Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 23, Issue 1, Pages 124-133Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2008.08.001
Keywords
Autism spectrum disorder; Natural killer cells; Innate immunity; Cytotoxic proteins; Immunology; Genes
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Funding
- NIEHS Children's Center [2 P01 ES011269, R01ES015359]
- US EPA STAR [R833292, R829388]
- Cure Autism Now Foundation
- Peter Emch Foundation
- Ted Lindsey Foundation
- UC Davis M.I.N.D. Institute
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P01ES011269, R01ES015359] Funding Source: NIH RePORTER
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Immune related abnormalities have repeatedly been reported in autism spectrum disorders (ASD), including evidence of immune dysregulation and autoimmune phenomena. NK cells may play an important role in neurodevelopmental disorders such as ASD. Here we performed a gene expression screen and cellular functional analysis on peripheral blood obtained from 52 children with ASD and 27 typically developing control children enrolled in the case-control CHARGE study. RNA expression of NK cell receptors and effector molecules were significantly upregulated in ASD. Flow cytometric analysis of NK cells demonstrated increased production of perforin, granzyme B, and interferon gamma (IFN gamma) under resting conditions in children with ASD (p < 0.01). Following NK cell stimulation in the presence of K562 target cells, the cytotoxicity of NK cells was significantly reduced in ASD compared with controls (p < 0.02). Furthermore, under similar stimulation conditions the presence of perforin, granzyme B, and IFN gamma in NK cells from ASD children was significantly lower compared with controls (p<0.001). These findings suggest possible dysfunction of NK cells in children with ASD. Abnormalities in NK cells may represent a susceptibility factor in ASD and may predispose to the development of autoimmunity and/or adverse neuroimmune interactions during critical periods of development. (c) 2008 Elsevier Inc. All rights reserved.
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