32403
Systematic Profiling of Viral Antibodies in Children with Autism Spectrum Disorder (ASD)
Animal studies suggest that maternal viral exposure results in immune activation altering the activity of multiple genes/associated pathways in the developing fetal brain. Importantly, many of these genes are key to developmental processes that occur before birth, demonstrating how maternal viral exposure could increase the risk of having a child with ASD. Similarly, post-natal viral exposures, particularly those that cause respiratory tract infections (RTIs), may also be an ASD risk factor.
Objectives:
The aim of this study was to use VirScan to perform a systematic analysis of viral antibodies in sera from boys (2-9 years) with and without ASD to examine their post-natal viral exposure histories.
Methods:
Subjects included 100 boys with ASD (mean age 5.92, SD 1.95 years) and 100 typically developing (TD) boys as controls (mean age 5.99, SD 2.17 years). An ASD diagnosis was confirmed using the ADOS and ADI-R. Analysis of viral antibodies in serum samples was performed using VirScan, which combines DNA synthesis and bacteriophage display and allows for the systematic detection of over 200 viruses from more than 20 different virus families. Data were analyzed using Fisher, t, and Wilcoxon rank tests.
Results:
VirScan detected antibodies that interacted with peptides from 266/499 (53.3%) viruses. Viral peptide hits reported for children both with and without ASD are shown in Table 1. Not surprisingly, 100% ASD and 99% control subjects had antibodies to rhinovirus, the common cold. There were also high frequencies of viruses that cause various gastrointestinal and RTIs such as adenoviruses, herpesviruses, RSV and enteroviruses. There were no significant differences between ASD and controls for any viral antibodies detected after adjusting for multiple hypothesis testing. Interestingly, very low numbers of viral peptides to hepatitis B, measles, mumps, rubella, and rotavirus (from either the vaccine or viral infection) were detected. This could be due to the original immune response being low, the antibody response to these vaccines waning over time, a depletion of long-lived memory B cells, or that VirScan cannot accurately capture this data. Further analysis of the effects of age on viral exposures in ASD is underway.
Table 1: Summary of the some of the most commonly detected antibodies in children with and without ASD. Data represents the percentage of subjects with antibodies detected against at least one peptide from each virus.
Virus species |
Control % |
ASD % |
Rhinovirus_A |
100.0 |
99.02 |
Human adenovirus_C |
90.20 |
71.57 |
Human respiratory syncytial virus |
88.24 |
87.25 |
Human herpesvirus-6B |
75.49 |
73.53 |
Enterovirus_B |
63.73 |
61.76 |
Human herpes virus-5 |
52.94 |
49.02 |
Enterovirus_A |
50.98 |
51.96 |
Variola virus |
50.00 |
32.35 |
Norwalk virus |
49.02 |
53.92 |
Human herpesvirus-4 |
42.16 |
38.24 |
Enterovirus_C |
29.41 |
33.33 |
Human adenovirus_B |
27.45 |
14.71 |
Human influenza virus-3 |
21.57 |
16.67 |
Human herpes virus-7 |
21.57 |
22.55 |
Influenza A virus |
20.59 |
14.71 |
Rotavirus_A |
12.75 |
7.84 |
Conclusions:
These data suggest that VirScan may be useful in examining viral histories of children with ASD. Future studies should focus on comparing prenatal maternal samples with those of the newborn to further elucidate putative prenatal viral causes of ASD, as well as performing viral surveillance throughout post-natal development.