Circulating follicular helper T cells are associated with mortality in sepsis

Introduction B-cell dysfunction is a key component of immune derangement in sepsis. Follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells play critical roles in B cell maturation and differentiation. The aim of this study was to investigate whether the balance of circulating Tfh subsets (Tfh1, Tfh2, Tfh17, and Tfh17.1) and Tfr cells is altered in sepsis and evaluate their associations with B cell subsets and 28-day mortality. Methods Peripheral blood Tfh, Tfr, and B cell subsets were measured by flow cytometry in 69 healthy controls and 123 patients with sepsis on day 1 and reassessed on day 7. Results Compared with healthy controls, patients with sepsis showed significant reductions in the numbers of Tfh cell subsets and Tfr cells. Tfh subset composition was altered, with a decreased proportion of Tfh17.1 cells and a relatively increased proportion of Tfh17 cells. Tfr frequency was significantly lower, and Tfh/Tfr ratio was markedly elevated. Prognostic analysis showed that non-survivors had a lower Tfh cell percentage than survivors on day 1. Tfh percentage ≥ 17.05% was independently associated with lower 28-day mortality (OR [95% CI]: 0.331 [0.127, 0.861], P = 0.023). By day 7, absolute counts of Tfh cell subsets and Tfr cells were significantly lower in non-survivors than in survivors. Spearman’s partial correlation analysis indicated that the numbers of Tfh cell subsets and Tfr cells were positively correlated with memory or CD5 + B cells, except for Tfh1. Discussion Tfh cell subsets in sepsis are redistributed, with an elevated Tfh/Tfr ratio. A Tfh (%) ≥ 17.05% was independently associated with lower 28-day mortality. These findings provide new insights into immune dysregulation in sepsis.