Innate Immune Genetics on Acute Kidney Rejection in the First 2 Weeks Post-Transplantation.

Rong Hu,Andrew A Somogyi,Janet K Coller,Benedetta C Sallustio,Daniel T Barratt

doi:10.3389/fphar.2019.01686

Rong Hu, Andrew A Somogyi + Show 3 more

Open Access

https://doi.org/10.3389/fphar.2019.01686

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Abstract

BackgroundInnate immunity contributes to acute rejection after kidney transplantation. Genetic polymorphisms affecting innate immunity may therefore influence patients’ risk of rejection. IL2 -330T > G, IL10 -1082G > A, -819C > T, and -592C > A, and TNF -308G > A are not associated with acute rejection incidence in Caucasian kidney transplant recipients receiving a calcineurin inhibitor, ciclosporin or tacrolimus (TAC). However, other important innate immune genetic polymorphisms have not yet been extensively studied in recipients and donors. In addition, innate immunogenetics have not been investigated in kidney transplant cohorts receiving only TAC as the calcineurin inhibitor.ObjectiveTo investigate the effect of recipient and donor CASP1, CRP, IL1B, IL2, IL6, IL6R, IL10, MYD88, TGFB, TLR2, TLR4, and TNF genetics on acute kidney rejection in the first 2 weeks post-transplant in TAC-treated kidney transplant recipients.MethodsThis study included 154 kidney transplant recipients and 81 donors successfully genotyped for 17 polymorphisms in these genes. All recipients were under triple immunosuppressant therapy of TAC, mycophenolate mofetil, and prednisolone. Recipient and donor genotype differences in acute rejection incidence within the first 2 weeks post-transplantation were assessed by logistic regression, adjusting for induction therapy, human leukocyte antigen mismatches, kidney transplant number, living donor, and peak panel-reactive antibody scores.ResultsA trend (Cochran-Armitage P = 0.031) of increasing acute rejection incidence was observed from recipient IL6 -6331 T/T (18%) to T/C (25%) to C/C (46%) genotype [C/C versus T/T odds ratio (95% confidence interval) = 6.6 (1.7 to 25.8) (point-wise P = 0.017)]. However, no genotype differences were significant after Bonferroni correction for multiple comparisons.ConclusionsThis study did not detect any statistically significant effects of recipient or donor innate immune genetics on acute rejection incidence in the first 2 weeks post-transplantation. However, the sample size was small, and future larger studies or meta-analyses are required to demonstrate conclusively if innate immune genetics such as IL6 influence the risk of acute rejection after kidney transplantation.

Highlights

Acute rejection is the major short-term challenge following kidney transplantation and it increases long-term graft loss (McDonald et al, 2007)
To bridge these research gaps, this study aimed to explore the impact of recipient and donor CASP1, C-reactive protein (CRP), IL1B, IL2, IL6, IL6R, IL10, MYD88, TGFB, TLR2, TLR4, and TNF genotypes on biopsy-proven acute rejection (BPAR) incidence in a cohort of predominantly Caucasian kidney transplant recipients treated with TAC as the only calcineurin inhibitor (CNI) (Hu et al, 2018; Hu et al, 2019a; Hu et al, 2019b)
Six recipients each received a kidney from three deceased donors, these three donors were counted only once for Hardy-Weinberg Equilibrium (HWE) tests but were treated independently for logistic regression analyses

Summary

Introduction

Acute rejection is the major short-term challenge following kidney transplantation and it increases long-term graft loss (McDonald et al, 2007). Caspase 1 (encoded by CASP1) is an inflammatory response initiator and converts pro-IL-1b into mature IL-1b (Kostura et al, 1989; Thornberry et al, 1992). These pro-inflammatory mediators can assist T-cell activation, proliferation, and differentiation, and intensify kidney tissue damage (Watson et al, 1980; Nankivell and Alexander, 2010; Anders and Schaefer, 2014). IL2 -330T > G, IL10 -1082G > A, -819C > T, and -592C > A, and TNF -308G > A are not associated with acute rejection incidence in Caucasian kidney transplant recipients receiving a calcineurin inhibitor, ciclosporin or tacrolimus (TAC). Innate immunogenetics have not been investigated in kidney transplant cohorts receiving only TAC as the calcineurin inhibitor

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