X 连锁阿加球蛋白血症中 TLR 信号相关基因表达的失调:基因型-表型与疾病表达相关性的意义。

IF 4.7 3区 医学 Q2 IMMUNOLOGY Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-08-08 DOI:10.1159/000540082
Marcelo Teocchi, Thaís de Andrade Eugênio, Lia Furlaneto Marega, Isabella Quinti, Maria Marluce Dos Santos Vilela
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引用次数: 0

摘要

引言 在X连锁丙种球蛋白血症(XLA)中,BTK变体的多样性使基因型与表型相关性的研究变得复杂。由于 BTK 负向调节收费样受体(TLR),我们研究了不同的 BTK 突变类型是否会选择性地调节 TLR 通路,从而影响疾病的表达。方法 我们使用 RT-qPCR 对 BTK 突变错义(n=3)和无义(n=5)的 XLA 患者以及健康对照组(n=17)中的 10 个 TLR 信号相关基因进行了定量分析。结果 BTK、IRAK2、PIK3R4、REL、TFRC和UBE2N主要被下调,而RIPK2、TLR3、TLR10和TLR6则表现出不同的调控。错义 XLA 组 IRAK2、PIK3R4、REL 和 TFRC 明显下调,TLR3 和/或 TLR6 上调。结论 TLR3、TLR6 和 TLR10 的低表达可能会增加对感染的易感性,而高表达可能会导致慢性炎症,如关节炎或炎症性肠病。我们的发现揭示了一些 XLA 患者的重要炎症特征,即使在最佳治疗条件下也是如此。
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Dysregulation of Toll-Like Receptor Signaling-Associated Gene Expression in X-Linked Agammaglobulinemia: Implications for Correlations Genotype-Phenotype and Disease Expression.

Introduction: In X-linked agammaglobulinemia (XLA), the diversity of BTK variants complicates the study of genotype-phenotype correlations. Since BTK negatively regulates toll-like receptors (TLRs), we investigated if distinct BTK mutation types selectively modulate TLR pathways, affecting disease expression.

Methods: Using reverse transcription-quantitative polymerase chain reaction, we quantified ten TLR signaling-related genes in XLA patients with missense (n = 3) and nonsense (n = 5) BTK mutations and healthy controls (n = 17).

Results: BTK, IRAK2, PIK3R4, REL, TFRC, and UBE2N were predominantly downregulated, while RIPK2, TLR3, TLR10, and TLR6 showed variable regulation. The missense XLA group exhibited significant downregulation of IRAK2, PIK3R4, REL, and TFRC and upregulation of TLR3 and/or TLR6.

Conclusion: Hypo-expression of TLR3, TLR6, and TLR10 may increase susceptibility to infections, while hyper-expression might contribute to chronic inflammatory conditions like arthritis or inflammatory bowel disease. Our findings shed light on the important inflammatory component characteristic of some XLA patients, even under optimal therapeutic conditions.

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来源期刊
Journal of Innate Immunity
Journal of Innate Immunity 医学-免疫学
CiteScore
10.50
自引率
1.90%
发文量
35
审稿时长
7.5 months
期刊介绍: The ''Journal of Innate Immunity'' is a bimonthly journal covering all aspects within the area of innate immunity, including evolution of the immune system, molecular biology of cells involved in innate immunity, pattern recognition and signals of ‘danger’, microbial corruption, host response and inflammation, mucosal immunity, complement and coagulation, sepsis and septic shock, molecular genomics, and development of immunotherapies. The journal publishes original research articles, short communications, reviews, commentaries and letters to the editors. In addition to regular papers, some issues feature a special section with a thematic focus.
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