International Meeting for Autism Research (London, May 15-17, 2008): Autism Subgroup BioMarkers: RNA Expression Studies

Thursday, May 15, 2008

Champagne Terrace/Bordeaux (Novotel London West)

9:30 AM

L. Lit , Neurology and Genetics, Sacramento

S. Ozonoff , Psychiatry and Behavioral Sciences, M.I.N.D. Institute, University of California at Davis Medical Center, Sacramento, CA

I. Hertz-Picciotto , Public Health Sciences, University of California at Davis, Sacramento

J. Van de Water , Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA

R. L. Hansen , Department of Pediatrics and the M.I.N.D. Institute, University of California, Davis, Sacramento, CA

P. Ashwood , Department of Medical Microbiology and Immunology, and the M.I.N.D. Institute, University of California at Davis, Sacramento, CA

J. P. Gregg , Pathology, University of California at Davis, Sacramento

R. R. Davis , Pathology, University of California at Davis, Sacramento

A. Enstrom , Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Sacramento

I. N. Pessah , Veterinary Molecular Biosciences, University of California at Davis, Sacramento

F. R. Sharp , Neurology, Sacramento, CA

Background: Many phenotypes are being described for children with autism, including onset type. Comparison of children with autism (AU) and pervasive developmental disorders not otherwise specified (PDDNOS) to GP yielded 12 genes expressed in Natural Killer (NK) cells or CD8+ cytotoxic lymphocytes. Approximately 70% of AU subjects had high expression of these NK/CD8+ genes.

Objectives: Identify RNA expression biomarkers associated with AU subgroups.

Methods: 35 children ages 2-5 with autism (AU) and 14 PDDNOS children were compared to 12 typically developing children (GP). Total RNA from blood was processed on human Affymetrix microarrays.

Results: Using the 12 genes expressed in NK cells, AU children were separated into high NK and normal NK expression. Comparison of AU children with high NK to normal NK yielded hundreds of genes. Unsupervised cluster analyses revealed 3-4 subgroups. Of 10 children with early onset AU, 9 had high NK gene expression profiles. Specific comparisons of AU subjects with early onset, regression, mixed onset, and plateau clinical onset phenotypes demonstrated specific gene expression profiles for each clinically defined onset pattern of autism.

Conclusions: These studies support immune profiles associated with clinical onset definition in some children with autism. They show that a substantial proportion of children with autism – though not all – have abnormal expression of genes associated with NK/CD8+ cells. There are distinct patterns of RNA expression that are associated with at least two and perhaps as many as four types of onset of autism. The data support differences in peripheral blood RNA expression in 50-70% of children with autism compared with GP. Those children without these changes may have abnormalities confined to brain, and therefore have no observable changes in peripheral blood. Alternatively, they might have mothers with peripheral immune abnormalities that might secondarily affect the developing fetal brain with an appropriate environmental trigger.

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