Therapeutic potential of targeting Tfr/Tfh cell balance by low-dose-IL-2 in active SLE: a post hoc analysis from a double-blind RCT study

Abstract Objective To investigate the regulation of T follicular regulatory (Tfr) and (Tfh) cell subtypes by low-dose IL-2 in systemic lupus erythematosus (SLE) a randomized, double-blind, placebo-controlled clinical trial. Methods A post hoc analysis was performed randomized cohort SLE patients (n=60) receiving therapy (n=30) or placebo (n=30), along with standard care treatment. The primary endpoint attainment responder index-4 (SRI-4) at week 12 Twenty-three healthy controls were enrolled for subset detection same time as t-stochastic neighbor embedding (tSNE) CD4 subsets based on immune cells flow cytometry markers to distinguish Tfh, Tfh1, Tfh2, Tfh17, Tfr subsets. Results Compared HC, frequency (CXCR5 + PD-1 low Treg CXCR5 high Treg) significantly reduced, while pro-inflammatory Tfh increased SLE. imbalanced associated several pathogenic factors (anti-dsDNA antibodies (r=0.309, P=0.027) serum IL-17 (r=0.328, P=0.021)) Disease Activity Index (SLEDAI) score (r=0.273, P=0.052). Decreased Treg/Tfh Treg/Tfh17 both immunoglobulin M (IgM) (r=−0.448, P=0.002 r=−0.336, P=0.024, respectively). Efficacy restored Tfr/Tfh balance. Conclusion These data support hypothesis that promotion is decreased disease activities can recover Trial registration number ClinicalTrials.gov Registries ( NCT02465580 ).