Understanding On Neuroimmunology In Autism Spectrum Disorder
Amaicha Mara Depino, M A Robinson-Agramonte
Published 2015 · Medicine
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Autism spectrum disorders (ASD) are a group of severe pervasive neurodevelopmental disorders (PDD) affecting between 1 and 3 % of pediatric populations. It is characterized by a highly variable impairment in social interaction and verbal and nonverbal communication, as well as by a stereotyped repetitive behavior, learning problems, and aloofness. ASD behavioral symptoms are frequently accompanied by immunological derangements, including cellular immune dysregulation, chronic inflammatory states, and neuroimmune alterations. Currently, the involvement of the immune pathology in autism remains unclear, and we consider that a better understanding would be useful for earlier clinical and therapeutic interventions. The main aim of this chapter is to review the most current aspects regarding the etiology of autism, with particular reference to the contribution of inflammatory events occurring in the periphery and into the brain, and how they can influence the abnormal development of the offspring and modulate the typical behaviors frequently observed in autism.
This paper references
Plasma Cytokine Profiles in Subjects with High-Functioning Autism Spectrum Disorders
K. Suzuki (2011)
The Neurodevelopmental Impact of Prenatal Infections at Different Times of Pregnancy: The Earlier the Worse?
U. Meyer (2007)
T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR
S. Sauer (2008)
Whole blood serotonin in autistic and normal subjects.
G. Anderson (1987)
B Cell Receptor Signaling
黒崎 知博 (2015)
Alterations of the Intestinal Barrier in Patients With Autism Spectrum Disorders and in Their First-degree Relatives
L. de Magistris (2010)
Neurochemical correlates of autistic disorder: a review of the literature.
K. S. Lam (2006)
Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism.
R. Furlano (2001)
Excitatory actions of gaba during development: the nature of the nurture
Y. Ben-Ari (2002)
Macrophage migration inhibitory factor.
J. Baugh (2002)
Effects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flow.
A. Bernardo (2004)
Involvement of dietary bioactive proteins and peptides in autism spectrum disorders.
D. Siniscalco (2013)
Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices
S. Fatemi (2002)
Fyn Promotes Th17 Differentiation by Regulating the Kinetics of RORγt and Foxp3 Expression
A. Ueda (2012)
Gastrointestinal microflora studies in late-onset autism.
S. Finegold (2002)
Low-grade endotoxemia in patients with severe autism
E. Emanuele (2010)
S1P1-mTOR axis directs the reciprocal differentiation of TH1 and regulatory T cells
G. Liu (2010)
The CHARGE Study: An Epidemiologic Investigation of Genetic and Environmental Factors Contributing to Autism
I. Hertz-Picciotto (2006)
Maternal Infection and the Offspring Brain
A. Depino (2006)
Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis
S. Pradhan (1999)
Autism in a child with congenital cytomegalovirus infection
P. I. Markowitz (1983)
Decreased serum levels of transforming growth factor-β1 in patients with autism
K. Okada (2007)
Risperidone-induced weight gain in referred children with autism spectrum disorders is associated with a common polymorphism in the 5-hydroxytryptamine 2C receptor gene.
P. Hoekstra (2010)
Passage of Interleukin-1-Beta Across the Blood-Brain Barrier Is Reduced in Aged Mice: A Possible Mechanism for Diminished Fever in Aging
R. McLay (2000)
Maternal immune activation causes age- and region-specific changes in brain cytokines in offspring throughout development
Paula A. Garay (2013)
GATA-3 Is Involved in the Development of Serotonergic Neurons in the Caudal Raphe Nuclei
J. Hikke van Doorninck (1999)
Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms
P. Ashwood (2006)
Expanding the effector CD4 T-cell repertoire: the Th17 lineage.
L. Harrington (2006)
Possible Association Between Congenital Cytomegalovirus Infection and Autistic Disorder
Y. Yamashita (2003)
Microbiology of regressive autism.
S. Finegold (2012)
Hyperserotonemia and amine metabolites in autistic and retarded children.
H. Hanley (1977)
Spironolactone might be a desirable immunologic and hormonal intervention in autism spectrum disorders.
J. Bradstreet (2007)
A comprehensive functional analysis of PTEN mutations: implications in tumor- and autism-related syndromes.
I. Rodríguez-Escudero (2011)
Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry
I. Sousa (2010)
Th1- and Th2-like cytokines in CD4+ and CD8+ T cells in autism
S. Gupta (1998)
Urinary 5-hydroxyindoleacetic acid and whole blood serotonin and tryptophan in autistic and normal subjects
R. Minderaa (1987)
Gene expression changes in children with autism.
J. Gregg (2008)
Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the determination of platelet serotonin levels
A. Coutinho (2006)
Density and Distribution of Hippocampal Neurotransmitter Receptors in Autism: An Autoradiographic Study
G. Blatt (2001)
Brain meets body: the blood-brain barrier as an endocrine interface.
W. Banks (2012)
Enterocolitis in children with developmental disorders
A. Wakefield (2000)
Impact of innate immunity in a subset of children with autism spectrum disorders: a case control study
H. Jyonouchi (2008)
Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome
P. Ashwood (2011)
HLA-DR4 in families with autism.
L. Lee (2006)
Anti-inflammatory functions of the "apoptotic" caspases.
David Wallach (2010)
Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children.
Helena Parracho (2005)
The immune response in autism: a new frontier for autism research
P. Ashwood (2006)
Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report
T. Buie (2010)
Identifying loci for the overlap between attention-deficit/hyperactivity disorder and autism spectrum disorder using a genome-wide QTL linkage approach.
J. Nijmeijer (2010)
Differential monocyte responses to TLR ligands in children with autism spectrum disorders
A. Enstrom (2010)
Increasing knowledge of PTEN germline mutations: Two additional patients with autism and macrocephaly
G. Herman (2007)
Immune abnormalities in patients with autism
R. P. Warren (1986)
Early Medical History of Children with Autism Spectrum Disorders
Rebecca Niehus (2006)
Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations
M. Butler (2005)
Interleukin-1 beta augments release of norepinephrine, dopamine, and serotonin in the rat anterior hypothalamus
F. Shintani (1993)
Patterns of Complementary and Alternative Medical Therapy Use in Children Diagnosed with Autism Spectrum Disorders
H. Wong (2006)
Studies on 5-hydroxyindole metabolism in autistic and other mentally retarded children.
R. Schain (1961)
Decreased Expression of CD95 (FAS/APO-1) on CD4+ T-lymphocytes from Participants with Autism
H. Engstrom (2003)
Acquired reversible autistic syndrome in acute encephalopathic illness in children.
G. Delong (1981)
Atypical excitation–inhibition balance in autism captured by the gamma response to contextual modulation☆
T. M. Snijders (2013)
Inflammation in pregnancy: its roles in reproductive physiology, obstetrical complications, and fetal injury.
R. Romero (2007)
Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism
F. Torrente (2002)
The interleukin‐23 axis in intestinal inflammation
Philip P. Ahern (2008)
Autism and vitamin D.
J. Cannell (2008)
The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells.
Thomas Hoyler (2012)
Immunological findings in autism.
H. Cohly (2005)
Infections, Toxic Chemicals and Dietary Peptides Binding to Lymphocyte Receptors and Tissue Enzymes are Major Instigators of Autoimmunity in Autism
A. Vojdani (2003)
Hyperserotoninemia and Altered Immunity in Autism
Nancy K Burgess (2006)
Learning modulation by endogenous hippocampal IL‐1: Blockade of endogenous IL‐1 facilitates memory formation
A. Depino (2004)
Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children.
M. Chez (2007)
Pathways underlying the gut-to-brain connection in autism spectrum disorders as future targets for disease management.
C. G. M. de Theije (2011)
The Time of Prenatal Immune Challenge Determines the Specificity of Inflammation-Mediated Brain and Behavioral Pathology
U. Meyer (2006)
Elevated cytokine levels in children with autism spectrum disorder
C. Molloy (2006)
mTOR signaling: At the crossroads of plasticity, memory and disease
C. Hoeffer (2010)
ORIGINAL ARTICLE: The Transcriptome of the Fetal Inflammatory Response Syndrome
Sally A Madsen-Bouterse (2010)
Expression and secretion of antiviral factors by trophoblast cells following stimulation by the TLR-3 agonist, Poly(I : C).
V. Abrahams (2006)
The Interleukin‐23 / Interleukin‐17 axis in intestinal inflammation
K. Maloy (2008)
Treatment of Late Onset Autism as a Consequence of Probable Autommune Processes Related to Chronic Bacterial Infection
E. B. Matarazzo (2002)
Interleukin-1 stimulates the release of dopamine and dihydroxyphenylacetic acid from the hypothalamus in vivo.
P. S. MohanKumar (1991)
T-cell subsets (Th1 versus Th2).
S. Romagnani (2000)
Intestinal Lymphocyte Populations in Children with Regressive Autism: Evidence for Extensive Mucosal Immunopathology
P. Ashwood (2004)
Gastrointestinal Conditions in Children With Autism Spectrum Disorder: Developing a Research Agenda
D. Coury (2012)
The potential importance of steroids in the treatment of autistic spectrum disorders and other disorders involving mercury toxicity.
M. Geier (2005)
Epidemiology of autistic disorder and other pervasive developmental disorders.
E. Fombonne (2005)
Effects of tryptophan depletion in drug-free adults with autistic disorder.
C. McDougle (1996)
Peripheral and central inflammation in autism spectrum disorders
A. Depino (2013)
Neuroinflammation: A Common Pathway in CNS Diseases as Mediated at the Blood-Brain Barrier
M. Erickson (2012)
Abnormal intestinal permeability in children with autism
P. D’Eufemia (1996)
Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children
D. Chugani (1999)
Macrophage Migration Inhibitory Factor and Autism Spectrum Disorders
E. Grigorenko (2008)
Moderators, mediators, and other predictors of risperidone response in children with autistic disorder and irritability.
L. E. Arnold (2010)
Effects of interleukin-1β and mild stress on alterations of norepinephrine, dopamine and serotonin neurotransmission: a regional microdialysis study
Z. Merali (1997)
Intravenous Immune Globulin Therapy for Neurologic Diseases
M. Dalakas (1997)
DR-positive T cells in autism: association with decreased plasma levels of the complement C4B protein.
R. P. Warren (1995)
Complementary Alternative Medicine for Children with Autism: A Physician Survey
Allison Golnik (2009)
State of the art; microbiology in health and disease. Intestinal bacterial flora in autism.
S. Finegold (2011)
Short-Term Benefit From Oral Vancomycin Treatment of Regressive-Onset Autism
R. Sandler (2000)
Decreased cellular IL-23 but not IL-17 production in children with autism spectrum disorders
C. Onore (2009)
Early and adult hippocampal TGF-β1 overexpression have opposite effects on behavior
A. Depino (2011)
Neuronal nicotinic acetylcholine receptor subunits in autism: an immunohistochemical investigation in the thalamus
M. A. Ray (2005)
The Expression of Caspases is Enhanced in Peripheral Blood Mononuclear Cells of Autism Spectrum Disorder Patients
D. Siniscalco (2012)
Th17: the third member of the effector T cell trilogy.
E. Bettelli (2007)
Brief report: Onset at age 14 of a typical autistic syndrome. A case report of a girl with herpes simplex encephalitis
C. Gillberg (1986)
Generation of Th17 from human naive CD4+ T cells preferentially occurs from FOXP3+ Tregs upon costimulation via CD28 or CD5.
M. Ayyoub (2012)
Cytokines and CNS Development
B. Deverman (2009)
Neuroglial activation and neuroinflammation in the brain of patients with autism
D. L. Vargas (2005)
Caspase‐1 inflammasomes in infection and inflammation
M. Lamkanfi (2007)
Elevated levels of measles antibodies in children with autism.
V. Singh (2003)
Glial cell influence on the human blood‐brain barrier
A. Prat (2001)
Autism: neuropathology, alterations of the GABAergic system, and animal models.
C. Schmitz (2005)
Plasma increase of interleukin-12 and interferon-gamma. Pathological significance in autism
V. Singh (1996)
Is there more to gaba than synaptic inhibition?
D. F. Owens (2002)
The association and linkage of the HLA-A2 class I allele with autism.
A. Torres (2006)
The Neurobiology of Autism
C. Pardo (2007)
Immunity, neuroglia and neuroinflammation in autism
C. Pardo (2005)
Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: Relevance to autism spectrum disorder
D. MacFabe (2011)
The neurobiology of infantile autism.
A. L. Ciaranello (1995)
The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells.
J. Mjösberg (2012)
Reduced Incidence of Prevotella and Other Fermenters in Intestinal Microflora of Autistic Children
Dae-Wook Kang (2013)
Autistic Subjects with Comorbid Epilepsy: A Possible Association with Viral Infections
Y. Barak (1999)
Cytokine-induced sickness behaviour: mechanisms and implications
J. Konsman (2002)
Increased frequency of the extended or ancestral haplotype B44-SC30-DR4 in autism.
W. W. Daniels (1995)
Tumor necrosis factor alpha, interleukin 1 and related cytokines in brain development: normal and pathological.
J. Merrill (1992)
A case study of the cognitive and behavioral deficits of temporal lobe damage in herpes simplex encephalitis
Margaret K. Greer (1989)
Autism in children with congenital rubella
S. Chess (1971)
Serotonin and amino acid content in platelets of autistic children
L. Rolf (1993)
Pervasive developmental disorders in preschool children.
S. Chakrabarti (2001)
Dysregulated Innate Immune Responses in Young Children with Autism Spectrum Disorders: Their Relationship to Gastrointestinal Symptoms and Dietary Intervention
H. Jyonouchi (2005)
Maternal Infection Requiring Hospitalization During Pregnancy and Autism Spectrum Disorders
H. Atladóttir (2010)
Involvement of the PRKCB1 gene in autistic disorder: significant genetic association and reduced neocortical gene expression
C. Lintas (2009)
Pyrosequencing study of fecal microflora of autistic and control children.
S. Finegold (2010)
mTOR at the crossroads of T cell proliferation and tolerance.
A. Mondino (2007)
Th1/Th2 cells, their associated molecules and role in pathophysiology.
P. Romagnani (2000)
Use of Complementary and Alternative Medicine Among Children Recently Diagnosed with Autistic Spectrum Disorder
S. Levy (2003)
Decreased transforming growth factor beta1 in autism: A potential link between immune dysregulation and impairment in clinical behavioral outcomes
P. Ashwood (2008)
Seasonal Variation in Neuroendocrine and Mood Responses to IV L-Tryptophan in Depressed Patients and Healthy Subjects
A. Cappiello (1996)
Expression of inflammatory cytokines, Bcl2 and cathepsin D are altered in lymphoblasts of autistic subjects.
M. Malik (2011)
Familial Clustering of Autoimmune Disorders and Evaluation of Medical Risk Factors in Autism
A. Comi (1999)
REGULATION OF IMMUNE RESPONSES BY TGF-β*
J. Letterio (1998)
Inflammation-Driven Reprogramming of CD4+Foxp3+ Regulatory T Cells into Pathogenic Th1/Th17 T Effectors Is Abrogated by mTOR Inhibition in vivo
E. Yurchenko (2012)
Immune transcriptome alterations in the temporal cortex of subjects with autism
K. Garbett (2008)
Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene–environment interactions
M. D’Amelio (2005)
Behavioral effects of Org 2766, a synthetic analog of the adrenocorticotrophic hormone (4–9), in 14 outpatient autistic children
J. Buitelaar (1990)
Prenatal origins of individual variation in behavior and immunity
C. Coe (2005)
GABAA Receptor Downregulation in Brains of Subjects with Autism
S. Fatemi (2009)
Dysregulation of Reelin and Bcl-2 Proteins in Autistic Cerebellum
S. Fatemi (2001)
Early-Life Programming of Later-Life Brain and Behavior: A Critical Role for the Immune System
S. Bilbo (2009)
Gastrointestinal flora and gastrointestinal status in children with autism -- comparisons to typical children and correlation with autism severity
J. Adams (2011)
Coordination of tolerogenic immune responses by the commensal microbiota.
J. Round (2010)
Amniotic fluid chemokines and autism spectrum disorders: An exploratory study utilizing a Danish Historic Birth Cohort
M. Abdallah (2012)
Pervasive developmental disorders in preschool children: confirmation of high prevalence.
S. Chakrabarti (2005)
Autism and gastrointestinal symptoms
K. Horváth (2002)
Response to steroid therapy in autism secondary to autoimmune lymphoproliferative syndrome.
S. Shenoy (2000)
Autistic traits in simplex and multiplex autism families: Focus on unaffected relatives
R. Hoekstra (2010)
Evidence for an infectious etiology in autism
A. Ring (1997)
Frequency of CD4+CD25high Regulatory T Cells in the Peripheral Blood of Egyptian Children With Autism
G. Mostafa (2010)
Elevated immune response in the brain of autistic patients
X. Li (2009)
Linkage and candidate gene studies of autism spectrum disorders in European populations
R. Holt (2010)
Infection in the First 2 Years of Life and Autism Spectrum Disorders
N. Rosen (2007)
Common increase of GATA-3 level in PC-12 cells by three teratogens causing autism spectrum disorders
U. Rout (2009)
Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid
Cheng-ming Sun (2007)
Autism as one of several disabilities in two children with congenital cytomegalovirus infection.
S. Ivarsson (1990)
Autism and congenital cytomegalovirus
E. Stubbs (1984)
Autistic symptoms in a child with congenital cytomegaloviras infection
E. Stubbs (1978)
Brief report: Autism and herpes simplex encephalitis
M. Ghaziuddin (1992)
A phylogenetic and functional overview of inflammatory caspases and caspase-1-related CARD-only proteins.
K. Kersse (2007)
A review of the fetal brain cytokine imbalance hypothesis of schizophrenia.
U. Meyer (2009)
TH17 cells in development: an updated view of their molecular identity and genetic programming
C. Dong (2008)
Treatment of children with autism with intravenous immunoglobulin.
S. Gupta (1999)
Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism
Luciana Lucchina (2014)
Autism and the immune system.
T. van Gent (1997)
Intravenous Immunoglobulin Treatment of Children With Autism
A. Plioplys (1998)
Receptor tyrosine kinases and the regulation of macrophage activation
P. Correll (2004)
Constipation with acquired megarectum in children with autism.
N. Afzal (2003)
Nicotinic receptor abnormalities in the cerebellar cortex in autism.
M. Lee (2002)
Molecular analysis of nicotinic receptor expression in autism.
C. Martín-Ruiz (2004)
Expression of GABAB Receptors Is Altered in Brains of Subjects with Autism
S. Fatemi (2008)
Microbial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function
Torsten Olszak (2012)
This paper is referenced by
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