To investigate the regulation of T follicular regulatory (Tfr) and T follicular (Tfh) cell subtypes by low-dose IL-2 in systemic lupus erythematosus (SLE) in a randomized, double-blind, placebo-controlled clinical trial.
A post hoc analysis was performed in a randomized cohort of SLE patients (n=60) receiving low-dose IL-2 therapy (n=30) or placebo (n=30), along with the standard of care treatment. The primary endpoint was the attainment of SLE responder index-4 (SRI-4) at week 12 in the trial. Twenty-three healthy controls were enrolled for T cell subset detection at the same time as the trial. The t-stochastic neighbor embedding (tSNE) analysis of CD4 T subsets based on immune cells flow cytometry markers was performed to distinguish Tfh, Tfh1, Tfh2, Tfh17, and Tfr cell subsets.
Compared with HC, the frequency of Tfr (CXCR5PD-1 Treg and CXCR5PD-1 Treg) cells was significantly reduced, while the pro-inflammatory Tfh cells were increased in patients with SLE. The imbalanced Tfh cell was associated with several pathogenic factors (anti-dsDNA antibodies (r=0.309, P=0.027) and serum IL-17 (r=0.328, P=0.021)) and SLE Disease Activity Index (SLEDAI) score (r=0.273, P=0.052). Decreased CXCR5PD-1 Treg/Tfh and CXCR5PD-1 Treg/Tfh17 were both associated with increased immunoglobulin M (IgM) (r=-0.448, P=0.002 and r=-0.336, P=0.024, respectively). Efficacy of low-dose IL-2 therapy was associated with a restored Tfr/Tfh cell balance.
These data support the hypothesis that promotion of Tfr is associated with decreased disease activities and that low-dose IL-2 therapy can recover Tfr/Tfh immune balance.
ClinicalTrials.gov Registries ( NCT02465580 ).
About The Expert
Miao Miao
Xian Xiao
Jiayi Tian
Yunzhi Zhufeng
Ruiling Feng
Ruijun Zhang
Jiali Chen
Xiaoying Zhang
Bo Huang
Yuebo Jin
Xiaolin Sun
Jing He
Zhanguo Li
References
PubMed