Barbati Federica, Lodi Lorenzo, Boscia Silvia, Cortimiglia Martina, Calistri Elisa, Quaranta Francesca, Maggi Laura, Mazzoni Alessio, Palterer Boaz, Annunziato Francesco, Azzari Chiara, Ricci Silvia
Pediatrics and Neonatology Unit, Santo Stefano Hospital, USL Toscana Centro, Prato, Italy.
Department of Neurofarba, University of Florence, Florence, Italy.
Eur J Immunol. 2025 Mar;55(3):e202451433. doi: 10.1002/eji.202451433.
Common variable immunodeficiency (CVID) represents an "umbrella" diagnosis due to its clinical and immunological heterogeneity. The primary objective of this study was to describe a cohort of CVID pediatric subjects from clinical, immunological, and genetic viewpoints. Secondary, we propose a model for prioritizing genetic investigations in these patients. Thirty-four patients with CVID followed at Meyer Children's Hospital, IRCSS, were enrolled. Whole exome sequencing was performed according to the latest International Union of Immunological Societies 2022 update. Genetic variants were identified in 16 patients (47%), including known variants in SLC39A7, PRKCD, STAT3, NFKB1, PIK3R1, PLCG2, RFXANK, PRKDC, TNFRSF13B, and novel variants in SPI1, NFKB1, NFKB2. Comparing the Gene+ and Gene- cohorts, we demonstrated that a monogenic cause is more likely to be found in cases of early disease onset, positive family history, autoimmunity, lymphoproliferation, and specific immunological alterations. Using these criteria, we developed a pediatric monogenic CVID (Mo-CVID) score to hypothesize when a CVID pediatric patient is more likely to carry a genetic mutation. A scoring system such as the Mo-CVID score could help physicians prioritize genetic testing. Genetic analysis in CVID patients can help stratify patients into different disease entities to predict complications and prognosis, ensure appropriate genetic counseling, and personalize treatment.
常见变异型免疫缺陷（CVID）因其临床和免疫异质性而属于一种“综合性”诊断。本研究的主要目的是从临床、免疫和遗传学角度描述一组CVID儿科患者。其次，我们提出了一个对这些患者进行基因检测优先级排序的模型。招募了34名在迈耶儿童医院（IRCSS）接受治疗的CVID患者。根据国际免疫学会联盟2022年的最新更新进行了全外显子组测序。在16名患者（47%）中鉴定出基因变异，包括SLC39A7、PRKCD、STAT3、NFKB1、PIK3R1、PLCG2、RFXANK、PRKDC、TNFRSF13B中的已知变异，以及SPI1、NFKB1、NFKB2中的新变异。比较基因阳性和基因阴性队列，我们发现单基因病因在疾病早发、家族史阳性、自身免疫、淋巴细胞增殖和特定免疫改变的病例中更有可能被发现。利用这些标准，我们制定了一个儿科单基因CVID（Mo-CVID）评分，以推测CVID儿科患者何时更有可能携带基因突变。像Mo-CVID评分这样的评分系统可以帮助医生确定基因检测的优先级。对CVID患者进行基因分析有助于将患者分层为不同的疾病实体，以预测并发症和预后，确保适当的遗传咨询，并实现个性化治疗。
