Patients with the most advanced rheumatoid arthrit

Authors: Agata Kosmaczewska Jerzy Swierkot Lidia Ciszak Aleksandra Szteblich Agnieszka Chrobak Lidia Karabon Anna Partyka Jacek Szechinski Piotr Wiland Irena Frydecka

Publish Date: 2013/11/13

Volume: 34, Issue: 2, Pages: 243-253

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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 antiinflammatory 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 longterm 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 IL6 were found in all active patients of which Th17 cells were downregulated by the treatment Significantly reduced Th1 and functional CTLA4+ 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 RARheumatoid 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 proinflammatory 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 antiinflammatory subpopulations including Th1 Th2 Th17 and T regulatory Treg cells playing important roles in the pathogenesis of RA 2It has been shown that active RA results from an imbalance in the distribution of proinflammatory Th17 and antiinflammatory Treg cells which emphasizes the crucial roles of these cells in controlling RA 3 Th1/Th17/Treg subsets can act as important participants of the complex network of interactions that manage the development and progression of RA and what is more important they can exhibit this action at different stages of the disease with different intensities Recent data have suggested interferongamma IFNγ and/or interleukin2 IL2 to be protective rather than proinflammatory cytokines that could be involved in the downregulation of RArelated chronic inflammation 4 5 In light of the controversial results the exact impact of Th1 cell responses on Th17/Treg cell systemic distribution in RA remains uncertain 6Therefore we performed a comparative analysis of Th1/Th17/Treg cell distribution in relation to cytokine milieu in peripheral blood PB of patients divided into two groups with regard to RA duration early and advanced stages of RA Then we evaluated modifications of studied parameters after 6 months of therapy with methotrexate MTX and/or tumor necrosis factor inhibitors iTNF We also correlated the results with clinical and laboratory markers of inflammation DAS28 CRP ESR at each time point tested All results were compared to those obtained in healthy controls

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