Pathogenic role of circulating CD4+CXCR5+ cell subpopulations in patients with chronic spontaneous urticarial

Am J Transl Res. 2020 Aug 15;12(8):4434-4444. eCollection 2020.

Abstract

Accumulating evidence demonstrated that circulating CD4+CXCR5+, follicular helper T (Tfh) and follicular regulatory T (Tfr) cells maintain immune homeostasis and humoral immune response and were involved in the pathogenesis of certain autoimmune/inflammatory diseases. The current study was aimed to investigate the correlation between frequencies of CD4+CXCR5+, Tfh and Tfr cells, Tfh/Tfr and the disease activity in chronic spontaneous urticaria (CSU). Frequencies of CD4+CXCR5+, Tfh and Tfh/Tfr, but not Tfr, in peripheral blood mononuclear cells (PBMCs) were elevated in patients with CSU as compared with healthy controls. No difference was observed in the frequency of these cells between different subgroups of patients based on autologous serum skin testing (ASST), skin prick testing (SPT) and the level of total IgE. The expression of CXCR5 in PBMCs was higher in CSU than in controls, both at mRNA and protein levels. Higher levels of plasma IL-4, IL-6 and total IgE were observed in CSU, with positive correlation between IL-4/IL-6 and total IgE. The IL-21 level was lower and negatively correlated with total IgE. Using receiver operating characteristic (ROC) curve, we found positive correlation between the urticaria activity score (UAS) and CD4+CXCR5+, Tfh, Tfh/Tfr and total IgE, respectively, with area under the curves (AUCs) all greater than 0.7 (P < 0.05). These results indicated that frequencies of circulating CD4+CXCR5+ cells, Tfh cells and Tfh/Tfr were abnormal and correlated positively with disease severity, suggesting the possible involvement of these cells in the immunopathogenesis of CSU.

Keywords: CD4+CXCR5+ cell; Chronic spontaneous urticaria; follicular helper T cell; follicular regulatory T cell; urticaria activity score.