Association between Tfh and PGA in children with Henoch-Schönlein purpura.

Miao Meihua,Wang Qin,Zhu Yunfen,Shao Xunjun,Li Xiaozhong,Cui Yanyan

doi:10.1515/med-2021-0318

Miao Meihua, Wang Qin + Show 4 more

Open Access

https://doi.org/10.1515/med-2021-0318

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Abstract

ObjectiveThe aim of this study was to investigate the roles of follicular helper CD4+ T cells (Tfh) and serum anti-α-1,4-d-polygalacturonic acid (PGA) antibody in the pathogenesis of Henoch–Schönlein purpura (HSP).MethodsELISA was performed to determine serum PGA-IgA and PGA-IgG. Flow cytometry was utilized to determine the peripheral CD4+ CXCR5+ and CD4+ CXCR5+ ICOS+ Tfh cells. Real-time PCR was conducted to determine the expression of Bcl-6 gene. Then the change of Tfh cells was analyzed, together with the association with the anti-PGA antibody as well as the roles in the pathogenesis of HSP.ResultsCompared with the cases with acute respiratory infection and elective surgery, the proportion of CD4+ CXCR5+ and CD4+ CXCR5+ ICOS+ Tfh cells in the HSP group showed significant elevation (P < 0.001). A significant correlation was noticed between PGA-IgA and CD4+ CXCR5+ Tfh cells (r = 0.380 and P = 0.042) and CD4+ CXCR5+ ICOS+ Tfh cells (r = 0.906 and P < 0.001). The expression of Bcl-6 in the HSP group showed no statistical difference compared with that in the acute respiratory infection and the surgery control (P < 0.05).ConclusionIncreased activity of Tfh cells, which is closely related to mucosal immunity, may be a major contributor in the elevation of PGA-IgA, and Tfh cells and PGA-IgA are closely related to the occurrence of HSP.

Highlights

Henoch–Schönlein purpura (HSP), known as IgA vasculitis, is a common systemic disease in children
CD4-SSC was used for gating CD4+ cells, CD4-CXCR5 was used for gating CD4+ CXCR5+ Tfh from CD4+ cells and CXCR5-inducible T cell co-stimulator (ICOS) was used for gating CD4+ CXCR5+ ICOS+ Tfh cells from CD4+ CXCR5+ cells
The main feature of HSP is that immune complexes containing IgA-type antibodies are deposited on the affected small vessel wall, and IgA may be in the monomeric or multimeric form, while their multimeric forms may be associated with mucosal immune abnormalities [5,6,7,9]

Summary

Introduction

Henoch–Schönlein purpura (HSP), known as IgA vasculitis, is a common systemic disease in children. It is worth noting that the IgA-type antibodies associated with pathogenesis in the peripheral circulation of patients with nephritis-type HSP or IgA nephritis are mainly in the form of multimers [6,7], and the cells secreting the corresponding IgA-type antibodies are present in the bone marrow, tonsils and lymphatic follicles in the intestinal mucosa, along with the increase in number [8,9]. Tonsillectomy can significantly reduce serum IgA-type antibody levels [9] These findings suggest that mucosal B cells migrate to systemic immune sites such as the bone marrow, followed by abnormal homing, which continue to produce their “correct” mucosal IgA at new locations, resulting in increased levels of poly-IgA in serum [10,11]. Mucosal infection and its immune response are considered to be potential mechanisms for elevated serum IgA in HSP [12]

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