Background/Purpose: Systemic lupus erythematosus (SLE) is a potentially fatal autoimmune disease. Regulatory T (Treg) cells and T helper type 17 (Th17) cells play opposite roles in immune tolerance and autoimmune diseases. It was reported previously that elevated Th17 and/or decreased Treg cells caused an imbalance of Treg/Th17 in SLE. Since low-dose IL-2 can selectively stimulate the differentiation of CD4+Treg cells and rapamycin can promote the proliferation of Treg cells and inhibits differentiation of Th17 cells, the combined treatment of the low-dose IL-2 and rapamycin may increase the remission rate of SLE.

Methods: Sixty-six refractory SLE patients (53 women and 3 men), with an average course of 74.22±40.91 months and average age of 33.10±11.72 years, were enrolled. They fulfilled the 1997 ACR criteria and had been treating with glucocorticoid and immunosuppressant for more than one year, but had not yet reached the disease remission. The standard for remission is defined as meeting all the following conditions: sustained remission of clinical symptoms, no organ damage indication, normal inflammatory index and normal immune function. The eligible patients were given IL-2 and rapamycin in combination with conventional therapy. At 0, 6, 12, 24 week respectively after medication, the absolute numbers of Th17 cells and Treg cells in blood were examined by flow cytometry. Also, the clinical symptoms, blood routine, urine routine, ESR, the dosage of corticosteroids and immunosuppressant, or the remission rate was registered respectively.

Results: As compared with healthy controls, the absolute number of Treg cells in the patients with refractory SLE significantly decreased, whereas that of Th17 cells did not increase clearly. At 24 week after treatment with low-dose IL-2 combined with rapamycin, 36.0% of patients with refractory SLE achieved remission, accompanying increase in the absolute numbers of peripheral Treg cells from a median of 17.08 cells/µl (at week 0) to 28.16 cells/µl (at week 24) (P=0.002). Accordingly, he ratio of Th17/Treg cells showed a reduction from a median of 0.87 at week 0 to 0.31 at week 24 (P=0.019), indicating a restored balance of them. No significant difference was observed in the absolute numbers of Th17 after combined treatment. At week 24, the mean dosage of prednisone used in refractory SLE patients was decreased from 17.19 mg/d to 9.11 mg/d. And the categories of immunosuppressant used were also reduced (P<0.05).

Conclusion: Our findings indicate that refractory SLE is associated with the decreased absolute number of Treg cells but not increased Th17 cells in blood. Low-dose IL-2 combined with rapamycin treatment can restore the balance of Th17 and Treg cells in refractory SLE due to the significant increase in Treg cells. This therapy can induce higher remission rate of the patients after 24-week treatment and reduce the usage of glucocorticoid and immunosuppressant.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/low-dose-il-2-combined-with-rapamycin-efficiently-promotes-remission-of-refractory-systemic-lupus-erythematosus/