Detection of Circulating VZV-Glycoprotein E-Specific Antibodies by Chemiluminescent Immunoassay (CLIA) for Varicella-Zoster Diagnosis.

Tengchuan Jin,Siping Zhang,Chen Feng,Yiyu Deng,Huan Ma,Ayesha Zahid,Ahmed Mohammed,Guangtao Xu,Zhao Dan,Fleury Augustin Nsole Biteghe,Weihong Zeng,Arnaud John Kombe Kombe,Jiajia Xie,Keyuan Zhu,Ruixue Chang,Yunru Yang

doi:10.3390/pathogens11010066

Abstract

Varicella and herpes zoster are mild symptoms-associated diseases caused by varicella–zoster virus (VZV). They often cause severe complications (disseminated zoster), leading to death when diagnoses and treatment are delayed. However, most commercial VZV diagnostic tests have low sensitivity, and the most sensitive tests are unevenly available worldwide. Here, we developed and validated a highly sensitive VZV diagnostic kit based on the chemiluminescent immunoassay (CLIA) approach. VZV-glycoprotein E (gE) was used to develop a CLIA diagnostic approach for detecting VZV-specific IgA, IgG, and IgM. The kit was tested with 62 blood samples from 29 VZV-patients classified by standard ELISA into true-positive and equivocal groups and 453 blood samples from VZV-negative individuals. The diagnostic accuracy of the CLIA kit was evaluated by receiver-operating characteristic (ROC) analysis. The relationships of immunoglobulin-isotype levels between the two groups and with patient age ranges were analyzed. Overall, the developed CLIA-based diagnostic kit demonstrated the detection of VZV-specific immunoglobulin titers depending on sample dilution. From the ELISA-based true-positive patient samples, the diagnostic approach showed sensitivities of 95.2%, 95.2%, and 97.6% and specificities of 98.0%, 100%, and 98.9% for the detection of VZV-gE-specific IgA, IgG, and IgM, respectively. Combining IgM to IgG and IgA detection improved diagnostic accuracy. Comparative analyses on diagnosing patients with equivocal results displaying very low immunoglobulin titers revealed that the CLIA-based diagnostic approach is overall more sensitive than ELISA. In the presence of typical VZV symptoms, CLIA-based detection of high titer of IgM and low titer of IgA/IgG suggested the equivocal patients experienced primary VZV infection. Furthermore, while no difference in IgA/IgG level was found regarding patient age, IgM level was significantly higher in young adults. The CLIA approach-based detection kit for diagnosing VZV-gE-specific IgA, IgG, and IgM is simple, suitable for high-throughput routine analysis situations, and provides enhanced specificity compared to ELISA.

Highlights

Varicella–zoster virus (VZV), known as human herpesvirus-3 (HHV-3), belongs to the α-herpesviridae subfamily [1]
29 people (Supplementary Figure S1) with an average age of 52 (20 to 82 years old) were enrolled and retained as varicella–zoster virus (VZV)-infected patients, which was based on typical VZV symptoms and using ELISA tests
We aimed to determine the diagnostic performance of the chemiluminescent immunoassay (CLIA)-based IgA, IgG, and IgM detection kit in diagnosing VZV infection in a random population

Summary

Introduction

Varicella–zoster virus (VZV), known as human herpesvirus-3 (HHV-3), belongs to the α-herpesviridae subfamily [1]. It is responsible for varicella disease or chickenpox in children, adolescents, and young adults. The most life-threatening complications include mental development deficit, meningoencephalitis, and post-infectious encephalopathy, in varicella cases. Complications include vasculitis, zoster sine herpete, and post-herpetic neuralgia. A lack of early diagnosis results in treatment delays, which usually leads to fatalities, especially in newborns, elders, organ transplant recipients, and immunocompromised people experiencing disseminated herpes zoster [3,4,5,6,7,8]

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