Background DMARDs are the most important medicine in treatment of autoimmune disease. However, excessive using DMARDs lead to decrease immune-function, which increasing opportunistic infection, such as EBV, CMV viremia. Recent study show the imbalance between T help cell 17 (Th17) and regulatory T cell (Treg cell) is a pivotal cause of autoimmune disease and correction of this imbalance to be a potential therapy. So whether low dose IL-2 restores the balance of Th17/Treg and improve immune function?
Objectives To investigate the effect of low-dose IL-2 on Treg and effector lymphocyte subsets in patients with connective tissue disease (CTD) combined EBV or CMV viremia.
Methods Clinical records of 70 CTD patients combined EBV or CMV viremia, hospitalized from May 2012 to January 2017 in the second Hospital of ShanXi medical university (Group infection), were analyzed. The group includes 21 patients who received rhIL-2 after infected CMV or EBV, and 12 continue receiving DMARDs. As control, we selected 70 health persons (Group health) whose age matched with group infection, 70 naïve CTD patients with no treatment (Group treatment-naïve), and 70 CTD without viremia patients having glucocorticoid and DMARDS medical history (Group Treatment-DMARDS). The two groups' underlying diseases are matched with the Group infection. The absolute numbers and proportions of peripheral lymphocytes (T cells, B cells, NK cells, the total number of the three cells, CD4+ T cells, CD8+ T cells), and CD4+ T cell subsets (Th1, Th2, Th17, Treg cells and Th1/Th2, Th17/Treg) were examined by flow cytometry.
Results 1. The absolute count of Treg cells in the Group treatment-naïve was significantly low and Th17/Treg was notable increase compared with the Group health (P<0.05). The peripheral lymphocytes and Treg cells are notable low (P<0.05) and Th17/Treg was significantly increase (P<0.05) in the Group treatment-DMARDs compared with the Group treatment-naïve.
2. The peripheral lymphocytes, CD4+T cells subsets except Treg cells and Th1/Th2, Th17/Treg are significantly decrease in the Group infection compared with the Group treatment-DMARDs (P<0.05). While the absolute count of Treg cell was no different between the two groups.
3. After the course of rhIL-2 treatment, there were significantly increase of the peripheral lymphocytes and CD4+T cells subsets (P<0.01). Th17/Treg was significantly low after treatment. Compared with the patients who continue receiving DMARDs, all lymphocytes subsets had a rising trend in patients receiving rhIL-2 treatment.
Conclusions The decrease of Treg cell number and imbalance of Th17/Treg may contribute to the pathogenesis of CTD. Excessive using glucocorticoid and DMARDs may augment this imbalance. On the other hand, these medicines decrease immune function, which leads to EBV and CMV viremia. Over the treatment of rhIL-2, immune function was improved and there was a more significant increase in the absolute count of Treg cells than Th17, and a consequently restore the balance of Th17/Treg.
Miyara M, Ito Y, Sakaguchi S. TREG-cell therapies for autoimmune rheumatic diseases. Nature reviews Rheumatology 2014;10:543–51.
Klatzmann D, Abbas AK. The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases. Nature reviews Immunology 2015;15:283–94.
Disclosure of Interest None declared