Altered gene expression and function of peripheral blood natural killer cells in children with autism.
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 (IFNgamma) 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 IFNgamma 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.
Enstrom
Amanda M
AM
Department of Medical Microbiology and Immunology, University of California at Davis, USA.
Lit
Lisa
L
Onore
Charity E
CE
Gregg
Jeff P
JP
Hansen
Robin L
RL
Pessah
Isaac N
IN
Hertz-Picciotto
Irva
I
Van de Water
Judy A
JA
Sharp
Frank R
FR
Ashwood
Paul
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