Children with autism spectrum disorders (ASD) who exhibit chronic gastrointestinal (GI) symptoms and marked fluctuation of behavioral symptoms exhibit distinct innate immune abnormalities and transcriptional profiles of peripheral blood (PB) monocytes
Harumi Jyonouchia, Lee Genga, Deanna L. Streckb and Gokce A. Torunerb
Division of Allergy/Immunology and Infection Diseases, Department of Pediatrics, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School (NJMS), 185 South Orange Ave, Newark, NJ, United States
Institute of Genomic Medicine, Department of Pediatrics, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School (NJMS), 185 South Orange Ave, Newark, NJ, United States
Received 16 February 2011; revised 26 June 2011; accepted 6 July 2011. Available online 30 July 2011.
Innate/adaptive immune responses and transcript profiles of peripheral blood monocytes were studied in ASD children who exhibit fluctuating behavioral symptoms following infection and other immune insults (ASD/Inf, N = 30). The ASD/Inf children with persistent gastrointestinal symptoms (ASD/Inf + GI, N = 19), revealed less production of proinflammatory and counter-regulatory cytokines with stimuli of innate immunity and marked changes in transcript profiles of monocytes as compared to ASD/no-Inf (N = 28) and normal (N = 26) controls. This included a 4–5 fold up-regulation of chemokines (CCL2 and CCL7), consistent with the production of more CCL2 by ASD/Inf + GI cells. These results indicate dysregulated innate immune defense in the ASD/Inf + GI children, rendering them more vulnerable to common microbial infection/dysbiosis and possibly subsequent behavioral changes.
August 8, 2011
August 1, 2011
Ancestry of pink disease (infantile acrodynia) identified as a risk factor for autism spectrum disorders.
J Toxicol Environ Health A. 2011 Sep 15;74(18):1185-94. Shandley K, Austin DW.
Swinburne Autism Bio-Research Initiative (SABRI), Brain and Psychological Sciences Research Centre , Swinburne University of Technology , Hawthorn , Victoria , Australia.
Pink disease (infantile acrodynia) was especially prevalent in the first half of the 20th century. Primarily attributed to exposure to mercury (Hg) commonly found in teething powders, the condition was developed by approximately 1 in 500 exposed children. The differential risk factor was identified as an idiosyncratic sensitivity to Hg. Autismspectrum disorders (ASD) have also been postulated to be produced by Hg. Analogous to the pink disease experience, Hg exposure is widespread yet only a fraction of exposed children develop an ASD, suggesting sensitivity to Hg may also be present in children with an ASD. The objective of this study was to test the hypothesis that individuals with a known hypersensitivity to Hg (pink disease survivors) may be more likely to have descendants with an ASD. Five hundred and twenty-two participants who had previously been diagnosed with pink disease completed a survey on the health outcomes of their descendants. The prevalence rates of ASD and a variety of other clinical conditions diagnosed in childhood (attention deficit hyperactivity disorder, epilepsy, Fragile X syndrome, and Down syndrome) were compared to well-established general population prevalence rates. The results showed the prevalence rate of ASD among the grandchildren of pink disease survivors (1 in 22) to be significantly higher than the comparable general population prevalence rate (1 in 160). The results support the hypothesis that Hg sensitivity may be a heritable/genetic risk factor for ASD.