Increased Plasma Angiogenin Level is Associated and May Contribute to Decreased T-Cell Zeta-Chain Expression in Hemodialysis Patients

Abstract

Hemodialysis (HD) patients are characterized by impaired T-cell function at least in part because of T-cell zeta-chain downregulation due to inflammation. Angiogenin responds as an acute phase reactant, is increased in HD patients, suppresses T-cell function and increased angiogenin level is co-localized with T-cell zeta-chain downregulation in various pathologies. Angiogenin can inhibit translation of proteins, which lack internal ribosomal entry sites in the corresponding mRNAs. In this study, the possible effect of angiogenin on T-cell zeta-chain downregulation was evaluated. Thirty HD patients and 21 healthy volunteers participated. T-cell zeta-chain expression was assessed with flow cytometry, plasma angiogenin and serum IL-6 with ELISA and serum C-reactive protein with an immunoturbidimetric method. Two available software tools were used for predicting the presence or not of internal ribosomal entry sites in T-cell zeta-chain mRNA sequence. In silico analysis of T-cell zeta-chain mRNA sequence failed to reveal the presence of internal ribosomal entry sites. T-cell zeta-chain expression was lower in HD patients than in healthy volunteers (1.86 +/- 0.63 vs. 4.73 +/- 3.22). In HD patients, C-reactive protein as well as IL-6 were higher than in healthy volunteers (10.04 +/- 15.13mg/L vs. 3.43 +/- 0.98mg/L and 15.06 +/- 13.08pg/mL vs. 2.11 +/- 2.10pg/mL respectively). Angiogenin was higher in HD patients than in healthy volunteers (483.20 +/- 154.07ng/mL vs. 259.98 +/- 64.15ng/mL). Neither C-reactive protein, nor IL-6 was associated with angiogenin or T-cell zeta-chain expression. Angiogenin concentration was negatively related to the expression of T-cell zeta-chain (r=0.410, P=0.025). Increased angiogenin may contribute to decreased T-cell zeta-chain expression in HD patients.