Diagnostics, PATH, Seattle, WA, USA.
Department of Immunology, Pasteur Institute of Tunis, Tunis, Tunisia.
J Clin Immunol. 2022 Feb;42(2):394-403. doi: 10.1007/s10875-021-01179-0. Epub 2021 Nov 27.
No rapid diagnostic test exists to screen individuals for primary antibody deficiencies (PAD) at or near the point of care. In settings at risk for polio where live oral polio vaccine is utilized, undiagnosed PAD patients and cases with delayed diagnosis constitute a potential reservoir for neurovirulent polioviruses, undermining polio eradication. This research aimed to develop a rapid screening test suited for use in resource-limited settings to identify individuals with low immunoglobulin G (IgG) levels, enabling early diagnosis and appropriate treatment.
Three prototype tests distinguishing low and normal IgG levels were evaluated with a blinded panel of serum/plasma specimens from 32 healthy controls and 86 primary immunodeficiency-confirmed patients with agammaglobulinemia, common variable immunodeficiency, and hyper-IgM syndrome, including 57 not receiving IgG therapy. Prototype tests were compared to laboratory reference and clinical case definition.
The leading prototype correctly identified 32 of 32 healthy controls. Among primary antibody deficiency patients not receiving IgG treatment, 17 of 19 agammaglobulinemia, 7 of 24 common variable immunodeficiency, and 5 of 14 hyper-IgM were correctly identified by the prototype, with 67% agreement with the reference assay.
The Rapid IgG Screen (RIgGS) test can differentiate between low IgG levels associated with agammaglobulinemia and normal IgG antibody levels. Differentiating CVID and hyper IgM was challenging due to the wide range in IgG levels and influence of high IgM. This test can facilitate the identification of patients with primary antibody deficiencies and support polio surveillance initiatives.
目前尚无用于在现场或接近现场筛查原发性抗体缺陷（PAD）的快速诊断检测方法。在使用口服脊髓灰质炎活疫苗的存在脊髓灰质炎风险的环境中，未确诊的 PAD 患者和延迟诊断的病例构成了神经毒性脊髓灰质炎病毒的潜在储库，破坏了脊髓灰质炎的消除。本研究旨在开发一种适合资源有限环境使用的快速筛选检测方法，以识别免疫球蛋白 G（IgG）水平较低的个体，从而能够进行早期诊断和适当治疗。
使用盲法评估了三个区分低 IgG 水平和正常 IgG 水平的原型检测方法，该方法使用了来自 32 名健康对照者和 86 名原发性免疫缺陷确诊为无丙种球蛋白血症、常见可变免疫缺陷和高 IgM 综合征的患者的血清/血浆标本，包括 57 名未接受 IgG 治疗的患者。原型检测与实验室参考和临床病例定义进行了比较。
领先的原型正确识别了 32 名健康对照者中的 32 名。在未接受 IgG 治疗的原发性抗体缺陷患者中，19 名无丙种球蛋白血症患者中的 17 名、24 名常见可变免疫缺陷患者中的 7 名和 14 名高 IgM 患者中的 5 名被原型正确识别，与参考检测方法的符合率为 67%。
快速 IgG 筛查（RIgGS）检测可以区分与无丙种球蛋白血症相关的低 IgG 水平和正常 IgG 抗体水平。由于 IgG 水平范围广泛以及高 IgM 的影响，区分 CVID 和高 IgM 具有挑战性。该检测方法可以促进原发性抗体缺陷患者的识别，并支持脊髓灰质炎监测计划。
