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

Molecular Psychiatry volume 12, pages 292–306 (2007)Cite this article

Abstract

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.

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Acknowledgements

We thank David G Amaral for the initial inspiration of this investigation. We are grateful to the many individuals at the MIND Institute especially Meridith Brandt, Anny Wu, Susan Bacalman, Veronica Lopez-Villasenor, Nuny Khamphay and many others that helped make the study possible. We are grateful to the individuals at PPD who contributed to sample processing and analysis, especially Hua Lin and Markus Anderle. Most importantly, we are indebted to the children and families who participated in this study. This study was supported by a grant from the MIND Institute, NIH grants to Frank R Sharp (NS043252; NS028167; and NS044283), David Rocke (P42-ES04699 and R01-HG003352) and by an NIH career development award to Blythe A Corbett (5K08NMHO72958).

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, University of California at Davis, Sacramento, CA, USA

    B A Corbett

  2. Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California at Davis, Sacramento, CA, USA

    B A Corbett, W L Walker, L Lit, P Ashwood & F R Sharp

  3. PPD Biomarker Discovery Sciences, Menlo Park, CA, USA

    A B Kantor & H Schulman

  4. Department of Neurology, University of California at Davis, Sacramento, CA, USA

    W L Walker, L Lit & F R Sharp

  5. Department of Medical Microbiology and Immunology, University of California at Davis, Sacramento, CA, USA

    P Ashwood

  6. Department of Public Health Sciences, Division of Biostatistics, University of California at Davis, Sacramento, CA, USA

    D M Rocke

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Corbett, B., Kantor, A., Schulman, H. et al. A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins. Mol Psychiatry 12, 292–306 (2007). https://doi.org/10.1038/sj.mp.4001943

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