IFN-γ, TNF-α, IL-10, IL-17 and IL-22 secretion capacities and activation profile of T cells in psoriatic arthritis patients under disease-modifying antirheumatic drug therapy.

Abstract

Introduction: While biologic disease-modifying antirheumatic drugs (bDMARDs) have transformed management, achieving complete remission remains a challenge due to complex immune networks in Psoriatic arthritis (PsA). This study aimed to characterize the functional modulation of circulating T-helper (Th) and cytotoxic T (Tc) cells in PsA patients following conventional synthetic (csDMARD) and biologic therapy.

Methods: Peripheral blood mononuclear cells were collected from bDMARD-naïve PsA patients at baseline and six months after initiating csDMARD (primarily methotrexate, n=8) or bDMARD (primarily certolizumab, n=11) therapy. Using an optimized flow cytometry-based assay, we evaluated the secretion capacities of TNF-α, IFN-γ, IL-17, IL-22, and IL-10, alongside activation markers (CD40L, ICOS, CD38) in CD4⁺ Th and CD8⁺ Tc cells. Results were associated with clinical disease activity indices (DAPSA, BASDAI, PsAID-12, LEI).

Results: Both therapies significantly improved clinical scores yet failed to achieve immunological quiescence. A central finding was a significant increase in the percentage of TNF-secreting Th and Tc cells post-therapy, which may reflect a compensatory change in T-cell cytokine secretion following treatment. In the bDMARD cohort, Tc cells exhibited a significant expansion of subsets secreting IFN-γ, IL-17, and IL-10, suggesting a possible shift toward Type 1/Type 17-related cytokine responses. Baseline IL-17 and IL-10 levels correlated positively with high disease activity (BASDAI/PsAID-12), while post-treatment IL-17 and IL-22 secretory potential was specifically associated with persistent enthesitis (LEI scores).

Discussion: Despite clinical efficacy, DMARD therapy was associated with persistent alterations in T-cell cytokine profiles, including IFN-γ- and IL-17-producing T-cell populations, particularly within the CD8+ compartment. These findings suggest that peripheral immune profiling may provide additional insights into the immunological effects of therapy and could contribute to future personalized approaches for monitoring immune responses in patients with PsA.