title: Higher frequency of peripheral blood interleukin 21 positive follicular helper T cells in patients with ankylosing spondylitis.
abstract: OBJECTIVE
  The role of follicular Th (TFH) cells remains unclear in the pathogenesis of ankylosing spondylitis (AS). Our study examined the frequency of different subsets of circulating CXCR5+CD4+ T cells in patients with AS before and after receiving therapy.
  
  
  METHODS
  Percentages of peripheral blood inducible costimulator (ICOS)+, programmed death 1 (PD-1)+, and interleukin 21 (IL-21)+ CXCR5+CD4+ T cells in 26 patients with AS and 12 healthy controls (HC) were examined by flow cytometry, and the disease activity of individual patients was measured by Bath AS Disease Activity Index (BASDAI). The concentrations of serum IL-21, IgG, IgA, IgM, and C-reactive protein (CRP) were examined and the values of erythrocyte sedimentation rate (ESR) were measured. The potential association among these measures was analyzed.
  
  
  RESULTS
  In comparison with that in HC, significantly increased percentages of CXCR5+CD4+, CXCR5+CD4+PD-1+, and CXCR5+CD4+IL-21+, but not CXCR5+CD4+ICOS+ and PD-1+ICOS+CXCR5+CD4+ T cells, and elevated concentrations of serum IL-21 were detected in patients with AS (p = 0.001, p = 0.012, p < 0.001, p = 0.233, p = 0.216, p < 0.001, respectively). Treatment with meloxicam, thalidomide, and etanercept for 1 month significantly reduced percentages of IL-21+CXCR5+CD4+ T cells and concentrations of serum IL-21 (p < 0.001, p < 0.001, respectively), accompanied by significantly minimized disease activity in drug responders, but not in the drug nonresponders. Further, percentages of IL-21+CXCR5+CD4+ T cells were positively correlated with BASDAI in patients (r = 0.6, p = 0.0012) and in the drug-responders 1 month after treatment (r = 0.68, p = 0.005), while the percentages of PD-1+CXCR5+CD4+ T cells were negatively correlated with BASDAI (r = -0.58, p = 0.0018).
  
  
  CONCLUSIONS
  These data suggest that IL-21+CXCR5+CD4+ T cells may be associated with development of AS and that the frequency of IL-21+CXCR5+CD4+ T cells may be a biomarker for evaluation of disease activity and drug responses in patients with AS, particularly in drug-responding patients.
authors.affiliation: From the Key Laboratory of Zoonosis Research, Ministry of Education, the Second Part of First Hospital, Jilin University, Changchun, 130032, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.forename: Hai-Yu
authors.initials: HY
authors.lastname: Zhang
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Ding
authors.initials: D
authors.lastname: Zhao
authors.forename: Yu-Xing
authors.initials: YX
authors.lastname: Shan
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000097:blood* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism; D054380:Receptors, CXCR5 / Q000276:immunology / Q000378:metabolism; D013167:Spondylitis, Ankylosing / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: C095085:CXCR5 protein, human; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D007378:Interleukins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D054380:Receptors, CXCR5; D000098546:Interleukin-21
keywords: ANKYLOSING SPONDYLITIS; DISEASE ACTIVITY; FOLLICULAR HELPER T CELLS; INTERLEUKIN 21; THERAPEUTIC RESPONSE