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Sirolimus selectively increases circulating Treg cell numbers and restores the Th17/Treg balance in rheumatoid arthritis patients with low disease activity or in DAS28 remission who previously received conventional disease-modifying anti-rheumatic drugs

1, 2, 3, 4, 5, 6, 7, 8, 9, 10

  1. Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
  2. Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
  3. Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
  4. Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
  5. Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
  6. Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
  7. Department of Geriatric Haematology, Chinese PLA General Hospital, Beijing, China.
  8. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA.
  9. Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan, China. snwch@sina.com
  10. Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan, China.

CER11997 Submission on line
Full Papers

Rheumatology Article

 

Abstract

OBJECTIVES:
Regulatory T (Treg) cells are crucial players in the prevention of autoimmunity. Mechanistic target of rapamycin (mTOR) signalling negatively controls the development and function of Treg cells. The aim of the present study was to evaluate the effects of rapamycin, under the generic name sirolimus, on CD4+CD25+FoxP3+ Treg cells in rheumatoid arthritis (RA) patients with low disease activity or in DAS28 remission.
METHODS:
Fifty-five RA patients and 60 healthy controls were enrolled in this study. All patients had previously received conventional disease-modifying anti-rheumatic drugs (DMARDs) and were considered to have a low DAS28 score (≤3.2). Peripheral blood samples and clinical information were obtained at baseline and following 6 and 12 weeks of sirolimus treatment, or after 12 weeks of conventional treatment. Peripheral blood samples were also obtained from the healthy controls. The circulating levels of lymphocyte subpopulations were assessed by flow cytometry.
RESULTS:
Thirty-five patients received sirolimus and 20 patients continued treatment with conventional DMARDs. The absolute counts and proportions of CD4+CD25+FoxP3+ Treg cells were significantly lower in all RA patients with DAS28 ≤ 3.2 as compared with those in healthy controls. By contrast, the difference in circulating Th17 cell numbers was not significant. Sirolimus administration resulted in elevations in circulating Treg cell numbers and significant reductions in the Th17/Treg cell ratio, whereas the circulating level of Treg cells and the Th17/Treg cell ratio in patients under conventional treatment both showed a tendency of reduction. Furthermore, a greater proportion of patients under sirolimus treatment achieved DAS28-based remission at 12 weeks.
CONCLUSIONS:
Sirolimus can favourably expand Treg cells in RA patients with DAS28 ≤3.2, consequently restoring a healthy balance of Th17/Treg cells, which might improve the likelihood of long-term and sustained clinical remission and reduce the probability of disease flare-ups in RA.

PMID: 31074719 [PubMed]

Received: 16/12/2018 - Accepted : 05/03/2019 - In Press: 29/04/2019