Impaired function of regulatory T-cells (Treg) leads to a failure in immune tolerance and triggers autoimmunity. We analyzed whether the deficiency in Treg in systemic lupus erythematosus (SLE) is accompanied by an increase in effector T-cell responses. We studied the frequencies of IL-17A (Th17) and IFNg (Th1) producing CD4 + T-cells by flow cytometric detection of intracellular cytokines in PMA/ionomycin stimulated blood lymphocytes from seven patients with active SLE, eight with SLE in remission, and 11 healthy controls. Circulating Treg were evaluated as CD4 + CD25 + lymphocytes expressing FoxP3. There was no difference in the percentage of Treg cells between the groups, but their absolute counts were decreased in active SLE (5 [1-7] cells/μL) compared to inactive SLE (11 [6][7][8][9][10][11][12][13][14][15]; p = 0.05) and healthy controls (16 [10-20]; p < 0.01). Both the frequency and numbers of Th1 cells were decreased in SLE compared to controls. No difference was observed in the number of Th17 cells, which resulted in a decreased Th1/Th17 ratio. In parallel, a higher Treg/Th17 ratio in healthy controls (2.2 [1.8-3.6]) compared to active SLE (1.1 [1.0-2.1]; p < 0.05) was observed. There was a correlation between the number of Treg cells and disease activity status (SLEDAI, r = -0.59). SLE patients in the active phase of the disease are characterized by a deficiency in Treg cells and decreased Treg/Th17 ratio. This suggests that the imbalance between major T-cells subsets might be responsible for an increased proinflammatory response in the exacerbation

Background Defective function of regulatory T cells (Treg) leads to the impairment of immune tolerance implicated in the pathogenesis of autoimmune inflammation in systemic lupus erythematosus (SLE). Methods To investigate the role of Treg in SLE we studied peripheral blood Treg and CD4+ effector T-helper cells (Th1, Th17), expression of their signature cytokines by in vitro activated lymphocytes (real-time PCR), and levels of TGF-β1, IL-10 and IL-17A (ELISA) in sera from patients with active–SLE (n=13), inactive-SLE (n=13) and matched healthy subjects (n=13). Results There was a significant decrease in CD4+ lymphocyte count in active SLE, with no evident difference in the percentage of CD25+FoxP3+ Treg cells as compared to other groups. Treg absolute counts decreased significantly in active-SLE (∼2-fold as compared to controls) and weakly correlated with markers of disease activity (C4, r=0.44). Only Th1 (IFN-γ producing) cells, but not Th17 (IL-17A producing) cells decreased in active disease, resulting in lower Th1/Th17 ratio. This was confirmed by a lower expression of IFN-γ mRNA (but not IL-17A) in peripheral blood lymphocytes from patients with active-SLE. All patients with SLE were characterized by lower Treg/Th17 ratio (median 1.4 vs. 2.4 in controls, p<0.001). Additionally, in patients with SLE exacerbation we observed higher levels of serum IL-17A (p<0.05 vs. controls) together with a decrease in concentration of immunoregulatory TGF-β1 (p<0.05) and elevated IL-10 (p<0.01) as compared to other groups. However, only IL-10 correlated with SLEDAI score (r=0.57) and negatively with levels of C4 (r=-0.59), probably as a compensatory mechanism related to immune activation. Conclusions Our data suggest, that SLE associated lymphopenia affects primarily Treg and Th1, but not Th17 fraction, resulting in imbalance between regulatory and effector CD4+ subsets. This may lead to relative deficiency in suppressive function of Treg (as evidenced by decrease in TGF-β1), and consequently to the increased proinflammatory response during active phase of the disease. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3602