Restoring T-helper 17 cell/regulatory T-cell balance and decreasing disease activity by rapamycin and all-trans retinoic acid in patients with systemic lupus erythematosus

Lupus. 2019 Oct;28(12):1397-1406. doi: 10.1177/0961203319877239. Epub 2019 Sep 24.

Abstract

Objective: This study aimed to investigate the effect of rapamycin (RAPA) alone or in combination with all-trans retinoic acid (ATRA) on the T-helper 17 (Th17) cell/regulatory T-cell (Treg) balance in patients with systemic lupus erythematosus (SLE) and to evaluate the clinical efficacy.

Methods: Seventy patients with SLE were enrolled. They were randomly and equally divided into RAPA and RAPA + ATRA groups. The number of Th17 and Treg cells was measured by flow cytometry before and after treatment for 6, 12 and 24 weeks. The SLE Disease Activity Index (SLEDAI) score and the prednisone dose before and after treatment were used to evaluate the efficacy between the two groups.

Results: In both groups, at different time points after treatment, the number of Th17 cells (p = 0.003) and Th17/Treg ratio (p = 0.044) reduced, while the number of Treg cells (p = 0.574) tended to increase. The SLEDAI score and the dose of prednisone decreased significantly (p < 0.001). There was no significant difference in the number of Th17 cells (p = 0.089), Treg cells (p = 0.059), Th17/Treg ratio (p = 0.580), SLEDAI score (p = 0.127) and the dose of prednisone (p = 0.329) between the two groups.

Conclusion: Disease activity in SLE patients reduced with RAPA alone or in conjunction with ATRA, reducing glucocorticoid requirement. One of its mechanisms of action may be regulating the Th17/Treg cell balance, which provides a new model for the pathogenesis and potential treatment of SLE.

Keywords: Systemic lupus erythematosus; all-trans retinoic acid; helper T cells 17; rapamycin; regulatory T cells.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / pathology
  • Male
  • Middle Aged
  • Prednisone / therapeutic use
  • Sirolimus / adverse effects
  • Sirolimus / pharmacology
  • Sirolimus / therapeutic use*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / drug effects*
  • Th17 Cells / metabolism
  • Tretinoin / adverse effects
  • Tretinoin / pharmacology
  • Tretinoin / therapeutic use*

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Tretinoin
  • Prednisone
  • Sirolimus