Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome

Abstract

Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication deficits, and restricted repetitive interests and behaviors. A potential role for immune dysfunction has been suggested in ASD. To test this hypothesis, we investigated evidence of differential cytokine release in plasma samples obtained from 2-5 year-old children with ASD compared with age-matched typically developing (TD) children and children with developmental disabilities other than autism (DD). Participants were recruited as part of the population based case-control CHARGE (Childhood Autism Risks from Genetics and Environment) study and included: 97 participants with a confirmed diagnosis of ASD using standard assessments (DSM IV criteria and ADOS, ADI-R), 87 confirmed TD controls, and 39 confirmed DD controls. Plasma was isolated and cytokine production was assessed by multiplex Luminex™ analysis. Observations indicate significant increases in plasma levels of a number of cytokines, including IL-1β, IL-6, IL-8 and IL-12p40 in the ASD group compared with TD controls (p < 0.04). Moreover, when the ASD group was separated based on the onset of symptoms, it was noted that the increased cytokine levels were predominantly in ASD children who had a regressive form of ASD. In addition, increasing cytokine levels were associated with more impaired communication and aberrant behaviors. In conclusion, using larger number of participants than previous studies, we report significantly shifted cytokine profiles in ASD. These findings suggest that ongoing inflammatory responses may be linked to disturbances in behavior and require confirmation in larger replication studies. The characterization of immunological parameters in ASD has important implications for diagnosis, and should be considered when designing therapeutic strategies to treat core symptoms and behavioral impairments of ASD.

The Role of the Immune System in Autism Spectrum Disorder

“…Examining children from the same cohort, the authors also published on increased levels of the chemokines MCP-1, RANTES, and eotaxin (Ashwood et al, 2011c). In both studies, increased cytokine or chemokine levels were correlated with increased aberrant behavior and impaired development (Ashwood et al, 2011a(Ashwood et al, , 2011c. A related study by the same team supported these findings using PHAstimulated PBMCs, and correlated a Th1-like response with greater impairments and behavior aberrancies and a Th2-like response to better cognitive and adaptive function (Ashwood et al, 2011b).…”

“…A large 2011 study of children with ASD found an increase in plasma levels of a broad range of cytokines, including the Th1-like IL-12p40 and pro-inflammatory cytokines IL-1β, IL-6, IL-8, and GM-CSF (Ashwood et al, 2011a). Examining children from the same cohort, the authors also published on increased levels of the chemokines MCP-1, RANTES, and eotaxin (Ashwood et al, 2011c).…”

Vitamin D deficiency and autism; a review on recent findings

“…Low levels of vitamin D during fetal and neonatal development could be as a result of poor TPH2 expression and consequently diminish serotonin concentrations in the developing brain (47). Strengthened values of inflammatory cytokines are observed in individuals with autism (48). Inflammatory cytokines such as CRP, IL-10 and IL-6 are boosted in people with vitamin D inadequacy (49).…”

“…This hormone presents immunomodulation, neuroprotection and antiepileptic properties (47). Prenatal, postnatal and even and neonatal vitamin D supplementation is imperative for ordinary brain activities (47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60). The noticeable rise in the frequency of autism across the last 20 years is due to an increase in medical cautions to avoid the sun exposure because of its increasing of skin cancers.…”

Clinical and laboratory diagnosis of autism spectrum disorders in children

“…В крови пациентов выявлены различные маркеры воспале-ния: повышенный уровень провоспалительных ци-токинов [7,8], белков острой фазы воспаления [9]; изменение активности протеолитических фермен-тов, ответственных за сосудистую проницаемость [3,6], а также повышенный уровень аутоантител к нейроантигенам [6,11,13]. Признаки нейро-воспалительных реакций -активация микрогли-альных клеток, увеличенная экспрессия провос-палительных цитокинов, нарушения микрососуди-стого русла -наблюдаются также в мозге пациен-тов [17,20].…”