常见的可变免疫缺陷临床表现是由杂合子NFKB1变异的存在和类型决定的。

IF 8.2 1区 医学 Q1 ALLERGY
Jie Yin MD , Kevin M. Hayes BS , Mei-Sing Ong PhD , Joseph P. Mizgerd ScD , Charlotte Cunningham-Rundles MD, PhD , Isabel Dominguez PhD , Sara Barmettler MD , Jocelyn R. Farmer MD, PhD , Paul J. Maglione MD, PhD
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引用次数: 0

摘要

背景:NFKB1编码p105, p105被加工成p50介导NF-κB信号转导。尽管NF-κB是炎症的核心驱动因素,杂合型NFKB1变异被认为是常见变异性免疫缺陷(CVID)最常见的单基因病因,但很少有研究探讨NFKB1变异如何影响CVID的临床过程或炎症。目的:我们利用具有和不具有杂合NFKB1变异的CVID患者的区域队列来评估这些变异的存在如何影响CVID的临床和炎症特征。方法:我们比较了15例杂合子NFKB1变异CVID患者和77例遗传不明的CVID患者的临床并发症、免疫学特征和血浆细胞因子水平。我们还评估了移码或无义NFKB1变异体与错义NFKB1变异体CVID患者之间的差异。结果:我们发现带有杂合子NFKB1变异的CVID患者自身免疫性疾病、支气管扩张、胃肠道感染、炎症性肠病(IBD)和血浆细胞因子增加。与错义NFKB1变异体相比,移码或无义NFKB1变异体CVID患者的这些发现更为明显,包括单核细胞升高。结论:在一个区域队列中,杂合NFKB1变异与CVID临床病程恶化和血液炎症证据增加有关。移码或无义NFKB1变异体的CVID患者的非感染性并发症和外周单核细胞比错义NFKB1变异体的患者有更显著的增加。CVID患者中存在致病性NFKB1变异可能会加重病程,需要更密切的监测。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Common Variable Immunodeficiency Clinical Manifestations Are Shaped by Presence and Type of Heterozygous NFKB1 Variants

Background

NFKB1 encodes p105, which is processed to p50 to mediate canonical nuclear factor-κB (NF-κB) signaling. Although NF-κB is a central driver of inflammation and heterozygous NFKB1 variants are considered the most common monogenic etiologies of common variable immunodeficiency (CVID), few studies have explored how NFKB1 variants shape clinical course or inflammation in CVID.

Objective

We leveraged a regional cohort of patients with CVID with and without heterozygous NFKB1 variants to assess how clinical and inflammatory features of CVID are shaped by the presence of these variants.

Methods

We compared clinical complications, immunologic features, and plasma cytokine levels of 15 patients with CVID with heterozygous NFKB1 variants and 77 genetically undefined patients with CVID from the same referral base. We also assessed differences between patients with CVID with frameshift or nonsense NFKB1 variants compared with those with missense NFKB1 variants.

Results

We found patients with CVID with heterozygous NFKB1 variants to have increased autoimmune disease, bronchiectasis, gastrointestinal infections, inflammatory bowel disease, and plasma cytokines. These findings were more pronounced and included elevation of monocytes in patients with CVID with frameshift or nonsense NFKB1 variants relative to those with missense NFKB1 variants.

Conclusions

In a regional cohort, heterozygous NFKB1 variants were associated with worsened CVID clinical course and increased evidence of inflammation in the blood. Patients with CVID with frameshift or nonsense NFKB1 variants had more significant increases in noninfectious complications and peripheral monocytes than those with missense NFKB1 variants. Presence of pathogenic NFKB1 variants in patients with CVID may worsen the disease course and warrant closer monitoring.
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来源期刊
CiteScore
11.10
自引率
9.60%
发文量
683
审稿时长
50 days
期刊介绍: JACI: In Practice is an official publication of the American Academy of Allergy, Asthma & Immunology (AAAAI). It is a companion title to The Journal of Allergy and Clinical Immunology, and it aims to provide timely clinical papers, case reports, and management recommendations to clinical allergists and other physicians dealing with allergic and immunologic diseases in their practice. The mission of JACI: In Practice is to offer valid and impactful information that supports evidence-based clinical decisions in the diagnosis and management of asthma, allergies, immunologic conditions, and related diseases. This journal publishes articles on various conditions treated by allergist-immunologists, including food allergy, respiratory disorders (such as asthma, rhinitis, nasal polyps, sinusitis, cough, ABPA, and hypersensitivity pneumonitis), drug allergy, insect sting allergy, anaphylaxis, dermatologic disorders (such as atopic dermatitis, contact dermatitis, urticaria, angioedema, and HAE), immunodeficiency, autoinflammatory syndromes, eosinophilic disorders, and mast cell disorders. The focus of the journal is on providing cutting-edge clinical information that practitioners can use in their everyday practice or to acquire new knowledge and skills for the benefit of their patients. However, mechanistic or translational studies without immediate or near future clinical relevance, as well as animal studies, are not within the scope of the journal.
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