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.

The Potential for Proteomics in Understanding Neurodevelopmental Disorders

“…Indeed, preliminary putative biomarkers have been identified in human blood sera taken from people with ASDs. For example, alterations in complement proteins [40][41][42] as well as in apolipoproteins, may be present [13,38,40]. Corbett et al [40] found that five peptide components corresponding to four known proteins (Apolipoprotein (apo) B100, Complement Factor H Related Protein (FHR1), Complement C1q and Fibronectin 1 (FN1)) had a MASCOT score of 30 or greater for autism compared to controls.…”

“…As stated earlier in this manuscript, preliminary putative biomarkers have been identified in blood and saliva taken from individuals from other neurodevelopmental disorders, for example, idiopathic ASD. To give one example of putative biomarker identification, in human blood sera taken from people with ASDs, alterations in complement proteins [40][41][42] as well as in apolipoproteins, may be present [5,40]. Proteomic analysis of SLOS biomarkers has the potential to reveal new information about the disorder.…”

The Promise of Multi-Omics and Clinical Data Integration to Identify and Target Personalized Healthcare Approaches in Autism Spectrum Disorders

“…Studies have found increased levels of proteins involved in synapse formation, such as brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) in ASD samples (Chauhan et al, 2011;Correia et al, 2010;Fatemi et al, 2002;Riikonen, 2003;Schwarz et al, 2011;Thanseem et al, 2012). Proteomic analyses have also found altered levels of immune system-regulating proteins, such as apolipoprotein in the cerebrospinal fluid and blood of individuals with ASD compared to controls (Corbett et al, 2007;Molloy et al, 2006;Woods et al, 2012;Zimmerman et al, 2005). Proteins show great promise as useful biomarkers for ASD, but large-scale replications are needed.…”

From Child-Robot Interaction to Child-Robot-Therapist Interaction: A Case Study in Autism

“…The ToM deficit is associated with processing of non-verbal sounds [10], human voices [8], touching [21], eye contact [17] and facial information [1,6]. Individuals with autism often exhibit impaired processing of emotions [14] mani-fested in the form of increased stress and anxiety [5,15]. As a result, children with autism regularly engage in stereotyped ritualistic behaviours and have difficulties initiating activities to share interests and cooperate with others.…”