白细胞介素-1β 和白细胞介素-6 在普通变异性免疫缺陷中的作用及其与 B 细胞亚型的关系和对肺炎球菌疫苗 23 的反应。

Interleukin-1β and interleukin-6 in Common Variable Immunodeficiency and their association with subtypes of B cells and response to the Pneumovax-23 vaccine.

机构信息

Research Center for Immunodeﬁciencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran, Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Research Center for Immunodeﬁciencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran, Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran.

出版信息

Eur Cytokine Netw. 2019 Dec 1;30(4):123-129. doi: 10.1684/ecn.2019.0435.

DOI:10.1684/ecn.2019.0435

PMID:32096473

Abstract

INTRODUCTION

Common Variable Immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiencies. Current research data show altered B cells, TLRs, and cytokine profile in CVID patients. The aim of this study was to determine levels of IL-1β and IL-6 in CVID patients in response to TLRs stimulation and the association of these cytokines with subtypes of B cells and response to Pneumovax-23 vaccination.

METHOD

Peripheral blood mononuclear cells of CIVD patients were stimulated with and without TLR2 and TLR4 agonist and specific inhibitors including lipopolysaccharide (LPS), lipoteichoic (LTA), and OxPAPC. The levels of IL-1β and IL-6 were assessed by ELISA in different treatment groups. Finally, association of cytokines levels was assessed among different subtypes of B cells and types of response to Pneumovax-23 vaccine.

RESULTS

Secretion of IL-6 and IL-1β was significantly diminished in CVID patients (p = 0.015 and p = 0.019), but ligand engagement of TLR2 and TLR4 leads to significant increase in IL-6 and IL-1β production. IL-6 was significantly lower in Pneumovax-23 hypo responder patients (p = 0.05) and significant correlations between the concentration of IL-6 and the number of switched memory and CD21 expressing B cells were found.

CONCLUSION

Secretion of IL-6 and IL-1β is abolished in CVID patients. However, TLR2 and TLR4 are hyper responsive to stimulation with their cognate ligands resulting in the secretion of higher levels of proinflammatory cytokines. This characteristic of CVID TLRs leads to an improvement of cytokine secretion compared to baseline levels. Also, our novel findings about the association concentrations of serum IL-6 and the frequency of with switched memory and CD21 expressing B cells as well as the poor response to Pneumovax-23 should be substantiated by the use of a higher sample size in future studies.

摘要

简介

常见变异性免疫缺陷（CVID）是原发性免疫缺陷症中最常见的有症状形式。目前的研究数据显示，CVID 患者的 B 细胞、TLR 和细胞因子谱发生改变。本研究旨在确定 CVID 患者在 TLR 刺激下的 IL-1β 和 IL-6 水平，以及这些细胞因子与 B 细胞亚类和对 Pneumovax-23 疫苗的反应之间的关系。

方法

用 TLR2 和 TLR4 激动剂和特异性抑制剂（包括脂多糖[LPS]、脂磷壁酸[LTA]和 OxPAPC）刺激 CIVD 患者的外周血单核细胞。用 ELISA 在不同处理组中检测 IL-1β 和 IL-6 的水平。最后，评估细胞因子水平与不同 B 细胞亚类和 Pneumovax-23 疫苗反应类型之间的关系。

结果

CVID 患者的 IL-6 和 IL-1β 分泌明显减少（p=0.015 和 p=0.019），但 TLR2 和 TLR4 的配体结合导致 IL-6 和 IL-1β 产生显著增加。Pneumovax-23 低反应者的 IL-6 水平明显较低（p=0.05），并且发现 IL-6 浓度与转换记忆和 CD21 表达 B 细胞的数量之间存在显著相关性。

结论

CVID 患者的 IL-6 和 IL-1β 分泌被阻断。然而，TLR2 和 TLR4 对其配体的刺激反应过度，导致促炎细胞因子的分泌水平升高。CVID TLR 的这种特征导致细胞因子分泌水平高于基线水平。此外，我们关于血清 IL-6 浓度与转换记忆和 CD21 表达 B 细胞频率之间的关联的新发现，以及对 Pneumovax-23 的反应不佳，应在未来的研究中使用更大的样本量来证实。