Reduced levels of immunoglobulin in children with autism correlates with behavioral symptoms
Open accessAbstract
Objectives: To assay if plasma antibody levels in children with autism or developmental delays (DD) differ from those with typical development as an indicator of immune function and to correlate antibody levels with severity of behavioral symptoms. Methods: Plasma was collected from children with autistic disorder (AU; n=116), DD but not autism (n=32), autism spectrum disorder but not full autism (n=27), and age‐matched typically developing (TD) controls (n=96). Samples were assayed for systemic levels of immunoglobulin (IgG, IgM, IgA, and IgE) by enzyme‐linked immunosorbent assay. Subjects with autism were evaluated using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview—Revised, and all subjects were scored on the Aberrant Behavior Checklist (ABC) by the parents. Numerical scores for each of the ABC subscales as well as the total scores were then correlated with Ig levels. Results: Children with AU have a significantly reduced level of plasma IgG (5.39±0.29 mg/mL) compared to the TD (7.72±0.28 mg/mL; P<0.001) and DD children (8.23±0.49 mg/mL; P<0.001). Children with autism also had a reduced level of plasma IgM (0.670.06mg/mL) compared to TD (0.79±0.05 mg/mL; P<0.05). Ig levels were negatively correlated with ABC scores for all children (IgG: r=−0.334, P<0.0001; IgM: r=−0.167, P=0.0285). Conclusion: Children with AU have significantly reduced levels of plasma IgG and IgM compared to both DD and TD controls, suggesting an underlying defect in immune function. This reduction in specific Ig levels correlates with behavioral severity, where those patients with the highest scores in the behavioral battery have the most reduced levels of IgG and IgM.
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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 [85]
Age of the children is most likely a contributing factor to discrepancies in IgG levels, with IgG levels changing significantly and rapidly through the first decade of life.
“age of the children is most likely a contributing factor, with IgG levels changing significantly and rapidly through the first decade of life (Heuer et al, 2008).”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Heuer et al, 2008
A 2008 study of over 250 children found a reduction of plasma IgG and IgM levels in young children with autism, with IgG levels negatively correlated with ABC scores regardless of ASD status.
“a 2008 study of over 250 children found a reduction of plasma IgG and IgM levels circulating in young children with autism, in particular IgG, the levels of which correlated negatively with scores on the ABC, regardless of ASD status (Heuer et al, 2008).”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Heuer et al, 2008
The negative relationships between TNF-α and irritability and between IL-6 and sociability are consistent with previous observations of decreased immune markers with behavioral symptoms in ASD.
“The negative relationships between TNF-α and irritability and between IL-6 and sociability are consistent with previous observations of decreased immune markers with behavioral symptoms in ASD (Heuer et al., 2008).”
From Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder (2016) · cites this paper as Heuer et al., 2008
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References 50 · Cited by 190
- Authors
- Heuer, L., Ashwood, P., Schauer, J., Goines, P., Krakowiak, P., Hertz‐Picciotto, I., Hansen, R., Croen, L. A., Pessah, I. N., & Van de Water, J.
- Affiliations
- University of California, Davis (US)
- Kaiser Permanente (US)
- ORCID
- Venue
- Autism Research
- Publisher
- Wiley
- Published
- 2008-10
- Volume
- 1
- Issue
- 5
- Pages
- 275-283
- ISSN
- 1939-3792 (ISSN-L)
- 1939-3806
- PMC
- PMC2663897
- OpenAlex
- W1988372841
- Cited by
- 190
- References
- 50
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 14 · 2023: 10 · 2022: 12 · 2021: 8 · 2020: 7 · 2019: 9 · 2018: 9 · 2017: 12 · 2016: 14 · 2015: 9 · 2014: 13 · 2013: 15 · 2012: 19
- FWCI
- 5.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Autism Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Environmental Health Sciences (1 P01 ES11269-01, R01ES015359, P01ES011269)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- autism spectrum disorder, immunoglobulin levels, plasma IgG, immunoglobulin A, immunoglobulin E, immune function, developmental delay, aberrant behavior, behavioral symptoms, immune dysfunction
- MeSH terms
- Autistic Disorder, Mental Disorders, Child, Child, Preschool, Female, Humans, Immunoglobulin G, Immunoglobulin M, Male
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