Common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA) are two major humoral immunodeficiencies, causing a high rate of early age mortality in children. In order to identifiy the possible factors involved in the pathogenesis of CVID and XLA, recent studies have focused on Toll-like receptors (TLRs) and demonstrate the defects in different TLR pathways in immune cells of CVID and XLA patients. Herein, we measured TLR-4 and TLR-9 RNA levels and consequently TNF-α and IFN-α production in peripheral blood mononuclear cells (PBMCs) of patients with CVID and XLA. Contrary to healthy individuals, TLR-9 expression was not significantly increased after ligand stimulation, whereas ligand-induced TLR-4 expression was not significantly different from that in healthy control PBMCs. Lipopolysaccharide (LPS)-stimulated TNF-α production was significantly reduced in patients compared to controls, whereas IFN-α production was increased in all groups after CpG stimulation without any significant inter-group difference. Our data suggest that defects in TLR-9 activated pathways may be a result of the decreased TLR-9 expression, although TLR-9 is not the only modulator of IFN-α production in these patients. On the other hand, impaired signaling in TLR-4 activated pathways which results in significant reduction in TNF-α production are not related to a defect in TLR-4 expression.

中文翻译：

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常见的可变免疫缺陷症（CVID）和X连锁的丙种球蛋白血症（XLA）中的Toll样受体途径。

常见的可变免疫缺陷（CVID）和X连锁的丙种球蛋白血症（XLA）是两种主要的体液免疫缺陷，导致儿童的早期死亡率很高。为了确定可能与CVID和XLA发病机理有关的因素，最近的研究集中在Toll样受体（TLR），并证明了CVID和XLA患者免疫细胞中不同TLR途径的缺陷。在本文中，我们测量了CVID和XLA患者的外周血单核细胞（PBMC）中TLR-4和TLR-9 RNA的水平，以及由此产生的TNF-α和IFN-α。与健康个体相反，配体刺激后TLR-9表达没有显着增加，而配体诱导的TLR-4表达与健康对照PBMC中的表达没有显着差异。与对照组相比，患者的脂多糖（LPS）刺激的TNF-α产量显着降低，而CpG刺激后所有组的IFN-α产量均增加，而组间无显着差异。我们的数据表明，尽管TLR-9并不是这些患者中唯一的IFN-α产生调节剂，但TLR-9激活途径的缺陷可能是TLR-9表达降低的结果。另一方面，导致TNF-α产生显着减少的TLR-4激活途径中的信号传导受损与TLR-4表达缺陷无关。我们的数据表明，尽管TLR-9并不是这些患者中唯一的IFN-α产生调节剂，但TLR-9激活途径的缺陷可能是TLR-9表达降低的结果。另一方面，导致TNF-α产生显着减少的TLR-4激活途径中的信号传导受损与TLR-4表达缺陷无关。我们的数据表明，尽管TLR-9不是这些患者中唯一的IFN-α产生调节剂，但TLR-9激活途径的缺陷可能是TLR-9表达降低的结果。另一方面，导致TNF-α产生显着减少的TLR-4激活途径中的信号传导受损与TLR-4表达缺陷无关。