The Immune System, Cytokines, And Biomarkers In Autism Spectrum Disorder
Anne Masi, Nicholas Glozier, Russell C Dale, Adam J Guastella
Published 2017 · Medicine, Psychology
Download PDFAnalyze on Scholarcy
Abstract Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors. Heterogeneity of presentation is a hallmark. Investigations of immune system problems in ASD, including aberrations in cytokine profiles and signaling, have been increasing in recent times and are the subject of ongoing interest. With the aim of establishing whether cytokines have utility as potential biomarkers that may define a subgroup of ASD, or function as an objective measure of response to treatment, this review summarizes the role of the immune system, discusses the relationship between the immune system, the brain, and behavior, and presents previously-identified immune system abnormalities in ASD, specifically addressing the role of cytokines in these aberrations. The roles and identification of biomarkers are also addressed, particularly with respect to cytokine profiles in ASD.
This paper references
Meta-Analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects
Brian J. Miller (2011)
Comorbidity in autism spectrum disorder: A literature review
Arlene Mannion (2013)
The Role of the Immune System in Autism Spectrum Disorder
Amory Meltzer (2017)
Model of autism: increased ratio of excitation/inhibition in key neural systems.
John L Rubenstein (2003)
Evidence supporting an altered immune response in ASD.
Jennifer Mead (2015)
Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome
Paul Ashwood (2011)
Neuroglial activation and neuroinflammation in the brain of patients with autism.
Diana L. Torres Vargas (2005)
Rett syndrome and other autism spectrum disorders—brain diseases of immune malfunction?
Noel C. Derecki (2010)
The NIMH Research Domain Criteria (RDoC) Project: precision medicine for psychiatry.
Thomas R. Insel (2014)
Cytokine, sickness behavior, and depression. Immunol
R Dantzer (2009)
Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders
Paul Ashwood (2011)
Pro- versus anti-inflammatory cytokines: myth or reality.
J. M. Cavaillon (2001)
[Affective disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association -- diagnostic and statistical manual of mental disorders].
Jolanta Rabe-Jabłońska (1993)
Differentiation of effector CD4 T cell populations (*).
Jinfang Zhu (2010)
Sleep disorders and autism spectrum disorder Psychiatric symptoms and comorbidities in autism spectrum disorder
S Miano (2016)
Immune System, Cytokines, and Biomarkers in ASD
T-cell subsets (Th1 versus Th2).
Sergio Romagnani (2000)
Nat Rev Genet
H Kitano (2004)
Role of interleukin-6 in stress, sleep, and fatigue.
Nicolas Rohleder (2012)
In Search of Cellular Immunophenotypes in the Blood of Children with Autism
Paul Ashwood (2011)
IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation
Hongen Wei (2011)
Chemokines, a family of chemotactic cytokines.
Dana T Graves (1995)
Cytokine, sickness behavior, and depression.
Robert Dantzer (2006)
Hiroaki Kitano (2004)
Maternal infection during pregnancy and risk of autism spectrum disorders: A systematic review and meta-analysis
Hai-yin Jiang (2016)
Cytokine-Induced Sickness Behavior: Where Do We Stand?
Robert Dantzer (2001)
Biomarkers and surrogate endpoints: preferred definitions and conceptual framework.
Arthur J. Jr. Atkinson (2001)
Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, reduces the progression of experimental osteoarthritis in guinea pigs.
Tetsuya Kobayashi (2005)
National Academy of Sciences. The national academies collection: reports funded by national institutes of health
Mechanisms Underlying the Rapid Peroxisome Proliferator-Activated Receptor-γ-Mediated Amyloid Clearance and Reversal of Cognitive Deficits in a Murine Model of Alzheimer's Disease
Shweta Mandrekar-Colucci (2012)
Double-blind placebo-controlled trial of pentoxifylline added to risperidone: Effects on aberrant behavior in children with autism
Shahin Akhondzadeh (2010)
The pro- and anti-inflammatory properties of the cytokine interleukin-6.
Jürgen Scheller (2011)
Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don't know
Yufang Shi (2006)
Interferon-gamma: an overview of signals, mechanisms and functions.
Kate Schroder (2004)
Medical comorbidities in autism: Challenges to diagnosis and treatment
Margaret L. Bauman (2011)
Cytokine dysregulation in autism spectrum disorders (ASD): possible role of the environment.
Paula E. Goines (2013)
The neuropsychiatric effects of treatment with interleukin-2 and lymphokine-activated killer cells.
Kirk D. Denicoff (1987)
From inflammation to sickness and depression: when the immune system subjugates the brain
Rd Dantzer (2008)
Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease.
Mark D Turner (2014)
Biomarkers Definitions Working Group Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework
Elevated cytokine levels in children with autism spectrum disorder
Cynthia A. Molloy (2006)
Peripheral Biomarkers Revisited: Integrative Profiling of Peripheral Samples for Psychiatric Research
Akiko Hayashi-Takagi (2014)
Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors.
Hongen Wei (2012)
Celecoxib as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial
Mahtab Asadabadi (2012)
IL-1β–Mediated Signals Preferentially Drive Conversion of Regulatory T Cells but Not Conventional T Cells into IL-17–Producing Cells
Lequn Li (2010)
Th1- and Th2-like cytokines in CD4+ and CD8+ T cells in autism
Sudhir Gupta (1998)
Molecular Biology of the Cell 4th edition
Martin Raff (2002)
Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders
Hjördís Ósk Atladóttir (2009)
Inflammatory Cytokines: Potential Biomarkers of Immunologic Dysfunction in Autism Spectrum Disorders
Ningan Xu (2015)
Interleukin-12 (IL-12p70) Promotes Induction of Highly Potent Th1-Like CD4+CD25+ T Regulatory Cells That Inhibit Allograft Rejection in Unmodified Recipients
Nirupama D. Verma (2014)
A Meta-Analysis of Cytokines in Major Depression
Yekta Dowlati (2010)
Plasma level of transforming growth factor β 1 in children with autism spectrum disorder
Tarek Mohamed El Gohary (2015)
The immune system's role in the biology of autism
Paula E. Goines (2010)
Altered Cytokine and BDNF Levels in Autism Spectrum Disorder
Stefano Ricci (2013)
Maternal immune activation: Implications for neuropsychiatric disorders
Myka Estes (2016)
Depressed lymphocyte responsiveness in autistic children
E. Gene Stubbs (1977)
Toward an immune-mediated subtype of autism spectrum disorder
Christopher J McDougle (2015)
Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis
Alfonse T. Masi (2014)
An investigation of comorbid psychological disorders, sleep problems, gastrointestinal symptoms and epilepsy in children and adolescents with autism spectrum disorder: A two year follow-up
Arlene Mannion (2016)
Change in plasma cytokine levels during risperidone treatment in children with autism.
Jae Eun Choi (2014)
Neonatal Cytokine Profiles Associated With Autism Spectrum Disorder
Paula Krakowiak (2017)
Sleep Disorders and Autism Spectrum Disorder
Silvia Miano (2016)
Immune system to brain signaling: neuropsychopharmacological implications.
Lucile Capuron (2011)
Inflammation in children and adolescents with neuropsychiatric disorders: a systematic review.
Rachel H.B. Mitchell (2014)
Elevated immune response in the brain of autistic patients
Xiaohong Li (2009)
Increased IgG4 levels in children with autism disorder
Amanda M. Enstrom (2009)
Immune mediated conditions in autism spectrum disorders
Ousseny Zerbo (2015)
The role of interleukin-8 in inflammation and mechanisms of regulation.
Michael Bickel (1993)
Interferon-γ: an overview of signals, mechanisms and functions
Kate Schroder (2004)
IL-1β Processing in Host Defense: Beyond the Inflammasomes
Mihai G. Netea (2010)
The national academies collection: reports funded by national institutes of health
Altered T cell responses in children with autism
Paul Ashwood (2011)
Neuroinflammation and regulation of glial glutamate uptake in neurological disorders.
Sébastien Tilleux (2007)
Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children.
Michael G. Chez (2007)
Commentary: Structural and functional features of central nervous system lymphatic vessels
James Jeffrey Bradstreet (2015)
The role of the human prefrontal cortex in social cognition and moral judgment.
Chad E. Forbes (2010)
Plasma Cytokine Profiles in Subjects with High-Functioning Autism Spectrum Disorders
Katsuaki Suzuki (2011)
Role of Inflammation in the Development of Neuropsychiatric Symptom Domains: Evidence and Mechanisms.
Lucile Capuron (2017)
Unexpected role of interferon-γ in regulating neuronal connectivity and social behavior
Anthony J. Filiano (2016)
DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDERS, FIFTH EDITION
Attari Abbas (2013)
Therapeutic signposts: using biomarkers to guide better treatment of schizophrenia and other psychotic disorders.
Richard B Banati (2009)
Decreased transforming growth factor beta1 in autism: A potential link between immune dysregulation and impairment in clinical behavioral outcomes
Paul Ashwood (2008)
Innate or Adaptive Immunity? The Example of Natural Killer Cells
Eric Vivier (2011)
Recent Advances in Underlying Pathologies Provide Insight into Interleukin-8 Expression-Mediated Inflammation and Angiogenesis
Basit Saleem Qazi (2011)
Cytokine Alterations in Bipolar Disorder: A Meta-Analysis of 30 Studies
Amirhossein Modabbernia (2013)
A pilot double-blind placebo-controlled trial of pioglitazone as adjunctive treatment to risperidone: Effects on aberrant behavior in children with autism
Ali Ghaleiha (2015)
Activation of the Inflammatory Response System in Autism
Jan Croonenberghs (2002)
Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample.
Emily Simonoff (2008)
Reduced levels of immunoglobulin in children with autism correlates with behavioral symptoms.
Luke S. Heuer (2008)
Altered gene expression and function of peripheral blood natural killer cells in children with autism
Amanda M. Enstrom (2009)
Understanding on Neuroimmunology in Autism Spectrum Disorder
Amaicha Mara Depino (2015)
Biomarkers in autism spectrum disorder: the old and the new
Barbara Ruggeri (2013)
Neuron-microglia signaling: Chemokines as versatile messengers
Knut Biber (2008)
Interactions of innate and adaptive immunity in brain development and function
Anthony J. Filiano (2015)
Brain development in autism: early overgrowth followed by premature arrest of growth.
Eric Courchesne (2004)
Molecular Biology of the Cell
John Dudley Davies (1983)
Psychiatric symptoms and comorbidities in autism spectrum disorder
Luigi Mazzone (2016)
Biological basis of the behavior of sick animals
Benjamin L Hart (1988)
Targeting the “Cytokine Storm” for Therapeutic Benefit
Riccardo V. D’Elia (2013)
Maternal Infection Requiring Hospitalization During Pregnancy and Autism Spectrum Disorders
Hjördís Ósk Atladóttir (2010)
This paper is referenced by
Immune System Benefits
Sarvodaya Tripathy (2019)
Endogenous Retroviruses Activity as a Molecular Signature of Neurodevelopmental Disorders
Emanuela Balestrieri (2019)
From neurology to oncology: what have in common autism and cancer? the role of oncogenes, immune system and microbiota
Marco Ruggiero (2018)
Inhibition of tyrosine kinase signaling by tyrphostin AG126 downregulates the IL-21/IL-21R and JAK/STAT pathway in the BTBR mouse model of autism.
Sheikh Fahad Ahmad (2019)
Enhancement of T Follicular Helper Cell-Mediated Humoral Immunity Reponses During Development of Experimental Autoimmune Myasthenia Gravis
Ying-zhe Cui (2019)
Immune imbalance of global gene expression, and cytokine, chemokine and selectin levels in the brains of offspring with social deficits via maternal immune activation
P-T Hsueh (2018)
Transcriptome signatures from discordant sibling pairs reveal changes in peripheral blood immune cell composition in Autism Spectrum Disorder
Michele Filosi (2020)
Data-Driven Diagnostics and the Potential of Mobile Artificial Intelligence for Digital Therapeutic Phenotyping in Computational Psychiatry.
Peter Washington (2019)
Neuroimmune and Inflammatory Signals in Complex Disorders of the Central Nervous System
Ana Clara Liberman (2018)
Immunity and autoantibodies of a mouse strain with autistic-like behavior
Mohammad Nizam Uddin (2020)
Sulforaphane as an adjunctive treatment for irritability in Autism Spectrum Disorder: a randomized, double-blind, placebo-controlled clinical trial.
Sara Momtazmanesh (2020)
Autism and KIR genes of the human genome: A brief meta-analysis
Najmeh Pirzadroozbahani (2018)
Lipopolysaccharide-induced inflammation leads to acute elevations in pro-inflammatory cytokine expression in a mouse model of Fragile X syndrome
Samantha L. Hodges (2020)
Hesperetin and it nanocrystals ameliorate social behavior deficits and oxido-inflammatory stress in rat model of autism
Rashin Khalaj (2018)
Modulation of Immunological Pathways in Autistic and Neurotypical Lymphoblastoid Cell Lines by the Enteric Microbiome Metabolite Propionic Acid
Richard Eugene Frye (2017)
ارزیابی ایمنی خاطره و اندازه گیری سطح سرمی آنتیبادی علیه آنتیژن سطحی ویروس هپاتیت B در کودکان مبتلا به اوتیسم در مقایسه با گروه کنترل
شهرام برفی (2019)
Social impairments in autism spectrum disorder are related to maternal immune history profile
Sushil Patel (2017)
Alterations in plasma cytokine levels in chinese children with autism spectrum disorder.
Chun-chun Hu (2018)
Tics and Tourette: a clinical, pathophysiological and etiological review
Russell C Dale (2017)
Fetal and Infancy Growth Pattern, Cord and Early Childhood Plasma Leptin, and Development of Autism Spectrum Disorder in the Boston Birth Cohort.
Ramkripa Raghavan (2018)
Co-occurring medical conditions among individuals with ASD-associated disruptive mutations
Evangeline C. Kurtz-Nelson (2020)
5-aminoisoquinolinone attenuates social behavior deficits and immune abnormalities in the BTBR T+ Itpr3tf/J mouse model for autism
Sheikh F Ahmad (2020)
Expression Analysis of Protein Inhibitor of Activated STAT ( PIAS) Genes in Autistic Patients
Mohammad Mahdi Eftekharian (2018)
Dioxins as potential risk factors for autism spectrum disorder.
Zhiling Guo (2018)
Immunological Dysfunction in Autism Spectrum Disorder: A Potential Target for Therapy
Josemar Marchezan (2018)
The influence of neuroinflammation in Autism Spectrum Disorder
Samantha M. Matta (2019)
Maternal exposure to low dose BDE209 and Pb mixture induced neurobehavioral anomalies in C57BL/6 male offspring.
Yuanhong Chen (2019)
Early Disruption of the Microbiome Leading to Decreased Antioxidant Capacity and Epigenetic Changes: Implications for the Rise in Autism
Rebecca S. Eshraghi (2018)
From bedside to bench and back: Translating ASD models.
Hayley P Drozd (2018)
Altered Microbiota-GALT Communication in IBD and ASD: Changes in IELs and AhR/ARNT Gene Polymorphism
Elizabeth M. Sajdel-Sulkowska (2019)
Le dépistage précoce du trouble du spectre de l’autisme chez les jeunes enfants
Lonnie Zwaigenbaum (2019)
Bridging the Gap Between Physical Health and Autism Spectrum Disorder
Regina Sala (2020)See more