Giardino Giuliana, Di Matteo Gigliola, Giliani Silvia, Ferrari Simona, Lougaris Vassilios, Badolato Raffaele, Conti Francesca, Romano Roberta, Cicalese Maria Pia, Ricci Silvia, Barzaghi Federica, Marzollo Antonio, Cifaldi Cristina, Montin Davide, Lodi Lorenzo, Cirillo Emilia, Martire Baldassarre, Trizzino Antonio, Sgrulletti Mayla, Moschese Viviana, Comegna Marika, Castaldo Giuseppe, Tommasini Alberto, Azzari Chiara, Cancrini Caterina, Aiuti Alessandro, Pignata Claudio
Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy.
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; Research Unit of Primary Immunodeficiencies, Academic Department of Pediatrics, Bambino Gesù Children's Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy.
J Allergy Clin Immunol. 2025 Apr;155(4):1149-1160. doi: 10.1016/j.jaci.2024.11.030. Epub 2024 Nov 30.
Inborn errors of immunity (IEIs) comprise more than 500 different rare congenital disorders of the immune system and are characterized by susceptibility to infection and immune dysregulation. The significant overlap of the clinical features among the different forms may lead to diagnostic delay. High-throughput sequencing techniques may allow a timely genetic definition. Guidelines for the use and the interpretation of genetic testing produced by the American College of Medical Genetics and Genomics (ACMG) and the European Society of Human Genetics (ESHG) do not cover specifics for their application to IEIs.
The aim of this consensus study was to define the best approach to genetic testing for IEIs.
A panel of experts in the context of the Italian Primary Immunodeficiency Network (IPINet) composed a list of statements that were evaluated by the Delphi method.
The experts recommend that genetic testing for IEIs should be offered to selected patients with warning signs for IEIs and highlight the crucial role of thorough phenotyping and functional tests for the conclusive diagnosis of IEI. Comprehensive educational programs targeted to health care professionals and the public should be developed to increase IEIs awareness and reduce diagnostic delay. Ethical issues should be pondered over the diagnostic advantages of genetic tests requested for diagnostic purposes.
Adherence to guidelines on the use and interpretation of genetic tests for diagnosing IEIs should help limit the inappropriate use of these techniques, thereby reducing the risk of misdiagnosis and patient apprehension regarding inconclusive genetic results.
遗传性免疫缺陷病（IEIs）包含500多种不同的罕见先天性免疫系统疾病，其特征为易感染和免疫失调。不同类型疾病的临床特征有显著重叠，可能导致诊断延迟。高通量测序技术或许能实现及时的基因诊断。美国医学遗传学与基因组学学会（ACMG）和欧洲人类遗传学学会（ESHG）制定的基因检测使用与解读指南未涵盖其在IEIs中的具体应用细节。
本共识研究旨在确定IEIs基因检测的最佳方法。
意大利原发性免疫缺陷网络（IPINet）的专家小组列出了一系列声明，并通过德尔菲法进行评估。
专家们建议，应为有IEIs警示信号的特定患者提供IEIs基因检测，并强调全面的表型分析和功能测试对IEI确诊的关键作用。应制定针对医疗保健专业人员和公众的全面教育计划，以提高对IEIs的认识并减少诊断延迟。对于出于诊断目的要求进行的基因检测的诊断优势，应思考其伦理问题。
遵循诊断IEIs的基因检测使用和解读指南应有助于限制这些技术的不当使用，从而降低误诊风险以及患者对不确定基因检测结果的担忧。
