The Expression And Significance Of Circulating Follicular Helper T Cells In Patients With Ankylosing Spondylitis

Objectives: The role of follicular helper T (TFH) cells remains unclear in thepathogenesis of ankylosing spondylitis (AS). This study was aimed atexamining the frequency of different subsets of circulating CXCR5+CD4+Tcells in patients with AS and following therapies.Methods: The percentages of peripheral blood inducible costimulator (ICOS)+,programmed death1(PD-1)+, and IL-21+CXCR5+CD4+T cells in26ASpatients and12healthy controls (HC) were examined by flow cytometry, andthe disease activity of individual patients was measured by the bath AS diseaseactivity index (BASDAI). The concentrations of serum IL-21, IgG, IgA, IgM,C-reactive protein (CRP) were examined and the values of erythrocytesedimentation rate (ESR) were measured. The potential association amongthese measures was analyzed.Results: In comparison with that in the HC, significantly increased percentagesof CXCR5+CD4+, CXCR5+CD4+PD-1+, and CXCR5+CD4+IL-21+, but notCXCR5+CD4+ICOS+and PD-1+ICOS+CXCR5+CD4+T cells, and elevatedconcentrations of serum IL-21were detected in the AS patients (p=0.001,p=0.012, p<0.001, p=0.233, p=0.216, p<0.001, respectively). Treatment withmeloxicam, thalidomide, and etanercept for one month significantly reduced the percentages of IL-21+CXCR5+CD4+T cells and the concentrations ofserum IL-21(p<0.001, p<0.001, respectively), accompanied by significantlyminimized disease activities in the drug-responders, but not in the drugnon-responders. Furthermore, the percentages of IL-21+CXCR5+CD4+T cellswere positively correlated with BASDAI in the patients (R=0.6, P=0.0012) andin those drug-responders one month after treatment (R=0.68, P=0.005), whilethe percentages of PD-1+CXCR5+CD4+T cells were negatively correlatedwith BASDAI (R=-0.58, P=0.0018).Conclusions: These data suggest that IL-21+CXCR5+CD4+T cells may beassociated with the development of AS and that the frequency ofIL-21+CXCR5+CD4+T cells may be a biomarker for the evaluation of diseaseactivity and drug responses in AS patients, particularly in drug-respondingpatients.