Background Refractory system lupus erythematosus (SLE) still relies on aggressive treatment with high-dose glucocorticoids and immunosuppressive agents,but a significant proportion of patients persist with activity or relapse and show serious side-effects by the treatment.However, the imbalance of Th17 cells and regulatory T (Treg) cells in peripheral blood of patients with SLE may be an important factor in the pathogenesis of SLE.Because low-dose IL-2 can selectively enhance Treg function while avoiding the activation of effector T cells and rapamycin can promote the proliferation of Treg cells1–2,the combination of the low-dose IL-2 and rapamycin has been considered to treat refractory SLE for the purpose of remission.
Objectives To observe the effect of low-dose IL-2 combined with rapamycin on the balance of Th17/Treg cells in patients with refractory SLE.
Methods Eighty-two refractory SLE patients (80 women and 2 men),with a mean duration of 72.41±37.52 months and mean age of 36.22±12.48 years, were enrolled.They are in line with the standard of ACR in 1997,who are treated with glucocorticoid and immunosuppressant for more than one year, but the subjects continues to rise to a peak.After the eligible patients are given IL-2 and rapamycin in combination therapy with conventional therapy at 0, 6, 12, 24 week respectively after medication.The clinical symptoms, blood routine, urine routine, ESR, Th17 cells, Treg cells, Th17/Treg cells and the dosage of corticosteroids and immunosuppressant are registered one by one.
Results At 24 week after treatment,28.9% patients with refractory SLE were relieved.Low-dose IL-2 combined with rapamycin leaded to an increase in the absolute counts of Treg cells in refractory SLE patients,from a median of 12.98 cells/ul (at week 0) to 22.1 cells/ul (at week 24) (P=0.002).The ratio of Th17/Treg cells shows a reduction from a median of 0.44 at week 0 to 0.29 at week 24 (P=0.029).No significant difference was observed in the absolute counts of Th17 after combined treatment.At week 24, the mean dosage of prednisone which refractory SLE patients were receiving decreased from 17.20 mg/d to 8.87 mg/d.And the categories of DMARDs use were also reduced (P<0.05).
Conclusions Our results suggest that refractory SLE is major associated with the decreased number of Treg but not that of Th17.The Th17 and Treg cells in the peripheral blood of patients with refractory SLE tends to balance due to the significantly increase the number of Treg cells after low-dose IL-2 combined with rapamycin treatment.Low-dose IL-2 combined with rapamycin treatment can reduce the dosage of glucocorticoid and DMARDs.
Liao, W.,Lin, J. X. & Leonard,W. J.Interleukin-2 at the crossroads of effector responses,tolerance,and immunotherapy.Immunity 38,13–25 (2013).
Tomasoni R, Basso V, Pilipow K, etal.Rapamycin-sensitive signals control RCR/CD28-driven Ifng,I14and Foxp3 transcription and promoter region methylation.Eur J Immunol,2011,41:2086–2096.
Disclosure of Interest None declared
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