Serum immunoglobulin A as a biomarker for respiratory syncytial virus infection in children aged <2 years.

Abstract

Aims: Past research suggested respiratory syncytial virus (RSV) specific serum immunoglobulin A (IgA) antibodies as a biomarker of previous RSV infections in young infants accounting for maternal immunity. This study aimed to confirm this association and to establish a serological threshold for discriminating RSV-naïve infants from those who have experienced RSV.

Material and methods: This study involves 135 infants from the LoewenKIDS study with nasal swabs collected at each acute respiratory infection, and serum samples collected at ages 1 and 2 years. RSV presence in swabs was ascertained by reverse transcriptase PCR; RSV-specific IgG and IgA antibody levels against five different structural proteins and RSV neutralising antibodies were measured in sera. Robust Mixture Discriminant Analysis was used to determine the cut-off values and account for false negatives.

Results: Of 135 included infants, 131 had available data at year 1 (Y1) and 95 at year 2 (Y2). Pre-F IgA concentrations were higher in infants with PCR-confirmed RSV infections. There was a further increase in IgA, IgG and neutralising antibody titre concentrations from Y1 to Y2 consistent with re-infections. Based on robust mixture discriminant analysis, the cut-off values of pre-F IgA level indicative of past RSV infection were 0.23 AU·mL^-1 at Y1 and 0.22 AU·mL^-1 at Y2.

Conclusion: This study shows that in children aged <2 years, a previous RSV infection is accompanied by serum pre-F IgA antibody levels above 0.22 AU·mL^-1, a value close to a previously proposed cut-off (0.19 AU·mL^-1) based on seroresponse data only. The confirmed threshold can be of use in studies assessing vaccination strategies.