Council for Nutritional and Environmental Medicine, Mo i Rana, Norway, 2 Department of Pediatrics, Faculty of Medicine,
Assiut University, Assiut, Egypt, 3 Department of Neurological and Movement Science, University of Verona, Verona, Italy,
4
Institute of Chronic Illnesses, Inc., Silver Spring, MD, USA, 5 Departamento de Zoologa, Facultad de Ciencias
Naturales y Oceanogrficas, Universidad de Concepcin, Concepcin, Chile,
* Email: bjorklund@conem.org
Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder with a complex pathogenesis. Many
studies over the last four decades have recognized altered immune responses among individuals diagnosed with ASD. The purpose
of this critical and comprehensive review is to examine the hypothesis that immune dysfunction is frequently present in those with
ASD. It was found that often individuals diagnosed with ASD have alterations in immune cells such as T cells, B cells, monocytes,
natural killer cells, and dendritic cells. Also, many individuals diagnosed with ASD have alterations in immunoglobulins and increased
autoantibodies. Finally, a significant portion of individuals diagnosed with ASD have elevated peripheral cytokines and chemokines
and associated neuroinflammation. In conclusion, immune dysregulation and inflammation are important components in the
diagnosis and treatment of ASD.
INTRODUCTION
Autism spectrum disorder (ASD) is considered
a complex and heterogeneous neurologic disorder,
showing features of core abnormalities in social
relationship and communication, repetitive behavior
and deficits in verbal and nonverbal interaction, with
stereotyped behaviors and interests and even visual
dysfunction (APA 2013, Wu et al. 2015, Bakroon and
Lakshminarayanan 2016). The pathogenesis of ASD is
complex and controversial, and both nutritional and
immune causes have been recently associated with this
complex pathology (Hsiao 2013, Endreffy et al. 2016,
Fujiwara et al. 2016, Zerbo et al. 2016). Controversial
issues arose from attempting to distinguishing between
childrens and adults ASD, and particularly Asperger
syndrome with high functioning autism in adults, where
language delays may be used to distinguish the two
pathologies, as the poor performance on language tests
also challenges the assumption that early language
development in Asperger syndrome is essentially normal
(Howlin 2003, BaronCohem and Wheelwright 2004).
Immune system and neuroinflammation appear to play
Received 31 December 2015, accepted 6 September 2016
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Table I. Overview of the studies to date detailing a relationship between ASD and immune function
IMMUNE CELLS
TYPE/SUBTYPE
EXPERIMENTAL
SETTING
EVIDENCE
REFERENCES
Mouse model
CD4+
Blood-ASD
CD8+
Blood-ASD
Colonic C8 cells
and gut T-cells
Gut specimen
CD4+CD25high
regulatory T cells
B-cell
Response to
estrogens and
DHT
ASD subjects
Granulocytes
Neutrophils
Newborns
CD57+CD3-
Th17
T-cell
Natural killer
cells (NK)
Monocytes
Innate cells
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NK, NKT
59 adult patients
with ASD
CD25 expression
Monocytes,
neopterin
31 ASD children
Innate immunity
ASD children
ASD subjects
Dysregulated cytokines
(TNF-, IL-8, IL-9, IL-13, IL-15)
Cytokine levels
Chemokine MCP-1
Chemokines RANTES, MIP-1
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CONCLUSIONS
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