In a previously funded SFARI study of 100 children with autism spectrum disorder (ASD), Ruth O’Hara and her colleagues found that sleep-disordered breathing (SDB) — such as sleep apnea — occurs in more than 40 percent of children with ASD, a far higher rate than that seen in typically developing children. SDB is strongly linked to cognitive and behavioral deficits and elicits a systemic inflammatory response. Recent studies have focused on the role of microparticles (MPs) in SDB disorders. Cell-derived MPs are microvesicles of 0.05 to 1 micrometers, released through exocytic budding of the plasma membrane, following stimulation of different cell types.
Characterization of MPs provides a fine-grained and quantitative measure of cell-to-cell communication. Case-control and experimental studies indicate that platelet-, endothelium- and leukocyte-derived MP levels are increased in SDB and induce increased expression of proinflammatory molecules. Individuals with ASD are well documented to exhibit elevated levels of proinflammatory cytokines and chemokines compared with controls. Although MPs have not yet been examined in ASD, these alterations have all been associated with an abnormal production of MPs in proinflammatory disorders such as SDB. O’Hara and her team aim to assess whether proinflammatory processes in ASD are at least partially relayed through SDB-mediated MP.
Pilot data from O’Hara and her colleagues has shown increased numbers of endothelium MPs in children with ASD and SDB but not in children with ASD and no SDB, nor in typically developing children. However, due to their small size, detailed characterization of MPs has previously been hampered by limited detection techniques, such as flow cytometry. O’Hara’s team will utilize the latest developments in the field, nanoscale flow cytometry and nanoparticle tracking analysis, which allow analysis of particles smaller than 200 nanometers, outside the range of commonly used flow cytometry instruments. These approaches, already being implemented by the O’Hara team, will be used to examine whether MPs in individuals with ASD with SDB differ from those of individuals with ASD and no SDB, and from controls without SDB.