Background: The evidence based supports that multifactorial and complex immune interactions
play a role in autism spectrum disorders (ASD), but contradictory findings are also reported.
Objective: The aim of this selective review was to identify trends in the research literature on this
topic, focusing on immunology and other aberrations with respect to the different ASD subtypes.
Methods: This selective review is based on original and review articles written in English and identified
in literature searches of PubMed.
Results: Several studies have found that the risk of ASD is greater among children whose mothers suffered
from autoimmune diseases while pregnant. Moreover, individuals with ASD show increased levels
of antibodies that are specific for several specific proteins. Studies also show that mothers of children
with ASD have antibodies against fetal brain proteins. There are also reports on the associations
between increased levels of proinflammatory cytokines and ASD. Finally, infections in mothers during
pregnancy are linked to an increased risk of ASD.
Conclusion: We propose that the large inconsistencies in findings among studies in the field are due to
differences in subdiagnoses among the included children with ASD. Well-phenotyped ASD samples are
needed to understand the biological and immunological mechanisms underpinning ASD and its subdiagnoses.
Future research should apply new strategies to scrutinize the link between ASD and changes in
immune responsivity. Important new research avenues are to investigate the associations (a) between different
ASD phenotypes and aberrations in (auto)immune pathways and (b) between reduced natural regulatory
autoimmune responses during pregnancy, which are in turn associated with increased oxidative and
nitrosative stress in maternal blood and putative detrimental effects in the offspring.