This preprint is under consideration at Arthritis Research & Therapy. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
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
Jing He
Peking University People's Hospital
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Objective: 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.
Methods: 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 standard of care treatment. The primary end point was attainment of SLE responder index-4 (SRI-4) at week 12 in the trial. Twenty three healthy controls were enrolled for T cell subsets detection at the same time with 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.
Results: Compared with HC, the frequency of Tfr (CXCR5+PD-1lowTreg and CXCR5+PD-1highTreg) 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-1lowTreg/Tfh and CXCR5+PD-1lowTreg/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.
Conclusion: These data supports the hypothesis that promotion of Tfr associated with decreased disease activities, and that low-dose IL-2 therapy can recover Tfr/Tfh immune balance.
Trial registration number ClinicalTrials.gov Registries (NCT02465580).
Keywords
systemic lupus erythematosus, T follicular helper cell, T follicular regulatory cell, low-dose interleukin-2
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 05 Jan, 2021
No community comments so far
Editor assigned
On 20 Dec, 2020
Submission checks complete
On 20 Dec, 2020
Editor invited
On 20 Dec, 2020
First submitted
On 17 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Rheumatology
Learn more about our company.
This preprint is under consideration at Arthritis Research & Therapy. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
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
Jing He
Peking University People's Hospital
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 05 Jan, 2021
No community comments so far
Editor assigned
On 20 Dec, 2020
Submission checks complete
On 20 Dec, 2020
Editor invited
On 20 Dec, 2020
First submitted
On 17 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Rheumatology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Objective: 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.
Methods: 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 standard of care treatment. The primary end point was attainment of SLE responder index-4 (SRI-4) at week 12 in the trial. Twenty three healthy controls were enrolled for T cell subsets detection at the same time with 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.
Results: Compared with HC, the frequency of Tfr (CXCR5+PD-1lowTreg and CXCR5+PD-1highTreg) 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-1lowTreg/Tfh and CXCR5+PD-1lowTreg/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.
Conclusion: These data supports the hypothesis that promotion of Tfr associated with decreased disease activities, and that low-dose IL-2 therapy can recover Tfr/Tfh immune balance.
Trial registration number ClinicalTrials.gov Registries (NCT02465580).
Figure 1
Figure 2
Figure 3
Figure 4