Increased Proportion of Circulating T Follicular Helper Cells and Serum Levels of IL-21 in Antibody-Mediated Rejection of Renal Allograft.

Abstract

Introduction: Antibody-mediated rejection (AMR) is one of the major obstacles to successful kidney transplantation. The T helper cell subset that plays a key role in the activation of B-lymphocytes and antibody production is T follicular helper (Tfh) cell. Therefore, we aimed to compare the percentage of Tfh cells and the serum level of interleukin 21 (IL-21), mainly secreted by this subset, in patients with AMR and stable recipients.

Methods: Peripheral blood samples were taken from 30 patients diagnosed with AMR and 30 stable kidney transplant recipients as well as 10 age- and sex-matched healthy individuals. The percentage of circulating Tfh cells (TCD4+CXCR5+PD1+) and the level of IL-21 were studied by flow cytometry and ELISA techniques, respectively.  Results. The proportion of cTfh cells among circulating TCD4+ cells in AMR patients was markedly elevated compared to the other groups (P < .0001). It was also higher in stable recipients than in healthy controls (P < .0001). The serum level of IL-21 was increased in AMR patients compared to stable recipients (P = .03) and healthy participants (P = .02). In addition, there was a significant negative correlation between cTfh percentage and the estimated glomerular filtration rate (eGFR) in transplanted patients (P = .001). Moreover, the AUC of cTfh cells in AMR diagnosis was 0.83 [95% CI 0.73-0.93 (P < .0001)].

Conclusion: In AMR patients, cTfh cell percentage and IL-21 levels were significantly increased. The significant association between cTfh % and eGFR, with an AUC of 0.83, indicates its potential as a diagnostic and prognostic marker in AMR.