Division of Pediatric Hemato-Oncology, Department of Pediatrics and Adolescent Medicine, Research Unit for Pediatric Hematology and Immunology, Medical University Graz, Graz, Austria.
Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Central Facility Biobanking, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
J Allergy Clin Immunol Pract. 2019 Jul-Aug;7(6):1763-1770. doi: 10.1016/j.jaip.2019.02.004. Epub 2019 Feb 15.
Patient registries are instrumental for clinical research in rare diseases. They help to achieve a sufficient sample size for epidemiological and clinical research and to assess the feasibility of clinical trials. The European Society for Immunodeficiencies (ESID) registry currently comprises information on more than 25,000 patients with inborn errors of immunity (IEI). The prerequisite of a patient to be included into the ESID registry is an IEI either defined by a defect in a gene included in the disease classification of the international union of immunological societies, or verified by applying clinical criteria. Because a relevant number of patients, including those with common variable immunodeficiency (CVID), representing the largest group of patients in the registry, remain without a genetic diagnosis, consensus on classification of these patients is mandatory. Here, we present clinical criteria for a large number of IEI that were designed in expert panels with an external review. They were implemented for novel entries and verification of existing data sets from 2014, yielding a substantial refinement. For instance, 8% of adults and 27% of children with CVID (176 of 1704 patients) were reclassified to 22 different immunodeficiencies, illustrating progress in genetics, but also the previous lack of standardized disease definitions. Importantly, apart from registry purposes, the clinical criteria are also helpful to support treatment decisions in the absence of a genetic diagnosis or in patients with variants of unknown significance.
患者登记处是罕见病临床研究的重要工具。它们有助于为流行病学和临床研究获得足够的样本量，并评估临床试验的可行性。欧洲免疫缺陷学会（ESID）登记处目前包含了超过 25000 名先天性免疫缺陷（IEI）患者的信息。患者被纳入 ESID 登记处的前提是其存在基因缺陷，这些基因缺陷被包含在国际免疫学会联盟的疾病分类中，或者通过应用临床标准得到验证。由于相当数量的患者，包括最常见的一组患者——普通可变免疫缺陷（CVID）患者，仍然没有遗传诊断，因此对这些患者进行分类的共识是强制性的。在这里，我们提出了大量 IEI 的临床标准，这些标准是由专家小组设计的，并进行了外部审查。从 2014 年开始，这些标准被用于新的条目，并对现有数据集进行验证，从而得到了实质性的改进。例如，1704 名 CVID 患者中有 8%的成年人和 27%的儿童（176 名）被重新分类为 22 种不同的免疫缺陷，这说明了遗传学的进步，但也说明了以前缺乏标准化的疾病定义。重要的是，除了登记处的目的外，这些临床标准在缺乏遗传诊断或在患者存在未知意义的变异体的情况下，也有助于支持治疗决策。
