Respiratory syncytial virus-specific immunoglobulin G (IgG) concentrations associate with environmental and genetic factors: the Factors Influencing Pediatric Asthma Study.

Exposure to respiratory syncytial virus (RSV) during childhood is nearly ubiquitous by age two, and infants who develop severe RSV bronchiolitis are more likely to develop asthma later in life. In the Factors Influencing Pediatric Asthma (FIPA) study including 319 children from a Northern Plains American Indian community, we found 73% of children to have high concentrations of RSV-specific IgG (>40 IU/mL). High concentration of RSV-specific IgG was associated with increased exposure to second-hand tobacco smoke (p=7.5x10-4), larger household size (p=4.0x10-3), and lower levels of total serum IgE (p=5.1x10-3). Parents of children with asthma more often reported an RSV diagnosis and/or hospitalization due to RSV, and children with asthma had lower concentrations of RSV IgG as compared to those without asthma among RSV-exposed individuals (mean 117 IU/mL vs. 154, p=7.1x10-4). However, lower RSV IgG was surprisingly exclusive to children with asthma recruited during the winter months when RSV is thought to circulate more broadly. Multivariate regression indicated the strongest predictors of RSV-specific IgG concentration included asthma status (p=0.040), per cent eosinophils (p=0.035), and an asthma x RSV season interaction (p=3.7x10-3). Among candidate genes, we identified a genetic association between an intronic variant in IFNL4 and RSV-specific IgG concentration whereby the minor allele (A) was associated with higher concentration (rs12979860, p=4.3x10-3). Overall our findings suggest there are seasonal differences in immunological response to RSV infection in asthma cases vs. controls, and identify both environmental and genetic contributions that warrant further investigation.