Fatal Systemic Granulomatous Disease Associated with Vaccine-Derived Rubella Virus in AIOLOS-Associated Immunodeficiency.

IF 4.1 2区医学 Q1 IMMUNOLOGY

Journal of Clinical Immunology Pub Date : 2026-02-26 DOI:10.1007/s10875-026-01990-7

Linda Zhou, Hye Sun Kuehn, Dayna Gager, Agustin A Gil Silva, Ludmila M Perelygina, LiJuan Hao, Min-Hsin Chen, Julie E Niemela, Jennifer L Stoddard, Matthew Helm, Karolyn Wanat, Kathleen Sullivan, Galen Foulke, Thomas H Leung, Sergio D Rosenzweig, Misha Rosenbach

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Abstract

We present a case of disseminated granulomatous disease associated with live attenuated vaccine-derived rubella virus (VDRV) in an immunodeficient patient who subsequently developed fatal multi-organ failure, including neurological deficits, with VDRV detected in the cerebrospinal fluid. Posthumous genetic analysis found a heterozygous missense mutation in IKZF3, a gene where haploinsufficiency is linked to immunodeficiency and immune dysregulation. Functional studies demonstrated that this mutation decreases AIOLOS protein stability and half-life, and family members carrying the same mutation exhibited decreased AIOLOS levels. This report underscores the importance of considering persistent rubella virus (RuV) infection in patients with cutaneous granulomatous lesions and highlights the need for comprehensive evaluation to uncover potential underlying immunodeficiencies, which could inform and optimize individualized treatment strategies.

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aios相关免疫缺陷中与疫苗衍生风疹病毒相关的致命性全身性肉芽肿病

我们报告一例与减毒活疫苗衍生风疹病毒（VDRV）相关的弥散性肉芽肿病，患者为免疫缺陷患者，随后发展为致命的多器官功能衰竭，包括神经功能缺损，脑脊液中检测到VDRV。死后遗传分析发现IKZF3基因存在杂合错义突变，该基因的单倍不足与免疫缺陷和免疫失调有关。功能研究表明，该突变降低了AIOLOS蛋白的稳定性和半衰期，携带相同突变的家族成员表现出AIOLOS水平降低。本报告强调了考虑皮肤肉芽肿病变患者持续性风疹病毒（RuV）感染的重要性，并强调了需要进行全面评估以发现潜在的潜在免疫缺陷，这可以为个性化治疗策略提供信息和优化。

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来源期刊

Journal of Clinical Immunology 医学-免疫学

CiteScore

12.20

自引率

9.90%

发文量

218

审稿时长

2 months

期刊介绍： The Journal of Clinical Immunology publishes impactful papers in the realm of human immunology, delving into the diagnosis, pathogenesis, prognosis, or treatment of human diseases. The journal places particular emphasis on primary immunodeficiencies and related diseases, encompassing inborn errors of immunity in a broad sense, their underlying genotypes, and diverse phenotypes. These phenotypes include infection, malignancy, allergy, auto-inflammation, and autoimmunity. We welcome a broad spectrum of studies in this domain, spanning genetic discovery, clinical description, immunologic assessment, diagnostic approaches, prognosis evaluation, and treatment interventions. Case reports are considered if they are genuinely original and accompanied by a concise review of the relevant medical literature, illustrating how the novel case study advances the field. The instructions to authors provide detailed guidance on the four categories of papers accepted by the journal.