Distinct phenotypic subpopulations of circulating CD4+CXCR5+ follicular helper T cells in children with active IgA vasculitis.

Deying Liu,Congcong Liu,Jinghua Wang,Yanfang Jiang,Jinxiang Liu,Sirui Yang

doi:10.1186/s12865-016-0176-6

Abstract

BackgroundCirculating follicular helper T (Tfh) cells are a heterogeneous population of CD4+ helper T cells that promotes pathogenic immune responses in autoimmune diseases. In this study, we examined the status of different subpopulations of Tfh cells in peripheral circulation and their associations with various clinical characteristics of IgA vasculitis (IgAV).MethodsAccording to the phenotypic expressions of different molecules, focus was given on six subpopulations of Tfh cells: CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+ICOS+PD-1+, CD4+CXCR5+ICOShighPD-1high, CD4+CXCR5+ICOS−PD-1+, and CXCR5+CD45RA−IL-21+. The frequencies of these six subpopulations and the circulating level of Tfh-related cytokine interleukin 21 (IL-21) were measured from 27 patients with IgAV and 15 healthy controls (HC) by flow cytometry and flow cytometric bead array, respectively.ResultsSignificantly higher frequencies of CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+ICOS+PD-1+, CD4+CXCR5+ICOShighPD-1high and CXCR5+CD45RA−IL-21+ Tfh cells, as well as higher levels of plasma IL-21, were detected in IgAV patients compared to HC. The level of each Tfh subpopulation varied by the presenting symptoms of IgAV, but did not differ between patients treated or not treated with glucocorticoids. When the disease entered the remission stage following treatment, circulating levels of CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+ICOS+PD-1+, CD4+CXCR5+ICOShighPD-1high and CXCR5+CD45RA−IL-21+ Tfh cells, as well as plasma IL-21 levels were reduced. Among the six subpopulations of Tfh cells, both CD4+CXCR5+ICOS+ and CXCR5+CD45RA−IL-21+ significantly and positively correlated with serum IgA and plasma IL-21 levels, but only CXCR5+CD45RA−IL-21+ significantly and negatively correlated with the serum C4 level.ConclusionsTfh cells may differentially contribute to the development of IgAV or predict disease progression. These findings provide novel insights in the pathogenesis of IgAV and may benefit treatment development targeting organ-specific presenting symptoms of IgAV.

Highlights

Circulating follicular helper T (Tfh) cells are a heterogeneous population of CD4+ helper T cells that promotes pathogenic immune responses in autoimmune diseases
In order to address these questions, in this study, we focused on six phenotypic subpopulations of circulating Tfh cells as defined by the expressions of distinct molecules, examined their associations with IgA vasculitis (IgAV), the different dominant symptoms presented in IgAV, and explored the correlations between these Tfh subpopulations and key IgAV clinical parameters
The white blood cell (WBC) count (P < 0.0001), platelet (P = 0.0045), serum IgA (P = 0.0097), IgE (P = 0.0371) and complement C4 (P = 0.0476) levels were significantly higher in IgAV patients than in healthy controls (HC) (Table 1)

Summary

Introduction

Circulating follicular helper T (Tfh) cells are a heterogeneous population of CD4+ helper T cells that promotes pathogenic immune responses in autoimmune diseases. We examined the status of different subpopulations of Tfh cells in peripheral circulation and their associations with various clinical characteristics of IgA vasculitis (IgAV). Immunoglobulin A vasculitis (IgAV), known as Henoch-Schönlein purpura, is an autoimmune disease caused by the deposition of IgA-dominant immune complexes in small vessels [1, 2]. Complications resulting from blood vessel lesions in different organ systems could sometimes be severe, of which, renal involvement is the most serious complication and the principle cause of mortality in IgAV patients [6,7,8]

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