Department of Tranzo, TSB, Tilburg University, Tilburg, the Netherlands.
Department of Pediatrics, Amalia Children's hospital, Nijmegen, the Netherlands.
PLoS One. 2022 Mar 25;17(3):e0266083. doi: 10.1371/journal.pone.0266083. eCollection 2022.
Primary antibody deficiencies (PADs) without an identified monogenetic origin form the largest and most heterogeneous group of primary immunodeficiencies. These patients often remain undiagnosed for years and many present to medical attention in adulthood after several infections risking structural complications. Not much is known about their treatment, comorbidities, or prognosis, nor whether the various immunological forms (decreased total IgG, IgG subclass(es), IgM, IgA, specific antibody responses, alone or in combination(s)) should be considered as separate, clearly definable subgroups. The unclassified primary antibody deficiency (unPAD) study aims to describe in detail all PAD patients without an identified specific monogenetic defect regarding their demographical, clinical, and immunological characteristics at presentation and during follow-up. In constructing these patterns, the unPAD study aims to reduce the number of missed and unidentified PAD patients in the future. In addition, this study will focus on subclassifying unPAD to support the identification of patients at higher risk for infection or immune dysregulation related complications, enabling the development of personalized follow-up and treatment plans.
We present a protocol for a multicenter observational cohort study using the ESID online Registry. Patients of all ages who have given informed consent for participation in the ESID online Registry and fulfill the ESID Clinical Working Definitions for 'unclassified antibody deficiency', 'deficiency of specific IgG', 'IgA with IgG subclass deficiency', 'isolated IgG subclass deficiency', 'selective IgM deficiency', 'selective IgA deficiency' or 'common variable immunodeficiency' will be included. For all patients, basic characteristics can be registered at first registration and yearly thereafter in level 1 forms. Detailed characteristics of the patients can be registered in level 2 forms. Consecutive follow-up forms can be added indefinitely. To ensure the quality of the collected data, all data will be fully monitored before they are exported from the ESID online Registry for analysis. Outcomes will be the clinical and immunological characteristics of unPAD at presentation and during follow-up. Subgroup analyses will be made based on demographical, clinical and immunological characteristics.
没有明确单基因起源的原发性抗体缺陷（PAD）构成了原发性免疫缺陷中最大和最多样化的一组。这些患者通常多年未被诊断，许多人在成年后因多次感染而出现结构并发症，从而导致出现各种并发症后才到医疗机构就诊。对于他们的治疗、合并症或预后，以及各种免疫形式（总 IgG、IgG 亚类、IgM、IgA、特异性抗体反应，单独或组合）是否应被视为单独的、可明确界定的亚组，人们知之甚少。未分类的原发性抗体缺陷（unPAD）研究旨在详细描述所有无明确特定单基因缺陷的 PAD 患者，包括其在就诊时和随访期间的人口统计学、临床和免疫学特征。在构建这些模式时，unPAD 研究旨在减少未来漏诊和未确诊的 PAD 患者数量。此外，本研究还将侧重于将 unPAD 分类，以支持识别感染或免疫失调相关并发症风险较高的患者，从而制定个性化的随访和治疗计划。
我们提出了一项基于 ESID 在线注册中心的多中心观察性队列研究方案。所有年龄的患者，只要他们对参与 ESID 在线注册中心表示知情同意并符合 ESID 临床工作定义的“未分类抗体缺陷”、“特定 IgG 缺乏症”、“IgA 与 IgG 亚类缺乏症”、“孤立性 IgG 亚类缺乏症”、“选择性 IgM 缺乏症”、“选择性 IgA 缺乏症”或“常见可变免疫缺陷”，将被纳入研究。对于所有患者，基本特征可在首次登记时登记，并在之后每年的 1 级表格中登记。患者的详细特征可在 2 级表格中登记。可无限期添加连续随访表格。为确保收集数据的质量，所有数据在从 ESID 在线注册中心导出进行分析之前都将得到全面监测。研究的结果将是 unPAD 患者在就诊时和随访期间的临床和免疫学特征。将根据人口统计学、临床和免疫学特征进行亚组分析。
