A Novel Point-of-Care Rapid Diagnostic Test for Screening Individuals for Antibody Deficiencies

Shirli Israeli,Mohamed-Ridha Barbouche,Roger Peck,Melissa Atalig,Helen Storey,Afef Rais,Allison Golden,Najla Mekki

doi:10.1007/s10875-021-01179-0

Abstract

PurposeNo 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.MethodsThree 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.ResultsThe 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.ConclusionThe 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.

Highlights

Inborn errors of immunity known as primary immunodeficiency diseases (PIDs) are a heterogeneous group of more than 400 genetic disorders caused by mutations in genes involved in the development and/or the function of the immune system
With overall 67% agreement with the reference assay, the blue prototype could differentiate between low immunoglobulin G (IgG) levels associated with agammaglobulinemia and normal IgG antibody levels
Disagreement was highest with elevated IgM levels and higher IgG levels in common variable immunodeficiency (CVID), indicating that agreement was immunoglobulin concentration-dependent throughout all specimen types

Summary

Introduction

Inborn errors of immunity known as primary immunodeficiency diseases (PIDs) are a heterogeneous group of more than 400 genetic disorders caused by mutations in genes involved in the development and/or the function of the immune system. PID prevalence around the world ranges from 0.81 to 30.5 per 100,000 population [1]. The. Tunisia 3 University of Tunis El-Manar, Tunis, Tunisia higher prevalence is observed in populations characterized by a high rate of consanguinity [1, 2]. Primary antibody deficiencies (PADs) [3] are among the most common PIDs. Primary antibody deficiencies (PADs) [3] are among the most common PIDs They are characterized by an inability to generate sufficient antibody levels needed to induce a protective immune response. Patients with PAD are prone to recurrent bacterial infections in the respiratory and gastrointestinal tracts. They are at risk of contracting viral infections including with live viral vaccines

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