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AB0029 Imbalance between Immunoregulatory and Effector TH17 Pathway in Active Sle
  1. B. Jakiela,
  2. W. Kleczynska,
  3. J. Kosalka,
  4. H. Plutecka,
  5. M. Sanak,
  6. J. Musial
  1. Dpt of Medicine, Jagiellonian University Medical College, Krakow, Poland

Abstract

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

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