TY - JOUR
T1 - Altered gene expression and function of peripheral blood natural killer cells in children with autism
AU - Enstrom, Amanda M.
AU - Lit, Lisa
AU - Onore, Charity E.
AU - Gregg, Jeffrey
AU - Hansen, Robin L
AU - Pessah, Isaac N
AU - Hertz-Picciotto, Irva
AU - Van de Water, Judith A
AU - Sharp, Frank R
AU - Ashwood, Paul
PY - 2009/1
Y1 - 2009/1
N2 - 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 (IFNγ) 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 IFNγ 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.
AB - 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 (IFNγ) 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 IFNγ 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.
KW - Autism spectrum disorder
KW - Cytotoxic proteins
KW - Genes
KW - Immunology
KW - Innate immunity
KW - Natural killer cells
UR - http://www.scopus.com/inward/record.url?scp=56949100252&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=56949100252&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2008.08.001
DO - 10.1016/j.bbi.2008.08.001
M3 - Article
C2 - 18762240
AN - SCOPUS:56949100252
VL - 23
SP - 124
EP - 133
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
SN - 0889-1591
IS - 1
ER -