Introduction: Antibody (Ab) mediated rejection is responsible for 30-50% of renal graft failures. Follicular helper T cells (Tfh) are required for the differentiation of B cells into plasma cells and for the efficient production of Ab. Recently, circulating Tfh (cTfh) have been identified in peripheral blood; this facilitates the study of cTfh as potential biomarker in renal transplantation (Tx). With this background, the aims of our study are: (1) to show the capacity of cTfh to differentiate B cells into plasma cells and produce Ab, (2) to study cTfh in chronic kidney disease patients preTx, (3) to follow up variations in cTfh postTx and (4) to correlate differences in cTfh distribution with graft outcome.

Methods: We isolated PBMCs at preTx and up to 1 year postTx from a prospective cohort of renal Tx recipients (n=163). We analyzed cTfh by flow cytometry as CD4+CXCR5+ or CD4+CXCR5+CCR7lowPD1high. cTfh were cocultured with B cells to interrogate their capacity to stimulate conversion to plasmablasts and Ab production.

Results: We showed that when co-cultured with cTfh, B cells differentiated into plasmablasts and produce IgG. PreTx, cTfh decreased in patients who had received dialysis (p<0.01). Conversely, cTfh were increased in retransplanted patients, in those with previous blood transfusions and in patients with anti-HLA Ab preTx (sensitized patients) (p<0.05, all comparisons). During follow-up, cTfh decreased a week after Tx in patients who received thymoglobulin as induction therapy (p<0.05) and started to increase three months after Tx. Patients who received thymoglobulin tripled their cTfh six months postTx. Basiliximab treatment did not deplete cTfh. We explored the utility of cTfh as biomarker in renal Tx and found that cTfh were increased preTx in patients who will develop de novo anti-HLA Ab and in patients who will have a rejection compared to patients who will not do so (p<0.05, both).

Conclusions: There are differences in cTfh between patients, mainly related to HLA sensitization. PreTx cTfh measurement could be a useful non-invasive biomarker, enabling us to predict renal graft outcome and, therefore, to take early preventive measures to avoid graft failure.

CITATION INFORMATION: Laguna-Goya R., Utrero-Rico A., Cano-Romero F., Gómez-Massa E., Arroyo D., Auñon-Rubio P., Sevillano-Prieto A., Castro-Panete M., Andrés A., Paz-Artal E. Circulating Follicular Helper T Cells (cTfh) in Renal Transplantation: Utility as Rejection Biomarker Am J Transplant. 2017;17 (suppl 3).

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