{Reference Type}: Journal Article
{Title}: 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.
{Author}: Miao M;Xiao X;Tian J;Zhufeng Y;Feng R;Zhang R;Chen J;Zhang X;Huang B;Jin Y;Sun X;He J;Li Z;
{Journal}: Arthritis Res Ther
{Volume}: 23
{Issue}: 1
{Year}: 06 2021 11
{Factor}: 5.606
{DOI}: 10.1186/s13075-021-02535-6
{Abstract}: 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.<BR>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.<BR>Compared with HC, the frequency of Tfr (CXCR5+PD-1low Treg and CXCR5+PD-1high 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 CXCR5+PD-1low Treg/Tfh and CXCR5+PD-1low 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.<BR>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.<BR>ClinicalTrials.gov Registries ( NCT02465580 ).