This study examined the hypothesis that dysregulation of mucosal immune responses to respiratory infections is a critical event, which could be causal in respiratory arrest of some previously healthy infants. To examine this hypothesis, a prospective study was undertaken of infants presenting to the emergency department of a major teaching hospital with acute life threatening events (ALTE) of unknown cause and classified as "near-miss" SIDS. Salivary immunoglobulin concentrations were measured on admission and again after 14 days. The salivary immunoglobulins were compared with three control groups: infants with a mild upper respiratory tract infection (URTI); bronchiolitis; and healthy age-matched infants. The salivary IgA and IgM concentrations in the ALTE infants at presentation to hospital indicated a significant mucosal immune response had already occurred, with nearly 60% of the IgA concentrations significantly above the population-based reference ranges. The hyper-immune response was most evident in the ALTE infants with pathology evidence of an infection; 87% of these infants had salivary IgA concentrations on average 10 times higher that the age-related median concentration. The most prevalent pathogen identified in the ALTE infants was respiratory syncytial virus (RSV) (64%). RSV was also identified in all subjects with bronchiolitis. Risk factors for SIDS were assessed in each group. The data indicated that the ALTE infants diagnosed as 'near-miss' SIDS were a relatively homogeneous group, and most likely these ALTE infants and SIDS represent associated clinical outcomes. The study identified exposure to cigarette smoke and elevated salivary IgA concentrations as predictors of an ALTE. The study findings support the hypothesis of mucosal immune dysregulation in response to a respiratory infection in some infants with an ALTE. They provide a plausible explanation for certain SIDS risk factors. The underlying patho-physiological mechanism of proinflammatory responses to infections during a critical developmental period might be a critical factor in infants who have life-threatening apnoea or succumb to SIDS. The study raises the possibility of using salivary IgA to test infants who present with mild respiratory infections to identify a substantial number of infants at risk of developing an ALTE or SIDS, thus enabling intervention management to prevent such outcomes.
FEMS Immunology and Medical Microbiology Vol. 42, Issue 1, p. 105-118