Distribution Of Circulating T Follicular Helper Cell Subsets Is Altered In Immunoglobulin A Vasculitis In Children

Objective:As a specialized subset of CD4~+T cells,circulating follicular helper T(cTfh)cells express the chemokine receptor CXCR5 and are supposed to be associated with autoimmune diseases.IgA Vasculitis(Ig AV)is the most common childhood vasculitis in most countries of the world,involving mainly small blood vessels.Previously,we demonstrated that patients with IgAV show abnormal proliferation of cluster of differentiation(CD)4~+C-X-C chemokine receptor type(CXCR)5~+follicular helper T(Tfh)cells.Here,we explored the status of Tfh cell subsets and plasma cytokine levels in patients with IgAV,aiming for further understanding the immunopathogenesis in IgAV.Methods:A total of 30 patients with active IgAV were recruited at the inpatient service of the Department of Pediatrics,the First Hospital of Jilin University from October 2015 to July 2016.Fifteen age and sex-matched healthy children were enrolled as healthy controls(HC)group.CD4~+CXCR5~+CD45RA~-,CD4~+CXCR5~+CD45RA~-CXCR3~+CCR6~-,CD4~+CXCR5~+CD45RA~-CXCR3~-CCR6~-,CD4~+CXCR5~+CD45RA~-CXCR3~-CCR6~+,andCD4~+CXCR5~+CD45RA~-CXCR3~+CCR6~+T cells in peripheral blood and plasma concentrations of interferon-γ,interleukin(IL)-4,and IL-17A were evaluated by flow cytometry and a flow cytometric bead array,respectively,in patients with Ig AV and healthy controls(HC).Statistical analyses were performed using SPSS v.19.0 software.Results:Circulating Tfh2 and Tfh17 cell fractions were larger and the Tfh2+Tfh17/Tfh1 ratio and plasma IL-4 and IL-17A levels were higher in patients with IgAV than those in the HC.Only cTfh1 cell counts were reduced in the abdominal subtype.however,the number of circulating Tfh1/17 cells did not differ between the two groups.The elevations in circulating Tfh2 and Tfh17cell counts and plasma IL-4 levels were abrogated by treatment.cTfh2 cell number was positively correlated with serum Ig A and plasma IL-4 levels,but negatively correlated with the serum C4 concentration,while cTfh17 cell number was positively correlated with the serum IgA level and cTfh2 cell counts.Conclusion:We found that different subset of cTfh cells may play distinct roles in Ig AV pathogenesis,especially in different types of IgAV.Abnormally high numbers of circulating Tfh2 and Tfh17 cells are linked to the occurrence and development of IgAV,but are not specific to the abdominal type.Only cTfh1cells play a critical role in abdominal-type IgAV.