Impact of Proinflammatory Cytokine Gene Polymorphisms and Circulating CD3 on Long-Term Renal Allograft Outcome in Egyptian Patients

Immunol Invest. 2021 Nov;50(8):1072-1084. doi: 10.1080/08820139.2020.1804398. Epub 2020 Aug 17.

Abstract

The extant study aimed to explore the influence of two cytokines TNF-α - 308 and IFN-γ + 874 gene polymorphism on development of renal transplant rejection and to investigate the feasibility of Th1 cytotoxic immune reaction (CD3). It includes 152 kidney recipients were divided into two subgroups: 76 stable graft functions (SGF) and 76 allograft dysfunctions (AD) compared with 56 healthy individuals as control group. TNF-α - 308 G > A and IFN-γ + 874 A > T genetic polymorphisms were characterized using ARMS-PCR technique. CD3 protein expression was measured using ELISA Kit. The effect on transplant outcome was analyzed where, statistically significant differences of TNF-a-308 G/A were observed between AD group when compared to SGF group (OR = 0.296, 95% CI = 0.091-0.965, p = .031) in AG genotype (intermediate producer genotype). Also, AD group displayed a statistically significant increase of IFN-γ + 874 TT (high producer genotype) when compared to SGF group (OR = 0.290, 95% CI = 0.127-0.665, p = .003). The expression of CD3+ T lymphocytes in recipients with allograft dysfunction was statistically higher than that with stable allograft function and control groups (732 ± 76, 235 ± 51 and 442 ± 50) respectively and (p ≤ 0.001). In conclusion, IFN-γ + 874 T and TNF-α - 308 A alleles are risk alleles for renal transplant rejection and these two single nucleotide polymorphisms (SNPs) may be implicated in the tendency of rejection after renal transplantation. CD3 may be used as non-invasive biomarker in monitoring of rejection and avoid exposing patients for biopsy risks and sampling error.

Keywords: Kidney transplantation; allograft dysfunction; cd3+ T lymphocytes; ifn-γ +874 A>T; polymorphisms; tnf-α −308 G>A.

MeSH terms

  • Allografts
  • Cytokines / genetics
  • Egypt
  • Genotype
  • Graft Rejection / genetics
  • Humans
  • Kidney
  • Kidney Transplantation*
  • Polymorphism, Single Nucleotide

Substances

  • Cytokines