Therapeutic effect of Bacillus Calmette-Guerin polysaccharide nucleic acid on mast cell at the transcriptional level.

Siyu Yan,Zhaoqian Liu,Runqiu Liu,Cong Peng,Yi Zhang,Wei Zhang,Manyun Mao,Xiang Chen,Jie Li

doi:10.7717/peerj.7404

Abstract

BackgroundChronic spontaneous urticaria (CSU) is a common and recurrent autoimmune-related disease with unclear pathogenesis. Dysfunction of immune cells, such as T cells, mast cells, and basophils, is involved. Bacillus Calmette–Guerin polysaccharide nucleic acid (BCG–PSN), an immunomodulator partially extracted from BCG, can be used in the combined treatment of CSU with an unknown mechanism.MethodsTo study the therapeutic effect and mechanism of BCG–PSN on CSU, we initially assessed the clinical efficacy in 110 enrolled CSU patients of 4-week antihistamine monotherapy vs. antihistamine plus BCG–PSN combined therapy. Subsequently, to explore the further mechanism of BCG-PSN, the mast cell line RBL-2H3 pretreated with BCG-PSN was used to evaluate the transcriptional expression profiles via lncRNA sequencing. Real time PCR was conducted to validate the candidate gene expression.ResultsWe found no significant difference in treatment efficacy between the BCG–PSN group (71.7%) and the monotherapy group (71.9%). However, the average time of complete relief in the BCG–PSN group was significantly shorter than that in the monotherapy group (36.77 ± 17.33 vs. 51.27 ± 16.80, p = 0.026). In vitro experiments showed that BCG-PSN inhibited β-hexosaminidase release rates in IgE-sensitized RBL-2H3 cells (p < 0.001). Sequencing data revealed the expression profiles of functional genes, including a significant decrease in Erb-B2 receptor tyrosine kinase 4, which can be regulated by the nuclear factor kappa B (NF-κB) pathway.DiscussionCSU is a chronic, recurrent disease with complex pathogenesis. Mast cells and basophils are the primary target cells of the disease. BCG–PSN decrease the β-HEX release rates and regulated IgE-mediated mast cell activation in RBL-2H3 cells by mediating immune-related gene expression including ERBB4. These findings suggest that BCG–PSN may mediate ERBB4 expression via the NF-κB pathway and may have value in the treatment of CSU.

Highlights

Chronic urticaria, a common and recurrent disease partly associated with autoimmunity (Altman & Chang, 2013; Confino-Cohen et al, 2012; Di Lorenzo et al, 2013; Zuberbier et al, 2018), is defined as having wheals, pruritus, and/or angioedema for more than six weeks
We aimed to investigate the therapeutic efficacy of BCG-PSN combined with antihistamines in Chronic spontaneous urticaria (CSU) patients and
53 were treated with Bacillus Calmette–Guerin polysaccharide nucleic acid (BCG–PSN) accompanied by antihistamine monotherapy, while 57 were treated with antihistamine monotherapy

Summary

Introduction

A common and recurrent disease partly associated with autoimmunity (Altman & Chang, 2013; Confino-Cohen et al, 2012; Di Lorenzo et al, 2013; Zuberbier et al, 2018), is defined as having wheals, pruritus, and/or angioedema for more than six weeks. Chronic spontaneous urticaria (CSU) is a common and recurrent autoimmune-related disease with unclear pathogenesis. Sequencing data revealed the expression profiles of functional genes, including a significant decrease in Erb-B2 receptor tyrosine kinase 4, which can be regulated by the nuclear factor kappa B (NF-κB) pathway. BCG–PSN decrease the βHEX release rates and regulated IgE-mediated mast cell activation in RBL-2H3 cells by mediating immune-related gene expression including ERBB4. These findings suggest that BCG–PSN may mediate ERBB4 expression via the NF-κB pathway and may have value in the treatment of CSU

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