Impaired T Cell-dependent Humoral Immune Response Associated with Juvenile-onset Recurrent Respiratory Papillomatosis Progression.

Xunyao Wu,Jie Zhang,Jingang Gui,Jun Wang,Shengcai Wang,Yang Xiao,Lina Bai,Xi Chen,Guoliang Wang,Jing Zhao,Guixiang Wang,Hua Wang,Xin Ni,Jun Tai

doi:10.1038/srep36378

Abstract

Whether humoral immunity plays a role in HPV type 6 or 11 virus-mediated Juvenile-onset Recurrent Respiratory Papillomatosis (JORRP) remains unknown. In the present study, serum total IgG level in 44 JORRP patients was significantly decreased compared with that in 40 healthy controls. Moreover, expanded CD3−CD19+ B cells with down-regulation of CD23, CD40, HLA-DR and up-regulation of CD86 expression were found in the peripheral blood of JORRP patients. Flow cytometry analysis of B-cell compartment showed that the frequency of both CD19+CD27hi plasma cells and CD19+CD27+ memory B cells were decreased in JORRP patients. Importantly, although the proportion of circulating CXCR5+PD1hi Tfh cells was not changed, the function of Tfh cells were greatly impaired with reduced ability of IL-21 secretion to promote B cell maturation. Association analysis by the Kaplan-Meier method revealed that IL-21 secreting Tfh cell was positively correlated to the CD27+ B cell subset frequency, the serum IgG level and the frequency of recurrence in JORRP patients, but negatively correlated to the percentage of IgD+CD27− B cell. We concluded that a reduced IL-21 secretion by Tfh cells may limit B cell maturation and antibody production in JORRP patients and Tfh cell-derived IL-21 might be associated with JORRP outcome in clinic.

Highlights

While persistent Human Papillomatosis Virus (HPV) type 6 or 11 virus infection is often associated with Juvenile-onset Recurrent Respiratory Papillomatosis (JORRP) development[5], emerging evidences showed that immune responses against HPV type 6 or 11 virus infection are the determinants of JORRP outcome[6]
While dysfunction of cellular immune responses against HPV type 6 or 11 virus infection are described in various studies[6,7], whether humoral immunity involves in the progression of JORRP remains unknown
We examined B-cell related humoral response and observed a significant expanded immature B cells in patients diagnosed with JORRP compared to healthy controls

Summary

Introduction

While persistent Human Papillomatosis Virus (HPV) type 6 or 11 virus infection is often associated with JORRP development[5], emerging evidences showed that immune responses against HPV type 6 or 11 virus infection are the determinants of JORRP outcome[6]. It has been suggested that impaired cellular immune response in patients with JORRP support sustained HPV-6/11 infection and prevent HPV virus from clearance. We observed a reduction in plasma and memory B cells that was associated with decreased serum IgG production in JORRP patients. An impaired secretion of IL-21 by Tfh cells, possibly leading to the immaturity of B-cell development, was correlated to a reduced serum IgG level and an increased recurrent frequency in JORRP patient. These results suggest that Tfh-cell-mediated humoral immunity play an important role in the outcome of JORRP in clinic

Methods

Results

Conclusion