Cytokine profiles by peripheral blood monocytes are associated with changes in behavioral symptoms following immune insults in a subset of ASD subjects: an inflammatory subtype?

Harumi Jyonouchi, Lee Geng, Amy L Davidow

BackgroundSome children with autism spectrum disorders (ASD) are characterized by fluctuating behavioral symptoms following immune insults, persistent gastrointestinal (GI) symptoms, and a lack of response to the first-line intervention measures. These children have been categorized as the ASD-inflammatory subtype (ASD-IS) for this study. We reported a high prevalence of non-IgE mediated food allergy (NFA) in young ASD children before, but not all ASD/NFA children reveal such clinical features of ASD-IS. This study addressed whether behavioral changes of ASD-IS are associated with innate immune abnormalities manifested in isolated peripheral blood (PB) monocytes (Mo), major innate immune cells in the PB.MethodsThis study includes three groups of ASD subjects (ASD-IS subjects (N =24), ASD controls with a history of NFA (ASD/NFA (N =20), and ASD/non-NFA controls (N =20)) and three groups of non-ASD controls (non-ASD/NFA subjects (N =16), those diagnosed with pediatric acute onset-neuropsychiatric syndrome (PANS, N =18), and normal controls without NFA or PANS (N =16)). Functions of purified PB Mo were assessed by measuring the production of inflammatory and counter-regulatory cytokines with or without stimuli of innate immunity (lipopolysaccharide (LPS), zymosan, CL097, and candida heat extracts as a source of ß-lactam). In ASD-IS and PANS subjects, these assays were done in the state of behavioral exacerbation (`flare¿) and in the stable (`non-flare¿) condition. ASD-IS children in the `flare¿ state revealed worsening irritability, lethargy and hyperactivity.Results`Flare¿ ASD-IS PB Mo produced higher amounts of inflammatory cytokines (IL-1ß and IL-6) without stimuli than `non-flare¿ ASD-IS cells. With zymosan, `flare¿ ASD-IS cells produced more IL-1ß than most control cells, despite spontaneous production of large amounts of IL-1ß. Moreover, `flare¿ ASD-IS Mo produced less IL-10, a counterregulatory cytokine, in response to stimuli than `non-flare¿ cells or other control cells. These changes were not observed in PANS cells.ConclusionsWe observed an imbalance in the production of inflammatory (IL-1ß and IL-6) and counterregulatory (IL-10) cytokines by `flare¿ ASD-IS monocytes, which may indicate an association between intrinsic abnormalities of PB Mo and changes in behavioral symptoms in the ASD-IS subjects.