Evaluation of an IgG deficiency rapid screening test among Pakistani children with primary immunodeficiency (PID)

Primary Immunodeficiency Diseases (PIDs) are rare, inherited inborn errors of immunity characterized by immune dysregulation and low immune protection often characterized by low immunoglobulin levels. If antibody deficiencies due to PID are present and Sabin OPV (oral poliovirus vaccine) is encountered it can lead to rare persistent immunodeficiency-related vaccine-derived poliovirus (iVDPV) infections due to an inability to clear OPV. Most PIDs associated with viral shedding manifest with low antibody levels, therefore, it is hypothesized that low immunoglobulin G (IgG) may be a screening biomarker for PIDs. Methods: In this article, we describe a case-controlled, diagnostic accuracy investigation aimed to determine the performance of a semi-quantitative rapid screening test (IgG Total Test) to differentiate between very low, moderately low, and normal IgG levels associated with pediatric PID status. Ninety-eight capillary whole blood and ninety-seven matched serum samples were collected from patients and run using the IgG Total Test. We evaluated the percentage agreement between IgG Total Test results with capillary blood or serum and the laboratory reference IgG values, and evaluated usability, acceptability, and feasibility for integrating the IgG Total Test into tertiary hospitals in Pakistan. Results: A low number of samples had reference IgG values that would be categorized as moderately low (4) or very low IgG levels (1). Amongst normal IgG levels, capillary samples produced lower specificity (52%) compared to serum samples (96%). Both capillary and serum results detected the single very low IgG sample. The usability, acceptability and feasibility scored highly. Conclusions: A serum-based rapid test was capable of differentiating normal and very low IgG, but had lower specificity with capillary sample use. Low numbers of very low IgG prevented robust analysis of performance of the rapid IgG screening test. Further development could improve a rapid IgG level assessment for PID screening, alongside Jeffrey Modell warning signs, to enhance patient care and support additional use cases related to intravenous immunoglobulin administration.