T-Helper Cell Cytokine Expression Profiling in Rheumatoid Arthritis Patients by Flow Cytometric Bead Array Analysis

Background: Rheumatoid arthritis (RA) is the most common chronic autoimmune disease affecting multiple joints. A chronic imbalance in cytokine production by T-helper (Th) cells is likely a key factor in RA development. Our objective was to profile the serum cytokine expression from three key Th cell types (Th1, Th2, and Th17) in RA patients in order to correlate the resulting cytokine expression profiles with RA activity. Material and Methods: From a population of RA patients (n = 71) and healthy controls (n = 18), the serum concentrations of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and TNF-α) were analyzed by flow cytometric bead array (CBA). Results: The serum concentrations of all seven cytokines were significantly higher in RA patients than in healthy controls. Interestingly, the serum concentration profiles varied with the 28-joint Disease Activity Score (DAS28), a measure of RA activity derived from joint indices (tender joints and swollen joints count) and the erythrocyte sedimentation rate. In the high RA activity group (DAS28 > 5.1), all seven cytokines were significantly elevated. In the moderate RA activity group (DAS28 between 3.2 and 5.1), only IL-2, IL-6, IL-10, and IL-17A were significantly increased. In the low RA activity group (DAS28 ≤ 3.2), only IL-2, IL-4, and TNF-α were significantly elevated. Conclusions: The Th cell-derived cytokine expression profile significantly changes across varying levels of RA activity. Th1/Th17 cell-derived TNF-α and Th2 cell-derived IL-4 appear to play more important roles in the early stages of RA, while all seven cytokines derived from Th1, Th2, and Th17 cells (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and TNF-α) are overtly involved in the advanced stages of RA