Common variable immunodeficiency due to a novel variant in NFKB1 with a neonatal presentation of parechovirus meningitis and sepsis-like illness.

IF 2.5 4区 医学 Q3 ALLERGY
Allergologia et immunopathologia Pub Date : 2025-05-01 eCollection Date: 2025-01-01 DOI:10.15586/aei.v53i3.1307
Aleksandra Szczawińska-Popłonyk, Natalia Popłonyk, Katarzyna Bernat-Sitarz, Katarzyna Jończyk-Potoczna, Agnieszka Pollak
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引用次数: 0

Abstract

Monoallelic variants in the nuclear factor kappa B 1 (NFKB1) gene reinforce the functional haploinsufficiency causing immunodeficiency with marked individual and intrafamilial variability in genotype-phenotype correlations. The leading clinical manifestations of NF-κB1 deficiency are recurrent infections and immune dysregulation disorders with autoinflammatory and lymphoproliferative disease. The reported patient initially presented with a neonatal sepsis-like illness with meningitis because of a parechovirus infection. The diagnosis of an inborn error of immunity, common variable immunodeficiency (CVID), was established based on hypogammaglobulinemia, impaired antibody response to vaccines, IgG subclass deficiency, and low numbers of switched memory B cells. Molecular genetic testing using trio whole exome sequencing was done to define the background of the presenting phenotype, and it revealed a novel heterozygous variant of NFKB1. Viral meningitis and sepsis-like illness are unusual, previously unreported, infectious complications in NF-κB1 deficiency. The transcriptional NF-κB1 regulatory effect on different target gene repertoires and numerous processes including immune and inflammatory responses may indiacte the vulnerability of deficient patients to severe viral infections. This case report exemplifies the advancement of immunogenetics paving the way for the transition from the initial era of clinical recognition to the era of molecular diagnosis of the pediatric CVID.

常见的可变免疫缺陷是由于NFKB1的一种新变异,新生儿表现为肺炎病毒脑膜炎和败血症样疾病。
核因子κ b1 (NFKB1)基因的单等位变异加强了功能性单倍缺陷,导致免疫缺陷,在基因型-表型相关性中具有显著的个体和家族内变异性。NF-κB1缺乏的主要临床表现为反复感染和自身炎症性和淋巴细胞增生性疾病的免疫失调。报告的患者最初表现为新生儿败血症样疾病并脑膜炎,因为肺炎病毒感染。基于低丙种球蛋白血症、对疫苗的抗体反应受损、IgG亚类缺乏和低数量的转换记忆B细胞,诊断为先天性免疫缺陷,常见可变免疫缺陷(CVID)。利用三重奏全外显子组测序进行分子遗传学检测以确定呈现表型的背景,并揭示了NFKB1的一种新的杂合变异。病毒性脑膜炎和败血症样疾病是NF-κB1缺乏症的罕见且未见报道的感染性并发症。转录NF-κB1对不同靶基因库和包括免疫和炎症反应在内的众多过程的调节作用可能表明缺陷患者对严重病毒感染的易感性。本病例报告体现了免疫遗传学的进步,为儿童CVID从最初的临床识别时代过渡到分子诊断时代铺平了道路。
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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
131
审稿时长
6-12 weeks
期刊介绍: Founded in 1972 by Professor A. Oehling, Allergologia et Immunopathologia is a forum for those working in the field of pediatric asthma, allergy and immunology. Manuscripts related to clinical, epidemiological and experimental allergy and immunopathology related to childhood will be considered for publication. Allergologia et Immunopathologia is the official journal of the Spanish Society of Pediatric Allergy and Clinical Immunology (SEICAP) and also of the Latin American Society of Immunodeficiencies (LASID). It has and independent international Editorial Committee which submits received papers for peer-reviewing by international experts. The journal accepts original and review articles from all over the world, together with consensus statements from the aforementioned societies. Occasionally, the opinion of an expert on a burning topic is published in the "Point of View" section. Letters to the Editor on previously published papers are welcomed. Allergologia et Immunopathologia publishes 6 issues per year and is included in the major databases such as Pubmed, Scopus, Web of Knowledge, etc.
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