Abstract
Systemic immune defects might reflect severely dysregulated control of chronic inflammation related to disease progression. Th17/Treg cell imbalance has been demonstrated to be involved in rheumatoid arthritis (RA) pathogenesis. Despite controversial results, a growing anti-inflammatory role in this process has been recently attributed to Th1 responses. The aim of the study was to estimate the extent of Th1/Th17/Treg imbalance in peripheral blood (PB) of patients with short- and long-term RA in relation to cytokine milieu and its reversal after therapy with methotrexate and/or TNF inhibitors, respectively. Patients with different duration of RA (median 6 vs. 120 months) in the active phase of RA were enrolled in this study. We performed flow cytometric analysis of PB Th1, Th17, and Treg populations together with estimation of serum cytokine concentrations using cytometric bead array. Disease activity was calculated on the basis of clinical and biochemical indices of inflammation (DAS28, ESR, CRP). All parameters were measured and correlated with each other before and after 6 months therapy. Elevated levels of circulating Th17 cells and IL-6 were found in all active patients, of which Th17 cells were down-regulated by the treatment. Significantly reduced Th1 and functional CTLA-4+ Treg cell frequencies as well as Th1 cytokines observed only in progressive RA seemed to be irreversible. Although therapy induced clinical improvement in almost all patients, those with advanced RA remained with signs of inflammation. Our report demonstrates that both the extent of systemic immune abnormalities and their restoration are dependent on duration of the active RA.
Highlights
Rheumatoid arthritis (RA) is one of the most common systemic autoimmune diseases
Our present work strongly demonstrates that RA patients present an imbalance in CD4 T cell subsets’ distribution in peripheral blood (PB), more pronounced in those with the most advanced disease, suggesting the impact of disease progression on subsequent changes
Considering CD4 T cell subpopulations, a common disorder found in all RA patients irrespective of the disease duration was expansion of Th17 cells in circulation
Summary
Rheumatoid arthritis (RA) is one of the most common systemic autoimmune diseases. It is characterized by chronic inflammation in the synovium, resulting in progressive destruction of joints and cartilage. The persistent nature of arthritis strongly suggests immune dysfunctions associated with predominance of the pro-inflammatory responses. It seems that both local and systemic immune abnormalities may be involved in the disease development and evolution. Helper T cells (Th cells) play a major role in initiation and maintenance of the chronic inflammation in RA [1]. According to the cytokine microenvironment, CD4 T cells differentiate toward various pro- and anti-inflammatory subpopulations, including Th1, Th2, Th17, and T regulatory (Treg) cells, playing important roles in the pathogenesis of RA [2]
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