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

IF 2.2 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Laleh Sharifi, Asghar Aghamohammadi, Nima Rezaei, Reza Yazdani, Farhad Rezaei, Saied Bokaie, Farzaneh Tofighi Zavareh, Fatemeh Kiaee, Ali N Kamali, Gholamreza Azizi, Abbas Mirshafiey
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引用次数: 2

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 CD21low 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 CD21low 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.

白细胞介素-1β和白细胞介素-6在常见变异性免疫缺陷中的作用及其与B细胞亚型的关系以及对肺炎-23疫苗的应答
简介:共同可变免疫缺陷(CVID)是原发性免疫缺陷最常见的症状形式。目前的研究数据显示,CVID患者的B细胞、tlr和细胞因子谱发生了改变。本研究的目的是确定CVID患者对TLRs刺激的IL-1β和IL-6水平,以及这些细胞因子与B细胞亚型和对Pneumovax-23疫苗应答的关系。方法:分别用TLR2和TLR4激动剂及脂多糖(LPS)、脂质胆固醇(LTA)、OxPAPC等特异性抑制剂刺激CIVD患者外周血单个核细胞。采用酶联免疫吸附试验(ELISA)检测不同治疗组大鼠血清IL-1β、IL-6水平。最后,评估了不同B细胞亚型和对Pneumovax-23疫苗反应类型之间细胞因子水平的相关性。结果:CVID患者IL-6和IL-1β分泌明显减少(p = 0.015和p = 0.019),但TLR2和TLR4配体结合导致IL-6和IL-1β分泌显著增加。IL-6在Pneumovax-23低反应患者中显著降低(p = 0.05), IL-6浓度与开关记忆和CD21low表达的B细胞数量呈显著相关。结论:CVID患者IL-6、IL-1β分泌明显减少。然而,TLR2和TLR4对其同源配体的刺激反应过度,导致分泌更高水平的促炎细胞因子。与基线水平相比,CVID TLRs的这一特征导致细胞因子分泌的改善。此外,我们关于血清IL-6浓度与切换记忆和CD21low表达B细胞的频率以及对Pneumovax-23的不良反应的关联的新发现应该在未来的研究中通过使用更大的样本量来证实。
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来源期刊
European cytokine network
European cytokine network 生物-免疫学
CiteScore
5.70
自引率
0.00%
发文量
5
审稿时长
6 months
期刊介绍: The journal that brings together all areas of work involving cytokines. European Cytokine Network is an electronic journal that publishes original articles and abstracts every quarter to provide an essential bridge between researchers and clinicians with an interest in this cutting-edge field. The journal has become a must-read for specialists in the field thanks to its swift publication and international circulation. The journal is referenced in several databases, including Medline, which is testament to its scientific quality.
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