A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

• Published in: Molecular psychiatry Vol. 12; no. 3; pp. 292 - 306
• Main Authors: CORBETT, B. A, KANTOR, A. B, SCHULMAN, H, WALKER, W. L, LIT, L, ASHWOOD, P, ROCKE, D. M, SHARP, F. R
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.03.2007
• Subjects: Apolipoproteins; Apolipoproteins - blood; Apoptosis; Autism; Autistic children; Autistic Disorder - blood; Biological and medical sciences; Child; Child clinical studies; Child, Preschool; Children; Cholesterol; Complement component C1q; Complement factor H; Complement system; Complement System Proteins - metabolism; Developmental disorders; Female; Fibronectin; Gene Expression - physiology; Humans; Infantile autism; Lipids; Liquid chromatography; Lysis; Male; Mass Spectrometry - methods; Mass spectroscopy; Medical sciences; Peptides; Peripheral blood; Proteins; Proteomics; Proteomics - methods; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Serum proteins; Statistics, Nonparametric; Trypsin; Vitamin E; Human; Autism; apolipoprotein B-100; Proteomics; Developmental disorder; Apolipoprotein; complement; Child; blood; Protein
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/sj.mp.4001943

Modern methods that use systematic, quantitative and unbiased approaches are making it possible to discover proteins altered by a disease. To identify proteins that might be differentially expressed in autism, serum proteins from blood were subjected to trypsin digestion followed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) on time-of-flight (TOF) instruments to identify differentially expressed peptides. Children with autism 4-6 years of age (n=69) were compared to typically developing children (n=35) with similar age and gender distributions. A total of 6348 peptide components were quantified. Of these, five peptide components corresponding to four known proteins had an effect size >0.99 with a P<0.05 and a Mascot identification score of 30 or greater for autism compared to controls. The four proteins were: Apolipoprotein (apo) B-100, Complement Factor H Related Protein (FHR1), Complement C1q and Fibronectin 1 (FN1). In addition, apo B-100 and apo A-IV were higher in children with high compared to low functioning autism. Apos are involved in the transport of lipids, cholesterol and vitamin E. The complement system is involved in the lysis and removal of infectious organisms in blood, and may be involved in cellular apoptosis in brain. Despite limitations of the study, including the low fold changes and variable detection rates for the peptide components, the data support possible differences of circulating proteins in autism, and should help stimulate the continued search for causes and treatments of autism by examining peripheral blood.