Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
British Columbia (BC) Children's Hospital, Vancouver, BC, Canada.
Front Immunol. 2022 Feb 22;13:831279. doi: 10.3389/fimmu.2022.831279. eCollection 2022.
Monogenic conditions that disrupt proper development and/or function of the immune system are termed inborn errors of immunity (IEIs), also known as primary immunodeficiencies. Patients with IEIs often suffer from other manifestations in addition to infection, and allergic inflammation is an increasingly recognized feature of these conditions.
We performed a retrospective analysis of IEIs presenting with allergic inflammation as reported in the USIDNET registry. Our inclusion criteria comprised of patients with a reported monogenic cause for IEI where reported lab eosinophil and/or IgE values were available for the patient prior to them receiving potentially curative therapy. Patients were excluded if we were unable to determine the defective gene underlying their IEI. Patients were classified as having eosinophilia or elevated IgE when their record included at least 1 eosinophil count or IgE value that was greater than the age stratified upper limit of normal. We compared the proportion of patients with eosinophilia or elevated IgE with the proportion of samples in a reference population that fall above the upper limit of normal (2.5%).
The query submitted to the USIDNET registry identified 1409 patients meeting inclusion criteria with a monogenic cause for their IEI diagnosis, of which 975 had eosinophil counts and 645 had IgE levels obtained prior to transplantation or gene therapy that were available for analysis. Overall, 18.8% (183/975) of the patients evaluated from the USIDNET registry had eosinophilia and 20.9% (135/645) had an elevated IgE. IEIs caused by defects in 32 genes were found to be significantly associated with eosinophilia and/or an elevated IgE level, spanning 7 of the 10 IEI categories according to the International Union of Immunological Societies classification.
Type 2 inflammation manifesting as eosinophilia or elevated IgE is found in a broad range of IEIs in the USIDNET registry. Our findings suggest that allergic immune dysregulation may be more widespread in IEIs than previously reported.
破坏免疫系统正常发育和/或功能的单基因疾病被称为先天性免疫缺陷（IEI），也称为原发性免疫缺陷。除感染外，IEI 患者常伴有其他表现，过敏炎症是这些疾病的一个日益被认识的特征。
我们对 USIDNET 注册中心报告的以过敏炎症为表现的 IEI 进行了回顾性分析。我们的纳入标准包括：报告存在 IEI 的单基因病因，且患者在接受潜在根治性治疗前，有报告的嗜酸性粒细胞和/或 IgE 值。如果我们无法确定导致 IEI 的缺陷基因，则排除患者。当患者的记录中至少有 1 次嗜酸性粒细胞计数或 IgE 值大于年龄分层正常值上限时，则将其归类为嗜酸性粒细胞增多症或 IgE 升高。我们比较了嗜酸性粒细胞增多症或 IgE 升高患者的比例与参考人群中超过正常值上限（2.5%）的样本比例。
向 USIDNET 注册中心提交的查询确定了 1409 名符合纳入标准的患者，他们的 IEI 诊断具有单基因病因，其中 975 名患者有嗜酸性粒细胞计数，645 名患者有移植或基因治疗前获得的 IgE 水平，可供分析。总体而言，从 USIDNET 注册中心评估的 18.8%（183/975）患者有嗜酸性粒细胞增多症，20.9%（135/645）患者有 IgE 升高。发现 32 个基因缺陷导致的 IEI 与嗜酸性粒细胞增多症和/或 IgE 水平升高显著相关，跨越了国际免疫学会联合会分类的 10 个 IEI 类别中的 7 个。
在 USIDNET 注册中心，表现为嗜酸性粒细胞增多症或 IgE 升高的 2 型炎症存在于广泛的 IEI 中。我们的研究结果表明，过敏免疫失调在 IEI 中的发生率可能比以前报道的更为广泛。
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