Background The concept of Mixed Connective Tissue Disease (MCTD) was first proposed by Sharp and his colleagues in 1972.1 MCTD has overlapping features between at least two autoimmune diseases, such as SLE, SSc, PM/DM and RA. Regulatory T cells (Treg cells) play a critical role in the maintenance of immune tolerance and the regulation of immune responses. Treg cell dysfunction contributes to the initiation of pathogenesis and the maintenance of high disease activity in RA and SLE.2 Recently, some studies have indicated that the proportion of Treg cells was different from healthy controls in SSc patients.3 Therefore, MCTD may be associated with Treg cells.
Objectives To explore the status of CD4+T cells in peripheral blood of patients with MCTD; to explore the effect of low dose interleukin -2 (IL-2) treatment on the balance of Treg cells and Th17 cells in patients with MCTD, and to observe the short-term curative effect.
Methods CD4+T cells in the peripheral blood of 58 MCTD patients and 33 healthy controls were analyzed by flow cytometry. All of 58 cases were treated with standard therapy, including corticosteroids, NSAIDs, immunosuppressants, or combination therapy. Among them, 26 cases of MCTD without using immunosuppressant (CYC, MTX, LEF, MMF), were as untreated group, another 32 cases were as treated group. Then we compared the difference of CD4+T cells between two groups. In 58 patients with MCTD, a total of 27 patients were treated with low-dose IL-2 (50WIU) on the basis of standard treatment for 5 days. The difference of CD4+T cells before and after treatment with IL-2 was compared.
Results The absolute count of CD4+CD25+FOXP3+Treg cells in peripheral blood of patients with MCTD was significantly lower than those in healthy controls. There was no significant difference in the absolute count of CD4+CD25+FOXP3+Treg cells in the peripheral blood between the treated group and the untreated group. The absolute count of CD4+CD25+FOXP3+Treg cells was significantly higher than those before treatment with IL-2.
Conclusions The absolute count of CD4+CD25+FOXP3+Treg cells in peripheral blood of patients with MCTD were significantly reduced, which may be the mechanism of immune imbalance in MCTD patients. The decrease of the absolute count of CD4+CD25+FOXP3+Treg cells in peripheral blood of patients with MCTD was not associated with the use of immunosuppressive agents. Low dose and short-term IL-2 treatment may increase the absolute count of CD4+CD25+FOXP3+Treg cells in the peripheral blood in patients with MCTD, so as to restore the immune balance in patients with MCTD.
Sharp GC, Irvin WS, Tan EM, et al. Mixed connective tissue disease – an apparently distinct rheumatic disease syndrome associated with a specifi c antibody to an extractable nuclear antigen (ENA). Am J Med 1972; 52: 148–159.
Vila J, Isaacs JD, Anderson AE. Regulatory T cells and autoimmunity. Curr Opin Hematol, 2009, 16(4):274–279.
Cordiali-Fei P, Mussi A, D'Agosto G, et al. Assessment of T regulatory cells and expanded profiling of autoantibodies may offer novel biomarkers for the clinical management of systemic sclerosis and undifferentiated connective tissue disease. Clin Dev Immunol, 2013, 2013:390563.
Acknowledgements Thanks to my supervisor, my colleagues and superiors.
Disclosure of Interest None declared