Associations between Monocyte Cytokine Profiles and Co-Morbid Conditions in Autism Spectrum Disorders

Abstract

Autism spectrum disorder (ASD) is a behaviorally defined syndrome with frequent co-morbidities. Evidence indicate a role of innate immunity in ASD pathogenesis. This study addressed whether innate immune abnormalities are associated with ASD co-morbid conditions and/or other clinical co-variables when assessed as changes in monocyte cytokine profiles. This study included 109 ASD (median 11.5 year) and 26 non-ASD subjects (median 11.4 year). Monocyte cytokine profiles were evaluated in association with age/ethnicity, ASD severity, medications, and co-morbidities present in >15% of ASD subjects [gastrointestinal (GI) symptoms, epilepsy, allergic rhinitis, specific antibody deficiency (SAD), and fluctuating behavioral symptoms resembling pediatric acute-onset neuropsychiatric syndrome (PANS)]. ASD severity did not affect frequency of co-morbid conditions. GI symptoms, epilepsy, SAD, and PANS like symptoms revealed associations with changes in production of tumor necrosis factor-α (TNF-α)/soluble TNF-receptor II (sTNFRII), interleukin-1ß (IL-1ß)/IL-6/IL-10, and IL-6, respectively, mostly independent of other co-variables. ASD severity was associated with changes in multiple cytokines but frequently affected by other clinical co-variables. Our findings revealed associations between specific monocyte cytokine profiles and certain co-morbid conditions in ASD subjects, independent of other clinical co-variables. Our findings will aid in assessing treatment options for ASD co-morbidities and their effects on ASD behavioral symptoms.

Autism spectrum disorder and a possible role of anti-inflammatory treatments: experience in the pediatric allergy/immunology clinic

“…2) COX2 and ASD : In the previous studies that used peripheral blood monocytes from ASD subjects, as surrogates of microglial cells, increased production of the above-described cytokines in response to innate immune stimuli were observed ( 34 ). Such increases occur in ASD subjects that have a history of fluctuating behavioral symptoms and cognitive functioning following microbial infection ( 34 ). Interestingly, COX-2 and PGE2 were reported to be elevated in plasma of ASD subjects along with lower levels of α-synuclein ( 35 ).…”