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

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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.