A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins
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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Elevated plasma cytokine levels (IL-1β, IL-6, IL-12p40, TNFα), altered immunoglobulin levels, elevated complement proteins, and increased chemokine levels (CCL2, CCL5, CCL11) are reported in the plasma of young children with autistic disorder compared with matched typically developing children.
“Elevated plasma cytokine levels (IL-1β, IL-6, IL-12p40 and TNFα) [82–84], altered immunoglobulin levels [85, 86], elevated levels of complement proteins [87], and increased chemokine levels (CCL2, CCL5 and CCL11) [88] are reported in the plasma of young children with AD compared with matched typically developing children.”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [87]
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- Authors
- Corbett, B. A., Kantor, A. B., Schulman, H., Walker, W. L., Lit, L., Ashwood, P., Rocke, D. M., & Sharp, F. R.
- Affiliations
- University of California Davis Medical Center (US)
- Pharmaceutical Product Development (United States) (US)
- University of California, Davis (US)
- Corresponding author
- Corbett, B A
- Venue
- Molecular Psychiatry
- Published
- 2006-12-26
- Volume
- 12
- Issue
- 3
- Pages
- 292-306
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2011080454
- Cited by
- 197
- References
- 97
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 7 · 2023: 13 · 2022: 8 · 2021: 18 · 2020: 11 · 2019: 13 · 2018: 6 · 2017: 13 · 2016: 4 · 2015: 12 · 2014: 18 · 2013: 14 · 2012: 14
- FWCI
- 2.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service (5K08NMHO72958)
- National Human Genome Research Institute (R01HG003352)
- National Institute of Neurological Disorders and Stroke (NS044283, R01NS043252, NS028167, P50NS044283, NS043252, R01NS028167)
- National Institute of Environmental Health Sciences (P42-ES-04699, P42ES004699)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- autism spectrum disorder, serum proteomics, apolipoproteins, apolipoprotein B-100, apolipoprotein A-IV, complement system, complement factor H-related proteins, C1q, FN1, differentially expressed proteins, children, high-functioning autism, peripheral blood biomarkers
- MeSH terms
- Apolipoproteins, Autistic Disorder, Child, Child, Preschool, Complement System Proteins, Female, Humans, Male, Mass Spectrometry, Gene Expression, Statistics, Nonparametric, Proteomics
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