The Role of the Immune System in Autism Spectrum Disorder

In the paper

“The postnatal environment, on the other hand, is characterized by related but distinct profiles of immune dysregulation, inflammation, and endogenous autoantibodies that all persist within the affected individual.”

In the paper

“genes implicated by large genome-wide studies have been shown to account for only a fraction of ASD diagnoses”

What the sources say

• Not checked yetcites Abrahams and Geschwind, 2008 source
• Not checked yetcites Badcock, 2011 source
• Not checked yetcites Happe et al, 2006 source

In the paper

“in the intervening years numerous other infections have been connected to the incidence of ASD”

In the paper

“During gestation, prenatal insults including maternal infection and subsequent immunological activation may increase the risk of autism in the child.”

In the paper

“research emerging within the past two decades suggests that immune dysfunction is a viable risk factor contributing to the neurodevelopmental deficits observed in autism spectrum disorders (ASD).”

In the paper

“mounting evidence for the ability of the immune system and abnormal immune function, including inflammation, cytokine dysregulation, and anti-brain autoantibodies, to act as a significant influence on ASD”

In the paper

“In a study utilizing banked mid-pregnancy (prospective) blood samples, the authors noted that maternal autoantibodies reactive to proteins near 37 and 73 kDa were only found in women whose children later received a diagnosis of ASD”

What the sources say

• Not checked yetcites Croen and Braunschweig, 2008a

In the paper

“There is strong evidence that disruption of normal cytokine levels has a significant role as a risk factor for several neurodevelopmental defects, including schizophrenia and autism”

What the sources say

• Not checked yetcites Boulanger and Shatz, 2004 source
• Not checked yetcites Brown et al, 2004b
• Not checked yetcites Deverman and Patterson, 2009 source

In the paper

“thus establishing a link between CRS and autism that has been supported by others”

What the sources say

• Not checked yetcites Deykin and MacMahon, 1979 source

In the paper

“attempting the poly(I:C) MIA model in IL-6 knockout mice showed no statistically significant differences in PPI or social behavior via the three-chamber test from untreated IL-6 knockouts”

In the paper

“The MIA model in its most common design involves challenging pregnant rodents via direct infection (eg, influenza, Escherichia coli) or the dsRNA mimic poly (I:C); significant immunological, neurodevelopmental, and behavioral changes are then observed in the offspring”

What the sources say

• Not checked yetcites Gilmore et al, 2005 source
• Not checked yetcites Meyer et al, 2005 source
• Not checked yetcites Urakubo et al, 2001 source

In the paper

“a study that examined serum from 11 mothers of young children and found six with circulating antibodies that targeted lymphocyte antigens of the children”

What the sources say

• Not checked yetcites Warren et al, 1990 source

In the paper

“Varying reports have also implicated measles and mumps (Deykin and MacMahon, 1979), cytomegalovirus (Libbey et al, 2005), polyomaviruses (Lintas et al, 2010), and influenza”

What the sources say

• Not checked yetcites Deykin and MacMahon, 1979 source
• Not checked yetcites Libbey et al, 2005 source
• Not checked yetcites Lintas et al, 2010 source

In the paper

“The implication is that the response to the infection, not just a few select pathogens, can lead to ASD in the offspring.”

In the paper

“autoantibodies to proteins that are a key to healthy neurodevelopment are also thought to be a viable pathogenic mechanism in a subset of cases”

In the paper

“the evidence presented thus far strongly suggests a connection between maternal infection and altered neurodevelopment”

In the paper

“Brimberg et al (2013) examined plasma from 2431 mothers of ASD children and compared it with plasma from 654 GP women, finding that mothers of children with ASD were four times as likely to have circulating anti-brain antibodies.”

What the sources say

• Not checked yetcites Brimberg et al, 2013 source

In the paper

“Most recently, studies have demonstrated that elevated mid-gestational levels of inflammatory cytokines and chemokines are more highly associated with the ASD subphentoype that presents with intellectual disability (ID), compared with ASD without ID, developmental delay (DD) without ASD, and typically developing controls (Jones et al, 2016).These included higher levels of GM-CSF, TNF-α, IFNγ, IL-1”

What the sources say

• Not checked yetcites Jones et al, 2016

In the paper

“The study reported 18 children with some degree of autism, implying an incidence of 741 cases per 10 000 among the population of CRS children”

• Also stated in: § Congenital Infection · plain

  “Chess followed-up as the children aged and found even higher rates of autism (905 per 10 000)”

What the sources say

• Not checked yetcites Chess, 1971 source
• Not checked yetcites Chess, 1977 source
• Not checked yetcites Chess, 1978 source

In the paper

“A more expansive study by Zerbo et al (2015) found that maternal infection diagnosed at a hospital admission, especially bacterial ones, correlated with increased risk of ASD.”

What the sources say

• Not checked yetcites Zerbo et al, 2015 source

In the paper

“it has now been demonstrated through animal models that merely an activated immune response in the mother, absent any infection, is sufficient to lead to changes in the offspring”

What the sources say

• Not checked yetcites Shi et al, 2003 source

In the paper

“Singer et al (2006) found that children with autism were more likely than their non-autistic siblings or controls to have serum that tested positive via western blot to fresh human brain samples (caudate, putamen, and prefrontal cortex).”

What the sources say

• Not checked yetcites Singer et al (2006) source

In the paper

“and among positive samples, those with ASD immunostained more strongly than controls (Mazur-Kolecka et al, 2014).”

What the sources say

• Not checked yetcites Mazur-Kolecka et al, 2014 source

In the paper

“Numerous studies have shown a connection between the members of the expansive family of HLA alleles and incidence of autism (Torres et al, 2012), in particular the class II DRB1.”

What the sources say

• Not checked yetcites Torres et al, 2012

In the paper

“when behavioral outcomes were characterized in the children of the 7% of mothers with a combined reactivity to LDH, STIP1, and CRMP1 (corresponding to the original 37/73 kDa band pattern) this pattern of reactivity correlated with an increase in stereotypic behaviors in the child”

What the sources say

• Not checked yetcites Braunschweig et al, 2013 source

In the paper

“The authors showed that 45 and 62 kDa antibodies in the children correlated with severity of autism, IQ, and impaired motor function and social interaction, as scored on the Vineland Adaptive Behavior Scales.”

What the sources say

• Not checked yetcites Piras et al, 2014 source

In the paper

“A larger 2011 study expanded on these findings, testing plasma from a cohort of 277 children with ASD and 189 TD controls for reactivity to human and macaque cerebellar protein medleys, with ASD children more likely to test positive for anti-brain autoantibodies via western blotting (Goines et al, 2011a).”

What the sources say

• Not checked yetcites Goines et al, 2011a

In the paper

“The hypervariable region 3 of DRB1*0401 has been associated with an increased relative risk for autism in children from Utah (Warren et al, 1996).”

What the sources say

• Not checked yetcites Warren et al, 1996 source

In the paper

“Studies by Braunschweig et al (2013) utilized two-dimensional gel electrophoresis followed by tandem mass spectrometry peptide sequencing to identify seven developmentally regulated proteins in the fetal brain that are recognized by maternal autoantibodies.These are lactate dehydrogenase A and B (LDH-A and LDH-B), stress-induced phosphoprotein 1 (STIP1), collapsin response mediator proteins 1 and”

What the sources say

• Not checked yetcites Braunschweig et al, 2013 source

In the paper

“the presence of such antibodies was higher in severe diagnoses (87.5%) than mild/ moderate diagnoses (25%)”

What the sources say

• Not checked yetcites Mostafa and Al-Ayadhi (2012) source

In the paper

“When a subset of subject samples was examined via immunohistochemistry (IHC), 21% of those from children with ASD had 'intense immunoreactivity' while none of the TD controls exhibited such reactivity.”

What the sources say

• Not checked yetcites Wills et al, 2009 source

In the paper

“A similar result found that children with autism showed positive serum anti-brain reactivity against prenatal rat proteins by western blot, with a different set of banding patterns relative to their non-autistic siblings and other controls (Zimmerman et al, 2007).”

What the sources say

• Not checked yetcites Zimmerman et al, 2007 source

In the paper

“After birth and at least throughout childhood, an individual with ASD may have endogenous anti-brain autoantibodies, separate from any maternal IgG, which correlate with aberrant behaviors and impaired development.”

What the sources say

• Not checked yetcites Piras et al, 2014 source

In the paper

“numerous studies have reported the presence of circulating anti-brain immunoglobulins in patients with ASD, as well as related conditions such as multiple sclerosis (Ryberg, 1982), schizophrenia (Henneberg et al, 1994), and systemic lupus erythematosus (SLE) (Libbey and Fujinami, 2010;Mackay et al, 2015;Suurmond and Diamond, 2015).”

What the sources say

• Not checked yetcites Ryberg, 1982 source
• Not checked yetcites Henneberg et al, 1994 source
• Not checked yetcites Libbey and Fujinami, 2010 source

In the paper

“showing that while correlations between the two discrete autoantibody populations do exist, maternal-and child-borne autoantibodies each retain their own distinct and defining characteristics.”

What the sources say

• Not checked yetcites Piras et al, 2014 source

In the paper

“Braunschweig et al (2012b) performed a similar study to demonstrate atypical anxiety and sociality alongside impaired motor and sensory abilities following a single intravenous injection.”

What the sources say

• Not checked yetcites Braunschweig et al, 2012b

In the paper

“children born to mothers with this pattern of autoantibody binding also exhibited higher total cerebral volume when compared both to children with ASD born to autoantibody-negative mothers as well as typically developing control children”

What the sources say

• Not checked yetcites Nordahl et al, 2013 source

In the paper

“An examination of anti-brain autoantibodies in a cohort of 355 Italian children with autism and their mothers and unaffected siblings found that autoantibodies in autistic individuals correlated with increased severity, stereotypies, and cognitive impairment (Piras et al, 2014).”

What the sources say

• Not checked yetcites Piras et al, 2014 source

In the paper

“A 2009 study of plasma from 63 young children with ASD found that 21% of them had antibodies positive against both human and macaque cerebellum samples via western blot, while only one out of the 63 typical developing (TD) controls (2%) tested positive (Wills et al, 2009).”

What the sources say

• Not checked yetcites Wills et al, 2009 source

In the paper

“children may have their own, endogenous antibrain autoantibodies that are connected with atypical development, distinct from the previously described maternal autoantibodies.”

In the paper

“as well as in females (90%) compared with males (53.3%).”

What the sources say

• Not checked yetcites Mostafa and Al-Ayadhi (2012) source

In the paper

“Mostafa and Al-Ayadhi (2012), who found a higher rate of anti-neuronal antibodies in a cohort of 80 Saudi children with ASD vs 80 -GP controls, as tested via immunofluorescence against monkey cerebellum (62.5 vs 5%)”

What the sources say

• Not checked yetcites Mostafa and Al-Ayadhi (2012) source

In the paper

“DRB1 was also associated with autism in Han Chinese (Chien et al, 2012), Egyptian (Mostafa et al, 2013), and Saudi populations (Al-Hakbany et al, 2014).”

What the sources say

• Not checked yetcites Chien et al, 2012 source
• Not checked yetcites Mostafa et al, 2013 source
• Not checked yetcites Al-Hakbany et al, 2014

In the paper

“A later study found autoimmunoreactivity to neuronal progenitor cells (NPCs) to be far more common in children with autism than controls”

What the sources say

• Not checked yetcites Mazur-Kolecka et al, 2014 source

In the paper

“it seems evident that maternal autoantibodies appear to influence, if not define, a specific subset of ASD.”

In the paper

“The authors then showed that unstimulated NK cells-specifically the CD56 dim subset-stained positive for perforin, granzyme B, and IFN-γ at higher frequencies in ASD patients as compared with general population (GP) controls.”

What the sources say

• Not checked yetcites Enstrom et al, 2009b

In the paper

“Another 2008 study identified 11 genes that were differentially expressed in children with autism, as well as within the subsets of early onset and developmental regression, as compared with the general population (overexpression in autism samples were confirmed for seven of 11 via qPCR) (Gregg et al, 2008).”

What the sources say

• Not checked yetcites Gregg et al, 2008 source

In the paper

“A more recent report noted a decrease in CD4 + CD25 high regulatory T cells in children with autism (Mostafa et al, 2010).”

What the sources say

• Not checked yetcites Mostafa et al, 2010 source

In the paper

“as did an examination of neuroinflammation in brains from individuals with autism (Vargas et al, 2005).”

What the sources say

• Not checked yetcites Vargas et al, 2005 source

In the paper

“When Lintas et al (2012) reviewed several genome-wide expression studies in 2012 (including the two just mentioned), they found a strong connection to the immune system; of the 464 genes identified, six out of the top 10 KEGG ontology pathways were functions of the immune systems.”

What the sources say

• Not checked yetcites Lintas et al (2012) source

In the paper

“while a supporting 1990 study suggested CD4 + cell levels were decreased in autism (Yonk et al, 1990).”

What the sources say

• Not checked yetcites Yonk et al, 1990 source

In the paper

“A 2014 RNA-seq study built upon this concept with a gene ontology analysis showing that the autism transcriptome was heavily enriched for immune response genes (Gupta et al, 2014).”

What the sources say

• Not checked yetcites Gupta et al, 2014 source

In the paper

“They describe a model whereby a significantly altered neuroimmune milieu persists in constant dysregulation.”

What the sources say

• Not checked yetcites Voineagu et al, 2011 source

In the paper

“The authors also defined a module of genes upregulated in ASD that was enriched for astrocytes and activated microglia.”

What the sources say

• Not checked yetcites Voineagu et al, 2011 source

In the paper

“the larger picture is one of a cascading network of genetic interactions that leads to ongoing, persistent immune imbalance.”

In the paper

“Interestingly, Guerini et al (2015) discovered a 14-basepair insertion in HLA-G that was found more often in individuals with ASD and their mothers.”

What the sources say

• Not checked yetcites Guerini et al (2015) source

In the paper

“Voineagu, et al, examined gene expression in ASD and control brains, and as expected found hundreds of genes that were differentially expressed (Voineagu et al, 2011).”

What the sources say

• Not checked yetcites Voineagu et al, 2011 source

In the paper

“These immune-relevant gene sets fell into six classes: antigenspecific immune response, inflammation, cell death, autoimmune diseases, migration, and the natural killer T cell pathway.”

What the sources say

• Not checked yetcites Garbett et al, 2008 source

In the paper

“A more recent study of NK cells recapitulates the genetic changes previously alluded to, showing that NK cells in children with autism had higher expression of NK cytotoxicity genes (Enstrom et al, 2009b).”

What the sources say

• Not checked yetcites Enstrom et al, 2009b

In the paper

“the authors found 31 sets of genes that were differentially expressed between autistic and control samples; of these, 19 were connected to the immune system.”

What the sources say

• Not checked yetcites Garbett et al, 2008 source

In the paper

“Linkage studies by Campbell et al (2006), have found an association between ASD and a single SNP (rs1858830) in the promoter of MET.”

What the sources say

• Not checked yetcites Campbell et al (2006) source

In the paper

“Enstrom et al (2010) showed that cultured monocytes from ASD patients responded differently to TLR stimulation”

What the sources say

• Not checked yetcites Enstrom et al (2010) source

In the paper

“Interestingly, upon stimulation, NK cells showed much lower staining to these same targets as compared with GP.”

What the sources say

• Not checked yetcites Enstrom et al, 2009b

In the paper

“A 2008 study explored transcriptomic changes in the temporal cortex of children and adults with autism, finding 152 transcripts with varied expression, 130 of which were upregulated (Garbett et al, 2008).”

What the sources say

• Not checked yetcites Garbett et al, 2008 source

In the paper

“Immune dysregulation was a common trend in genomic studies, particularly in the NK cell and cytokine pathways.”

What the sources say

• Not checked yetcites Lintas et al (2012) source

In the paper

“Ashwood et al (2011b) demonstrated a differential response by PHA-stimulated peripheral blood mononuclear cells (PBMCs), including reduced numbers of CD134-and CD25-activated CD3 + , CD4 + , and CD8 + T cells.”

What the sources say

• Not checked yetcites Ashwood et al (2011b)

In the paper

“The authors also found considerable levels of immune dysregulation, observing significantly more CD56 + NK cells in children with ASD compared with controls.”

What the sources say

• Not checked yetcites Enstrom et al, 2009b

In the paper

“A previously mentioned mouse model also implicated T cell skewing in ASD-relevant behavioral deficits (Ponzio et al, 2007)”

What the sources say

• Not checked yetcites Ponzio et al, 2007 source

In the paper

“A reduction in NK cell activity was shown in teenage and adult autism patients, with 12 out of 31 patients showing lower activity in PBMCs via K562 chromium-release assays (Warren et al, 1987).”

What the sources say

• Not checked yetcites Warren et al, 1987 source

In the paper

“The genes significantly upregulated in ASD were heavily enriched for immune and inflammatory response functions, immunoglobulin domains, and other immune-regulatory ontologies.”

What the sources say

• Not checked yetcites Voineagu et al, 2011 source

In the paper

“The authors suggest that immune system genes may function as a fundamental convergence for autistic disorders.”

What the sources say

• Not checked yetcites Ziats and Rennert (2011) source

In the paper

“Taken together, the genetic forces noted in both children and adults with autism are myriad, but insufficiently explanatory.”

In the paper

“the apparent shift in subclass to IgG4 means that children with autism are likely to have a higher percentage of circulating IgG with an inherently lower affinity for the antibody receptors on leukocytes (Enstrom et al, 2009a;Zaman et al, 2016).”

What the sources say

• Not checked yetcites Enstrom et al, 2009a
• Not checked yetcites Zaman et al, 2016 source

In the paper

“A 2006 study showed increases in the anti-inflammatory Th2 cytokines IL-4, IL-5, and IL-13 from PHA-stimulated PBMCs (Molloy et al, 2006)”

What the sources say

• Not checked yetcites Molloy et al, 2006 source

In the paper

“A 2012 follow-up study ruled out abnormal B-cell function as the source of aberrant IgG levels (Heuer et al, 2012).”

What the sources say

• Not checked yetcites Heuer et al, 2012 source

In the paper

“Vargas et al (2005) likewise showed the presence of an active neuroinflammatory environment, finding higher levels of MCP-1, TGF-β, and IL-6 in the brains of autistic patients.”

What the sources say

• Not checked yetcites Vargas et al (2005) source

In the paper

“while a mouse model in 2007 showed Th1-skewed T-cell development in amniotic fluid alongside stereotypies in the offspring following treatment of pregnant dams with IL-2 (Ponzio et al, 2007).”

What the sources say

• Not checked yetcites Ponzio et al, 2007 source

In the paper

“Although an increased pro-inflammatory environment seems well supported (Haroon et al, 2012)”

What the sources say

• Not checked yetcites Haroon et al, 2012 source

In the paper

“Examining children from the same cohort, the authors also published on increased levels of the chemokines MCP-1, RANTES, and eotaxin (Ashwood et al, 2011c).”

What the sources say

• Not checked yetcites Ashwood et al, 2011c

In the paper

“a 2002 study demonstrated an increase in the blood cytokines IL-1RA and IFN-γ, suggesting a more Th1-like, proinflammatory response (Croonenberghs et al, 2002a)”

What the sources say

• Not checked yetcites Croonenberghs et al, 2002a

In the paper

“In both studies, increased cytokine or chemokine levels were correlated with increased aberrant behavior and impaired development (Ashwood et al, 2011a(Ashwood et al, , 2011c)).”

What the sources say

• Not checked yetcites Ashwood et al, 2011a
• Not checked yetcites Ashwood et al, 2011c

In the paper

“Siniscalco et al (2016) examined 104 children with ASD, and found significantly lower, atypical levels of CD57 + NK cells as compared with both age-matched and adult controls.”

What the sources say

• Not checked yetcites Siniscalco et al, 2016

In the paper

“In contrast to most of the above studies, a 2012 report using dried blood samples suggested that children with ASD had lower levels of both Th1-like and Th2-like cytokines (Abdallah et al, 2012b).”

What the sources say

• Not checked yetcites Abdallah et al, 2012b

In the paper

“Of particular note is that many of the above studies found no increase in the Th2 cytokine IL-10 (Croonenberghs et al, 2002a;Krakowiak et al, 2015;Li et al, 2009;Molloy et al, 2006).”

What the sources say

• Not checked yetcites Croonenberghs et al, 2002a
• Not checked yetcites Krakowiak et al, 2015
• Not checked yetcites Li et al, 2009

In the paper

“Offending antibodies of either origin appear to persist systemically for extended periods of time (Mostafa and Al-Ayadhi, 2012;Piras et al, 2014;Singer et al, 2006;Zimmerman et al, 2007)”

What the sources say

• Not checked yetcites Mostafa and Al-Ayadhi, 2012 source
• Not checked yetcites Piras et al, 2014 source
• Not checked yetcites Singer et al, 2006 source

In the paper

“A large 2011 study of children with ASD found an increase in plasma levels of a broad range of cytokines, including the Th1-like IL-12p40 and pro-inflammatory cytokines IL-1β, IL-6, IL-8, and GM-CSF (Ashwood et al, 2011a).”

What the sources say

• Not checked yetcites Ashwood et al, 2011a

In the paper

“A later study with children from the same cohort found increased plasma levels of the weakly active IgG4 subclass among ASD patients (Enstrom et al, 2009a), as did an earlier study comparing ASD children to their siblings (Trajkovski et al, 2004).”

What the sources say

• Not checked yetcites Enstrom et al, 2009a
• Not checked yetcites Trajkovski et al, 2004

In the paper

“Given the ability of the immune environment to affect behavior (Filiano et al, 2016)”

What the sources say

• Not checked yetcites Filiano et al, 2016 source

In the paper

“Although reports indicate the presence of these antibodies may correlate with adverse conditions in the patients (Braunschweig et al, 2012a;Goines et al, 2011a;Mostafa and Al-Ayadhi, 2012;Piras et al, 2014)”

What the sources say

• Not checked yetcites Braunschweig et al, 2012a
• Not checked yetcites Goines et al, 2011a
• Not checked yetcites Mostafa and Al-Ayadhi, 2012 source

In the paper

“After birth and at least throughout childhood, an individual with ASD may have endogenous anti-brain autoantibodies, separate from any maternal IgG, which correlate with aberrant behaviors and impaired development.”

In the paper

“There also exists a broad picture of ASD-related immune dysregulation, including an increased inflammatory cytokine milieu (eg, IL-6, IL-8, and MCP-1), thus leading to an increased, pro-inflammatory Th1/Th2 ratio.”

In the paper

“T-cell and NK-cell populations may also be skewed, displaying a shift in cell subpopulations.”

In the paper

“There also exists a broad picture of ASD-related immune dysregulation, including an increased inflammatory cytokine milieu (eg, IL-6, IL-8, and MCP-1), thus leading to an increased, pro-inflammatory Th1/Th2 ratio.”

In the paper

“After birth and at least throughout childhood, an individual with ASD may have endogenous anti-brain autoantibodies, separate from any maternal IgG, which correlate with aberrant behaviors and impaired development.”

In the paper

“NK cells in particular show an increased baseline activity but a decreased response to activation, rendering the cells unable to properly respond to stimuli.”

In the paper

“After birth and at least throughout childhood, an individual with ASD may have endogenous anti-brain autoantibodies, separate from any maternal IgG, which correlate with aberrant behaviors and impaired development.”

In the paper

“alongside direct genetic evidence that links ASD and schizophrenia (Cantor and Geschwind, 2008;Ellis et al, 2016;Zhou et al, 2016).”

What the sources say

• Not checked yetcites Cantor and Geschwind, 2008 source
• Not checked yetcites Ellis et al, 2016 source
• Not checked yetcites Zhou et al, 2016 source

In the paper

“NK cells in particular show an increased baseline activity but a decreased response to activation, rendering the cells unable to properly respond to stimuli.”

In the paper

“T-cell and NK-cell populations may also be skewed, displaying a shift in cell subpopulations.”

In the paper

“Autoantibodies, such as those described above, have been found in patients of other autoimmune disorders, including multiple sclerosis (Ryberg, 1982), schizophrenia (Henneberg et al, 1994), and SLE (Libbey and Fujinami, 2010).”

What the sources say

• Not checked yetcites Ryberg, 1982 source
• Not checked yetcites Henneberg et al, 1994 source
• Not checked yetcites Libbey and Fujinami, 2010 source

In the paper

“Other genetic factors include the oncogene MET and members of the diverse family of HLA genes.”

In the paper

“Further lending credence to this association are numerous studies showing that a significant risk factor for autism is a family history of autoimmune disease (Brimberg et al, 2013;Gesundheit et al, 2013;Gottfried et al, 2015;Wu et al, 2015)”

What the sources say

• Not checked yetcites Brimberg et al, 2013 source
• Not checked yetcites Gesundheit et al, 2013 source
• Not checked yetcites Gottfried et al, 2015 source

In the paper

“including a 2015 study that found a more than double risk of ASD in children of mothers with SLE than those of controls (Vinet et al, 2015).”

What the sources say

• Not checked yetcites Vinet et al, 2015 source

In the paper

“The broader background of immunogenetic factors of ASD includes multiple networks of the immune system, such as pathways that regulate cytokines and NK cells, which together constitute a broad, endogenous environment of atypical immune regulation and response.”

In the paper

“Despite the differences between these two disorders, the similarities between them are such that results from animal models like the MIA model may be overlapping and confounded (Bauman et al, 2014;Young et al, 2016).”

What the sources say

• Not checked yetcites Bauman et al, 2014 source
• Not checked yetcites Young et al, 2016 source

In the paper

“The broader background of immunogenetic factors of ASD includes multiple networks of the immune system, such as pathways that regulate cytokines and NK cells, which together constitute a broad, endogenous environment of atypical immune regulation and response.”

In the paper

“Ongoing immune dysregulation persists in autism.”

In the paper

“NK cells in particular show an increased baseline activity but a decreased response to activation, rendering the cells unable to properly respond to stimuli.”

In the paper

“In the prenatal environment, a strong line of evidence is beginning to develop in support of maternal immune dysregulation as it affects neurodevelopment based on studies on maternal infection, immune activation, and maternal autoantibodies directed toward the developing fetal brain.”