Distribution of distinct subsets of circulating T follicular helper cells in Kawasaki disease

Meng Xu,Sirui Yang,Huanfa Yi,Yanfang Jiang,Deying Liu,Shaofeng Wang,Jinghua Wang

doi:10.1186/s12887-019-1412-z

Abstract

BackgroundKawasaki disease (KD) is an acute febrile vasculitis that primarily affects children. Previous studies have shown that both innate and adapt immune systems are involved in the immunopathogenesis of KD. The following study analyzes the distribution of the subsets of Circulating T follicular helper cells (cTfh cells) in KD patients with and without coronary artery lesions (CALs).MethodsTwenty KD patients and fifteen healthy sex- and age- matched children were enrolled. Patients were divided into two groups depending on CALs. Blood samples were collected respectively before and after intravenous immunoglobulin (IVIG) administration. Circulating Tfh cells were categorized into three subsets by flow cytometry including cTfh1 (CXCR3 + CCR6-), cTfh2 (CXCR3-CCX6-) and cTfh17 (CXCR3-CCR6+) cells in circulating CD3 + CD4 + CXCR5 + CD45RA- T cells. Cytometric bead arrays were used to analyze the level of IFN-γ, IL-4 and IL-17A.ResultsWe found that frequency of cTfh2 cells was significantly elevated in KD patients before IVIG administration with low expression of cTfh1 cells, where the ratio of cTfh2 + cTfh17/cTfh1 significantly increased. Levels of IFN-γ, IL-4 and IL-17A in KD were significantly higher compared to controls. Further analysis showed that cTfh1 cells were negatively correlated with serum CRP, whereas cTfh2 cells were positively correlated with serum CRP and ESR. Comparison of different groups showed that frequency of cTfh1 cells in CALs+ group were significantly lower compared to CALs- group. In contrast, cTfh2 cells in CALs+ group significantly increased. After IVIG administration, frequency of cTfh2 cells and the ratio significantly decreased while the frequency of cTfh1 cells significantly increased. Meanwhile, all levels of cytokines decreased.ConclusionsOur data demonstrated that cTfh1 and cTfh2 cells participate in the pathogenesis of KD, and that the two subsets might be associated with CALs.

Highlights

Kawasaki disease (KD) is an acute febrile vasculitis that primarily affects children
We focus on the subsets of circulating Tfh cells in KD patients including those with and without coronary artery lesions, where we analyze their association with clinical parameters
There were no significant differences in lymphocyte counts or serum immunoglobulin concentrations including IgG, IgA and IgM, neither between KD patients and controls or between coronary artery lesions (CALs)+ and CALs

Summary

Introduction

Kawasaki disease (KD) is an acute febrile vasculitis that primarily affects children. Previous studies have shown that both innate and adapt immune systems are involved in the immunopathogenesis of KD. The following study analyzes the distribution of the subsets of Circulating T follicular helper cells (cTfh cells) in KD patients with and without coronary artery lesions (CALs). Studies related to immune response have suggested that both innate and adaptive immune systems are involved, leading to impaired immune homeostasis [2, 3]. Given circulating Tfh (cTfh) cells share the immunophenotype and functional nature of GC Tfh cells, cTfh cells can be categorized into distinct subsets by differential expression of biomarker such as CXCR3 and CCR6. Current understanding of aberrant cTfh response has shown that imbalance of cTfh-cell subsets, which represents over-expression in cTfh or cTfh cells and under-expression in cTfh cells, is related to multiple diseases. The association between these three subsets and Kawasaki disease remains to be investigated

Methods

Results

Discussion

Conclusion