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-1ß 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-1ß 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-1ß 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-1ß 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^low expressing B cells were found. Conclusion: Secretion of IL-6 and IL-lß 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^low 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.

中文翻译：

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白细胞介素-1β和白细胞介素-6常见免疫功能低下及其与B细胞亚型的关系以及对肺炎克雷伯氏疫苗的反应。

简介：常见可变免疫缺陷症（CVID）是原发性免疫缺陷的最常见症状形式。当前的研究数据显示，CVID患者的B细胞，TLR和细胞因子谱改变。这项研究的目的是确定CVID患者对TLR刺激的反应以及这些细胞因子与B细胞亚型和对Pneumovax-23疫苗反应的相关性中IL-1ß和IL-6的水平。方法：CIVD患者的外周血单核细胞在有和没有TLR2和TLR4激动剂以及特定抑制剂（包括脂多糖（LPS），脂蛋白回声（LTA）和OxPAPC）的刺激下进行。通过ELISA评估不同治疗组的IL-1ß和IL-6水平。最后，评估了不同亚型B细胞和对Pneumovax-23疫苗的反应类型之间的细胞因子水平相关性。结果：CVID患者的IL-6和IL-1ß分泌显着减少（p = 0.015和p = 0.019），但是TLR2和TLR4的配体结合导致IL-6和IL-1ß产生显着增加。Pneumovax-23低反应患者中IL-6显着降低（p = 0.05），并且IL-6的浓度与转换记忆和CD21的数量之间存在显着相关性发现^低表达的B细胞。结论：CVID患者的IL-6和IL-1β分泌被消除。但是，TLR2和TLR4对它们的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 TLR的这一特征导致细胞因子分泌的改善。另外，我们关于血清IL-6的关联浓度以及记忆转换频率和CD21^低表达B细胞频率以及对Pneumovax-23的不良反应的新发现应通过将来使用更大的样本量来证实学习。