Altered gene expression and function of peripheral blood natural killer cells in

[Guest guest]

Altered gene expression and function of peripheral blood natural

killer cells in children with autism

Brain Behav Immun. 2009 Jan;23(1):124-33.

Enstrom AM, Lit L, Onore CE, Gregg JP, Hansen RL, Pessah IN, Hertz-

Picciotto I,Van de Water JA, Sharp FR, Ashwood P.

Department of Medical Microbiology and Immunology, University of

California at , USA.

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

functionalanalysis 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.

PMID: 18762240 [PubMed - in process]