Abstract
Innate/adaptive immune responses and transcript profiles of peripheral blood monocytes
were studied in ASD children who exhibit fluctuating behavioral symptoms following
infection and other immune insults (ASD/Inf, N=30). The ASD/Inf children with persistent gastrointestinal symptoms (ASD/Inf+GI, N=19), revealed less production of proinflammatory and counter-regulatory cytokines
with stimuli of innate immunity and marked changes in transcript profiles of monocytes
as compared to ASD/no-Inf (N=28) and normal (N=26) controls. This included a 4–5 fold up-regulation of chemokines (CCL2 and CCL7),
consistent with the production of more CCL2 by ASD/Inf+GI cells. These results indicate dysregulated innate immune defense in the ASD/Inf+GI children, rendering them more vulnerable to common microbial infection/dysbiosis
and possibly subsequent behavioral changes.
Abbreviations:
α-LA (α-lactoalbumin), β-LG (β-lactoglobulin), AC (allergic conjunctivitis), AR (allergic rhinitis), ASD (autism spectrum disorder), ASD-IS (ASD-immune subtype), BMDM cells (bone marrow derived microglial cells), CNS (central nervous system), CNV (copy number variation), CRS (chronic rhinosinusitis), CVID (common variable immunodeficiency), FA (food allergy), FP (food protein), FPIES (food protein induced enterocolitis syndrome), GI (gastrointestinal), GWAS (genome wide association studies), IBD (inflammatory bowel disease), IL (interleukin), IVIG (intravenous immunoglobulin), MS (multiple sclerosis), NJMS (New Jersey Medical School), PB (peripheral blood), PBMCs (peripheral blood mononuclear cells), ROM (recurrent otitis media), SD (standard deviation), SNP (single nucleotide polymorphism), SPAD (specific polysaccharide antibody deficiency), TLR (toll-like receptor), TNF (tumor necrosis factor), sTNFRII (soluble TNF-receptor II), TGF-β (transforming growth factor-β), UMDNJ (University of Medicine and Dentistry of New Jersey)Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of NeuroimmunologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Genetic association study of KREMEN1 and DKK1 and schizophrenia in a Japanese population.Schizophr. Res. 2010; 118: 113-117
- Altered T cell responses in children with autism.Brain Behav. Immun. 2011; 5: 840-849
- Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders.J. Neuroimmunol. 2011; 232: 196-199
- Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms.J. Neuroimmunol. 2006; 173: 126-134
- Neonatal behavioral changes in rats with gestational exposure to lipopolysaccharide: a prenatal infection model for developmental neuropsychiatric disorders.Schizophr. Bull. 2010; ([Epub ahead of print])
- Early life programming and neurodevelopmental disorders.Biol. Psychiatry. 2010; 68: 314-319
- The functional significance of the TGM2 gene in schizophrenia: a correlation of SNPs and circulating IL-2 levels.J. Neuroimmunol. 2011; 232: 5-7
- Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes.PLoS Genet. 2009; 5: e1000536
- Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report.Pediatrics. 2010; 125: S1-S18
- Ocular allergy: diagnosis and treatment.Ophthalmol. Clin. N. Am. 2005; 18 (v.): 485-492
- Multiplex ligation-dependent probe amplification for genetic screening in autism spectrum disorders: efficient identification of known microduplications and identification of a novel microduplication in ASMT.BMC Med. Genomics. 2008; 1: 50
- Copy-number variations associated with neuropsychiatric conditions.Nature. 2008; 455: 919-923
- Toll-like receptors in the brain and their potential roles in neuropathology.Immunol. Cell Biol. 2007; 85: 476-480
- Autism spectrum disorders in tuberous sclerosis: pathogenetic pathways and implications for treatment.J. Child Neurol. 2010; 25: 873-880
- From bone marrow to microglia: barriers and avenues.Trends Immunol. 2008; 29: 227-234
- Induction of toll-like receptor 3-mediated immunity during gestation inhibits cortical neurogenesis and causes behavioral disturbances.MBio. 2010; 1
- Circulating monocytes engraft in the brain, differentiate into microglia and contribute to the pathology following meningitis in mice.Brain. 2006; 129: 2394-2403
- The genetics of autism: key issues, recent findings, and clinical implications.Psychiatr. Clin. N. Am. 2010; 33: 83-105
- Differential monocyte responses to TLR ligands in children with autism spectrum disorders.Brain Behav. Immun. 2010; 24: 64-71
- The role of MeCP2 in brain development and neurodevelopmental disorders.Curr. Psychiatry Rep. 2010; 12: 127-134
- Gene expression changes in children with autism.Genomics. 2008; 91: 22-29
- Activation of the maternal immune system induces endocrine changes in the placenta via IL-6.Brain Behav. Immun. 2011; 4: 604-615
- A study of circulating gliadin antibodies in schizophrenia among a Chinese population.Schizophr. Bull. 2010; ([Epub ahead of print])
- Mutation screening of melatonin-related genes in patients with autism spectrum disorders.BMC Med. Genomics. 2010; 3: 10
- Food allergy and autism spectrum disorders: is there a link?.Curr. Allergy Asthma Rep. 2009; 9: 194-201
- Autism spectrum disorders and allergy: observation from a pediatric allergy/immunology clinic.Expert. Rev. Clin. Immunol. 2010; 6: 397-411
- Aberrant responses to TLR agonists in pediatric IBD patients; the possible association with increased production of Th1/Th17 cytokines in response to candida, a luminal antigen.Pediatr. Allergy Immunol. 2010; 21: e747-e755
- Impact of innate immunity in a subset of children with autism spectrum disorders: a case control study.J. Neuroinflammation. 2008; 5: 52
- Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders.J. Pediatr. 2005; 146: 605-610
- Dysregulated innate immune responses in young children with autism spectrum disorders: their relationship to gastrointestinal symptoms and dietary intervention.Neuropsychobiology. 2005; 51: 77-85
- Suboptimal responses to dietary intervention in children with autism spectrum disorders and Non-IgE mediated food allergy.in: Zhao L.B. Autism Research Advances. Nova Science Publishers, Inc, 2007: 169-184
- EGR3 as a potential susceptibility gene for schizophrenia in Korea.Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010; 153B: 1355-1360
- Th17 cells in inflammation.Int. Immunopharmacol. 2011; 11: 319-322
- Association of calcineurin A gamma subunit (PPP3CC) and early growth response 3 (EGR3) gene polymorphisms with susceptibility to schizophrenia in a Japanese population.Psychiatry Res. 2011; 185: 16-19
- A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells.Cell. 2010; 143: 527-539
- Identifying and managing rhinitis and its subtypes: allergic and nonallergic components—a consensus report and materials from the Respiratory and Allergic Disease Foundation.Curr. Med. Res. Opin. 2006; 22: 2541-2548
- Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs.J. Immunol. 2004; 173: 3916-3924
- Monocytes and macrophages regulate immunity through dynamic networks of survival and cell death.J. Innate Immun. 2010; 2: 204-215
- The myeloid cells of the central nervous system parenchyma.Nature. 2010; 468: 253-262
- Bone-marrow-derived cell differentiation into microglia: a study in a progressive mouse model of Parkinson's disease.Neurobiol. Dis. 2007; 28: 316-325
- New technologies provide insights into genetic basis of psychiatric disorders and explain their co-morbidity.Psychiatr. Danub. 2010; 22: 190-192
- The contribution of rare diseases to understanding the epidemiology of neurodevelopmental disabilities.Adv. Exp. Med. Biol. 2010; 686: 433-453
- Monocyte-mediated defense against microbial pathogens.Annu. Rev. Immunol. 2008; 26: 421-452
- Phenotypic expression of autoimmune autistic disorder (AAD): a major subset of autism.Ann. Clin. Psychiatry. 2009; 21: 148-161
- Key role for gene dosage and synaptic homeostasis in autism spectrum disorders.Trends Genet. 2010; 26: 363-372
- Monocyte subtypes predict clinical course and prognosis in human stroke.J. Cereb. Blood Flow Metab. 2009; 29: 994-1002
- Neuroglial activation and neuroinflammation in the brain of patients with autism.Ann. Neurol. 2005; 57: 67-81
- Fragile X: leading the way for targeted treatments in autism.Neurotherapeutics. 2010; 7: 264-274
- Innate immunity in inflammatory bowel disease.World J. Gastroenterol. 2007; 13: 5577-5580
- Intrauterine infection/inflammation and perinatal brain damage: role of glial cells and Toll-like receptor signaling.J. Neuroimmunol. 2010; 229: 16-25
Article info
Publication history
Published online: August 02, 2011
Accepted:
July 6,
2011
Received in revised form:
June 26,
2011
Received:
February 16,
2011
Identification
Copyright
© 2011 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
