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

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

doi:10.3389/fphar.2019.01686

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

Front Pharmacol. 2020 Feb 20:10:1686. doi: 10.3389/fphar.2019.01686. eCollection 2019.

Authors

Rong Hu¹, Daniel T Barratt¹, Janet K Coller¹, Benedetta C Sallustio^{1

2}, Andrew A Somogyi^{1

3}

Affiliations

¹ Discipline of Pharmacology, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
² Department of Clinical Pharmacology, The Queen Elizabeth Hospital, Adelaide, SA, Australia.
³ Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, SA, Australia.

Abstract

Background: Innate 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.

Objective: To 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.

Methods: This 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.

Results: A 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.

Conclusions: This 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.

Keywords: IL6 -6331; acute rejection; immune genetics; kidney transplantation; tacrolimus.