Genomic profiling at a single center cracks the code in inborn errors of immunity.

IF 3.2 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Alessandro Andriano, Vanessa Desantis, Carolina Marasco, Antonio Marzollo, Silvia Bresolin, Nicoletta Resta, Lucia Di Marzo, Fabrizio Pappagallo, Antonella Mascolo, Ingrid Catalina Caradonna, Simona D'Amore, Angelo Vacca, Antonio Giovanni Solimando
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Abstract

Inborn errors of immunity (IEI) entail a diverse group of disorders resulting from hereditary or de novo mutations in single genes, leading to immune dysregulation. This study explores the clinical utility of next-generation sequencing (NGS) techniques in diagnosing monogenic immune defects. Eight patients attending the immunodeficiency clinic and with unclassified antibody deficiency were included in the analysis. Clinical records, immune characteristics, and family histories were reviewed, and a target gene panel (TGP) sequencing was performed to identify pathogenic variants. TGPs identified seven variants in TNFRSF13B (TACI), CARMIL2, STAT1, STAT3, and ORAI1 genes. These findings provided definitive diagnoses and proper prognostic assessment. Patients exhibited a wide range of clinical manifestations, including recurrent infections, autoimmune cytopenias, and organ-specific complications. The genetic diversity observed highlights the importance of genetic testing in diagnosing IEIs and tailoring treatments. This study underscores the role of TGPs in diagnosing IEIs, revealing significant genetic heterogeneity and phenotypic variability. They offer a precise tool for identifying underlying genetic defects, facilitating personalized medicine approaches, and eventually improving patient outcomes. The findings emphasize the need for comprehensive genetic testing to uncover novel pathogenic variants, enhancing our understanding of immune system dysfunction. NGS is a critical tool for the management of IEI, enabling precise diagnosis and personalized treatment strategies. Despite resource limitations, the progressive affordability is likely to expand its clinical utility, ultimately improving patient care and advancing the field of immunology. In the meantime, accurate phenotypic assessment is essential for resource optimization and case prioritization.

单一中心的基因组分析破解了先天免疫错误的密码。
先天性免疫错误(IEI)是由单一基因的遗传或新生突变引起的多种疾病,导致免疫失调。本研究探讨了下一代测序(NGS)技术在诊断单基因免疫缺陷中的临床应用。8名在免疫缺陷诊所就诊的未分类抗体缺乏患者被纳入分析。研究人员回顾了临床记录、免疫特征和家族史,并进行了靶基因面板(TGP)测序以确定致病变异。TGPs鉴定出TNFRSF13B (TACI)、CARMIL2、STAT1、STAT3和ORAI1基因中的7个变异。这些发现提供了明确的诊断和适当的预后评估。患者表现出广泛的临床表现,包括复发性感染、自身免疫性细胞减少和器官特异性并发症。观察到的遗传多样性突出了基因检测在诊断肠感染和定制治疗方面的重要性。这项研究强调了TGPs在诊断IEIs中的作用,揭示了显著的遗传异质性和表型变异性。它们提供了一种精确的工具来识别潜在的遗传缺陷,促进个性化的医疗方法,并最终改善患者的治疗效果。研究结果强调需要全面的基因检测来发现新的致病变异,增强我们对免疫系统功能障碍的理解。NGS是管理IEI的关键工具,可实现精确诊断和个性化治疗策略。尽管资源有限,渐进式可负担性很可能扩大其临床应用,最终改善患者护理和推进免疫学领域。同时,准确的表型评估对于资源优化和病例优先排序至关重要。
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来源期刊
Internal and Emergency Medicine
Internal and Emergency Medicine 医学-医学:内科
CiteScore
7.20
自引率
4.30%
发文量
258
审稿时长
6-12 weeks
期刊介绍: Internal and Emergency Medicine (IEM) is an independent, international, English-language, peer-reviewed journal designed for internists and emergency physicians. IEM publishes a variety of manuscript types including Original investigations, Review articles, Letters to the Editor, Editorials and Commentaries. Occasionally IEM accepts unsolicited Reviews, Commentaries or Editorials. The journal is divided into three sections, i.e., Internal Medicine, Emergency Medicine and Clinical Evidence and Health Technology Assessment, with three separate editorial boards. In the Internal Medicine section, invited Case records and Physical examinations, devoted to underlining the role of a clinical approach in selected clinical cases, are also published. The Emergency Medicine section will include a Morbidity and Mortality Report and an Airway Forum concerning the management of difficult airway problems. As far as Critical Care is becoming an integral part of Emergency Medicine, a new sub-section will report the literature that concerns the interface not only for the care of the critical patient in the Emergency Department, but also in the Intensive Care Unit. Finally, in the Clinical Evidence and Health Technology Assessment section brief discussions of topics of evidence-based medicine (Cochrane’s corner) and Research updates are published. IEM encourages letters of rebuttal and criticism of published articles. Topics of interest include all subjects that relate to the science and practice of Internal and Emergency Medicine.
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