PreDicta chip-based high resolution diagnosis of rhinovirus-induced wheeze

Katarzyna Niespodziana,Thomas Schlederer,Kamila Napora-Wijata,Nikolaos G Papadopoulos,Rudolf Valenta,Daniela Gallerano,Daniel Ebner,Phyllis C Vacal,Katarina Stenberg-Hammar,Clarissa R Cabauatan,Spyridon Megremis,Cilla Söderhäll,Christian Lupinek,Christian Harwanegg,Gunilla Hedlin,Marianne Van Hage

doi:10.1038/s41467-018-04591-0

Abstract

Rhinovirus (RV) infections are major triggers of acute exacerbations of severe respiratory diseases such as pre-school wheeze, asthma and chronic obstructive pulmonary disease (COPD). The occurrence of numerous RV types is a major challenge for the identification of the culprit virus types and for the improvement of virus type-specific treatment strategies. Here, we develop a chip containing 130 different micro-arrayed RV proteins and peptides and demonstrate in a cohort of 120 pre-school children, most of whom had been hospitalized due to acute wheeze, that it is possible to determine the culprit RV species with a minute blood sample by serology. Importantly, we identify RV-A and RV-C species as giving rise to most severe respiratory symptoms. Thus, we have generated a chip for the serological identification of RV-induced respiratory illness which should be useful for the rational development of preventive and therapeutic strategies targeting the most important RV types.

Highlights

Rhinovirus (RV) infections are major triggers of acute exacerbations of severe respiratory diseases such as pre-school wheeze, asthma and chronic obstructive pulmonary disease (COPD)
Within the European Union-funded project PreDicta we developed the PreDicta chip which is based on 130 micro-arrayed RV-derived proteins and peptides selected to represent the three RV species (RV-A, RV-B, and RV-C)
Using the PreDicta chip we could demonstrate in a cohort of 120 pre-school children with acute wheeze and a follow-up visit that the RV-specific antibody response (IgG > IgA) is directed against an N-terminal peptide of the major capsid protein VP1 which confirms earlier results obtained by the mapping of RV89-specific antibody responses[33]

Summary

Introduction

Rhinovirus (RV) infections are major triggers of acute exacerbations of severe respiratory diseases such as pre-school wheeze, asthma and chronic obstructive pulmonary disease (COPD). Respiratory viral infections are among the most common triggers of acute exacerbations of pre-school wheeze, asthma, and chronic obstructive pulmonary disease (COPD)[1,2,3]. The identification of the culprit rhinovirus species responsible for severe exacerbations of respiratory disease is an extremely important topic as certain RV species (e.g., RV-C) are suspected to be associated with more severe wheezing illnesses and acute asthma exacerbations in infants and children compared to others[18,19]. It is important to investigate the role of the different RV species for exacerbations of severe bronchial obstruction in different populations and for different age groups and manifestations of respiratory illness (e.g., pre-school wheeze, asthma, COPD, asthma-COPD overlap: ACO, CAP). The causal relationship of RV with CAP is unknown[27]

Methods

Results

Conclusion