Residual activated Th17 cells during inactive disease or low disease activity are associated with subsequent disease worsening in radiographic axial spondyloarthritis: a pilot study.

OBJECTIVE: To investigate whether residual activated T helper 17 (Th17) cells during inactive disease or low disease activity (LDA) in radiographic axial spondyloarthritis (r-axSpA) are associated with subsequent disease instability. METHODS: Patients with r-axSpA in inactive disease or LDA (Axial Spondyloarthritis Disease Activity Score [ASDAS]<2.1) were included. Peripheral blood mononuclear cells obtained at baseline were analyzed using multicolor flow cytometry. Activated Th17 cells were defined as CD3+CD4+CXCR3-CCR6+CD38+HLA-DR+ cells. Patients were categorized into activated Th17-high and activated Th17-low groups according to the receiver operating characteristics-derived cut-off value of activated Th17 cells among CD4+ T cells. ASDAS was assessed at baseline, 3 months, and 6 months. ASDAS trajectories were analyzed using linear mixed-effects models, and the proportion of patients experiencing loss of LDA (ASDAS≥2.1) was compared between groups. RESULTS: Twenty-one patients with r-axSpA were included (activated Th17-high, n=9; activated Th17-low, n=12). The activated Th17-high group showed a significantly worse ASDAS trajectory during follow-up than the activated Th17-low group (P for interaction<0.05). Loss of LDA occurred in 4 patients (44.4%) in the activated Th17-high group and in none in the activated Th17-low group (P<0.05). Baseline disease activity status (inactive disease [ASDAS<1.3] vs. LDA [1.3≤ASDAS<2.1]) was not associated with differences in ASDAS trajectories (P for interaction=non-significant) or loss of LDA (P=non-significant). CONCLUSION: Residual activated Th17 cells during inactive disease or LDA are associated with subsequent disease worsening in r-axSpA. Cellular immune profiling may help identify patients at risk of disease instability despite apparent clinical control.