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One of the most prominent findings in those with autism is a dysregulated immune system which may predispose them to infections, chronic inflammation and increased autoimmune reactions. Some studies indicate that immune abnormalities are estimated to be present in up to 70% of patients with autism. 

 

Various studies have confirmed implications of pro-inflammatory cytokinesactivated microglia, both lowered and increased immunoglobulins, persistent infections, reduced natural killer cells,

and other pathologies related to the immune system. Some studies have indicated an imbalance between a Th1 to a Th2 immune response.

 

A subset of individuals with autism have a history of frequent upper respiratory infections, otitis media, atopic dermatitis, fungal infections, viruses, and may have regressed after a viral illness, immunization, or infection. Many harbor chronic co-infections, such as human herpes virus, lyme, cytomegalovirus, or mycoplasma. This sub-cohort should be evaluated for a Primary Immune Deficiency.

 

Some parents report an improvement in their child's autism symptoms during a fever. There is also a growing body of research which establishes a link between maternal immune activation during pregnancy and autism.

Additionally, some studies indicate a subset of individuals have brain autoantibodies. There is a strong correlation of family history of autoimmunity, especially in mothers of those with ASD.

 

Another cohort may be diagnosed with Pediatric Autoimmune Neurological Disorder Associated with Streptococcus (PANDAS) or Pediatric Autoimmune Neurological Syndrome (PANS)

Parents also report a worsening of their child's autism symptoms when they are exposed to allergens and have an increased histamine response; this may indicate a Mast Cell Activation Disorder (MCAD). Mast cell disorders can have varying symptoms, including, but not limited to: nausea, vomiting, anaphylaxis, cutaneous reactions, vertigo, headaches, and psychiatric or behavioral symptoms.

 

Many parents report a reduction in symptoms of autism after removing certain foods, additives and pesticides from their child's diet, or adopting a ketogenic based diet, this may be due to increased dietary allergies.

 

The immune system is complicated, and research in this area is continually emerging.

Please see selected studies below; much more can be found at PubMed.

An individual with autism who presents with tics, OCD, severe food restriction, emotional lability, depression, anxiety, oppositional behaviors or a deterioration in behavior, motor functioning, or incontinence should be evaluated for PANDAS or PANS.

Click here for diagnostic guidelines.      

Click here to learn more about labs.

Clinical Evaluation of Youth with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): Recommendations from the 2013 PANS Consensus Conference

For those with suspected immune dysfunction, please click here for more specific information of the various types of immune deficiency disorders. In some cases replacement immunoglobulin therapy may be indicated. For more information on primary immune deficiency, please click here.

Primary Immune Deficiency Treatment Consortium (PIDTC) report

Extensive alterations in immune function have now been described in both children and adults with ASD, including ongoing inflammation in brain specimens, elevated pro-inflammatory cytokine profiles in the CSF and blood, increased presence of brain-specific auto-antibodies and altered immune cell function. Furthermore, these dysfunctional immune responses are associated with increased impairments in behaviors characteristic of core features of ASD, in particular, deficits in social interactions and communication. This accumulating evidence suggests that immune processes play a key role in the pathophysiology of ASD...

The collective findings of immune aberration in ASD, and the effects of immune dysfunction in normal neurodevelopment, are difficult to ignore. Despite several early challenges the evidence of immune cell dysfunction in ASD has continued to grow. In conjunction, recent basic research has provided further evidence of how the immune system can profoundly impact neurodevelopment, cognitive function, and behavior. The dysfunctional immune activity observed in ASD spans both innate and adaptive arms of the immune system, and suggest perturbations in either area may have profound effects on neurodevelopment. Cytokines that have been observed at atypical levels in ASD, including the brain tissue, CSF, circulating blood, and GI tissues, can alter neuronal survival and proliferation. Similarly, cellular dysfunction observed in ASD may contribute to atypical CNS function in a number of ways including the production of cytokines, abnormal cell lysis and generation of brain-reactive antibodies. Abnormal levels of complement proteins and linkage to specific MHC molecules, have been repeatedly observed as in ASD, and may suggest that a role for immune function in synaptic pruning/plasticity in ASD.

The underlying cause of immune abnormalities in ASD may extend from genetic to maternal immune activation, or any number of unknown causes. 

Onore C, Careaga M, Ashwood P. The role of immune dysfunction in the pathophysiology of autism. Brain, behavior, and immunity. 2012;26(3):383-392. doi:10.1016/j.bbi.2011.08.007.

Immune Laboratory Considerations

*Complete Blood Count (CBC) with differential                       *See links above for detailed labs for PANS,

*IgE Food and Environmental Allergens.                                    PANDAS, Cunningham Panel, CVID,

*IgG ELISA (foods, respiratory inhalants).                                  Specific Antibody Deficiency and Mast Cell

*Total immunoglobulins with IgG subclasses                              Disorders

*Natural Killer Cells, Functional 

*Absolute Lymphocytes and Natural Killer Cells (CD3-CD56+CD16+)

*Neopterin, Serum

*T Lymphocyte Panel

*T and B cells total

*Thyroid Panel with TSH

*Anti-Streptolysin O Antibody (ASO) 

*AntiDNase Antibody

*Urinalysis Complete

*HHV 6 Antibodies 

*GAD65 Autoantibody Test

*C-Reactive Protein (CRP)

*Vaccine Titers

*Viral Antibodies (EBV, CMV, Influenza, Varicella)

*Streptococcus pneumoniae Antibody (IgG)

*Sedimentation rate

*ANA screen

*25-hydroxyvitamin D

* B1 (thiamine or thiamin); B2 (riboflavin); B3 (niacin); B5 (pantothenic acid); B6 (pyridoxal phosphate); B7 (biotin), B12 (methylcobalamin)

* Vitamin A

*Trace Minerals

A dysregulated immune system leads to: 

Deficiency (inadequate immune response to virus, infection or normal function)

Allergy (hyperactive response to environmental stimuli)

Autoimmunity (abnormal response to self, may be chronic and systemic)

Inflammation, neuroinflammation 

Selected Studies

"In ASD there is evidence for increased type-2 cytokines, microglia activation, M2A polarization, and increased levels of growth factors. In neurons, these growth factors drive a signal transduction pathway that leads to activation of the enzyme mammalian Target of Rapamycin (mTOR), and thereby to the inhibition of autophagy. Activation of mTOR is an effect that is also common to several of the genetic forms of autism. In the central nervous system, redundant synapses are removed via an autophagic process. Activation of mTOR would diminish the pruning of redundant synapses, which in the context of ASD is likely to be undesired. Based on this line of reasoning, atopic diseases like food allergy, eczema or asthma would represent risk factors for autism spectrum disorders."

Kalkman, Hans O., and Dominik Feuerbach. “Microglia M2A Polarization as Potential Link between Food Allergy and Autism Spectrum Disorders.” Pharmaceuticals 10.4 (2017): 95. PMC.

"This evidence for abnormal cytokine profiles in ASD suggests that immune system disturbances may be active and continuous contributors to the presentation of ASD. It is this accumulation of evidence that has acted as the catalyst for efforts to characterize possible subgroups of ASD patients who present with immune system abnormalities or dysfunction and altered patterns of symptom presentation...Overall, these relationships between immune dysfunction and behavioral symptoms associated with an ASD presentation suggest an ongoing relationship impacting the severity of the condition in children with an ASD diagnosis."

Masi, Glozier, Dale, Guastella; The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder; Neurosci. Bull. April, 2017, 33(2):194–204

"In summary, 70% of the analyzed patients with autism had CD57+CD3– counts below the normal range...In summary, our data suggest that CD57+CD3– NK cells may play a role in the pathophysiology of autism. Lower levels of CD57+ NK cells may reflect an immunopathological foundation for the creation and/or maintenance of autism, with a possible link to the ASD subgroup characterized by chronic infection."

Siniscalco, et al; 

Decreased Numbers of CD57+CD3− Cells Identify Potential Innate Immune Differences in Patients with Autism Spectrum Disorder

In Vivo March-April 2016 30 (2) 83-89

"Despite the dogma that peripheral immune responses could not affect central nervous system (CNS) function under normal circumstances, substantial evidence over the past 10 years suggests that immune-CNS cross-talk may be the norm rather than the exception. Thus, peripheral immune cells can alter cognition in the absence of CNS immune cell infiltration, suggesting that neural-immune cross-talk may involve more than the simple “breaching” of the blood brain barrier (BBB). Multiple members of the large family of cytokines are normally produced in the healthy brain where they play critical roles in almost every aspect of neural development, including neurogenesis, migration, differentiation, synapse formation, plasticity, and responses to injury [26,27]. As such, the early cytokine alteration influencing the brain function may identify the onset of developmental disorders like autism as well as underline a particular pattern of disease progression or severity [28,29,30].

Multiples papers reporting immune changes in autism were based on cytokine analysis [31,32,33,34,35,36,37]. In the last five years, more than 700 published articles have reported differential patterns of cytokine and other mediators in fluids and brain tissue of individuals with ASD (data taken from PubMed Central, August 2016), nevertheless there has not been a consensus on the contribution of cytokine to clinical behavioral outcome and comorbidities [38,39].

Changes to plasma cytokine levels in individuals with ASD have provided evidence of immune dysfunction associated with or without

an impaired behavioral outcome."

Inga Jácome MC, Morales Chacòn LM, Vera Cuesta H, et al. Peripheral Inflammatory Markers Contributing to Comorbidities in Autism. Robledo J, ed. Behavioral Sciences. 2016;6(4):29. doi:10.3390/bs6040029.

"Recent studies have shown strong associations between allergies, asthma, autoimmune diseases and psoriasis in the mother with increased risk for ASD in their children. Moreover, mothers with mastocytosis or MC activation syndrome were much more likely to have children who developed ASD. Allergies and auto-immune diseases have been increasing significantly. Early reports indicated more frequent allergies in ASD children, with food allergies being the most prevalent complaint, often in the absence of elevated serum IgE or positive skin tests. A large epidemiological study of noninstitutionalized children (n=92642; 0–17 years old) showed that eczema was strongly associated with ASD and attention deficit hyperactivity disorder...Most children with ASD are often prescribed psychotropic medications, primarily risperidone and aripiprazole to reduce disruptive and aggressive behaviors, but these drugs have no effect on the core symptoms of ASD."

Theoharides, Tsilioni, Patel, Doyle; Atopic diseases and inflammation of the brain in the pathogenesis of autism spectrum disorders; Transl Psychiatry (2016) 6, e844; doi:10.1038/tp.2016.77

"Taking together, these studies suggest that SCFAs affect the activation and effector function of T cells. However, despite the fact that most of the studies support the idea that SCFAs induce a tolerogenic and anti-inflammatory profile of T cells,  

evidences also indicate that under some conditions they may induce Th1 and Th17 

responses, and, depending on the disease/model and other factors including time, route and concentrations of treatment used, they can both ameliorate or worsen the disease severity.51,52,58,60...The interaction between microbiota and immune system is bidirectional and involves different components/mechanisms, which are beginning to be identified and understood in physiological and pathological states. SCFAs, as described in this review, are an important link between microbiota and immune system." 

Correa, R, et al. "Regulation of immune cell function by short-chain fatty acids" Clinical & Translational Immunology"(2016) 5, e73; doi:10.1038/cti.2016.17; nature.com

"In addition, reported food allergies were significantly associated with ASD (adjusted odds ratio = 2.23, 95% confidence interval 1.28, 3.89). Our results suggest food allergies and sensitivities may be more common in children with ASD, and that these issues may correlate with other behaviors." 

Lyall, K., Van de Water, J., Ashwood, P. and Hertz-Picciotto, I. (2015), Asthma and Allergies in Children With Autism Spectrum Disorders: Results From the CHARGE Study. Autism Research, 8: 567–574. 

"Consequently, we postulated that low peripheral blood iNKT numbers could reflect recruitment to the site of active eosinophilic inflammation. Hence, we analyzed the iNKT levels via Flow cytometry in esophageal biopsies from children with EoE –A and EoE-C. For the first time we described that iNKTs were significantly higher in esophageal biopsies obtained from children with EoE-A compared to those with EoE-C (p<0.05) (Figure 3). Peripheral blood iNKT levels were inversely related to iNKT levels in tissue samples suggesting that iNKTs may play a role in the pathogenesis of EoE by being recruited at the level of eosinophilic inflammation...This study suggests that sphingolipids (SLs) contained in milk may drive the development of EoE by promoting an iNKT-cell-mediated Th2-type cytokine response that facilitates eosinophil-mediated allergic inflammation."

S. Jyonouchi, C. L. Smith, F. Saretta, V. Abraham, K. R. Ruymann, P. Modayur-Chandramouleeswaran, M. -L. Wang, J. M. Spergel and A. Cianferoni, Invariant natural killer T cells in children with eosinophilic esophagitis. Clinical & Experimental Allergy, 2014 (44) 58–68.

"Behavioral symptoms, per parental reports, would typically ‘flare’ for a prolonged period following immune insults in ASD-IS children, despite resolution of acute physical symptoms such as fever or other signs of acute inflammation. When these results were compared to baseline data obtained during ‘non- flare’ states, we found significantly higher scores in subdomains I (irritability), II (lethargy), and IV (hyperactivity) in ABC scores (Table 3 and Figure 1) during ‘flares’ in ASD- IS children. These findings support parental impression of worsening behavioral symptoms in the ‘flare’ state following immune insults. In the ASD-IS children, ABC scores were assessed after resolution of acute symptoms of immune insults such as upper respiratory infection. Therefore, it is unlikely that behavioral changes are solely attributed to the pain and/or discomfort associated with acute illnesses."

Jyonouchi et al.: Cytokine profiles by peripheral blood monocytes are associated with changes in behavioral symptoms following immune insults in a subset of ASD subjects: an inflammatory subtype? Journal of Neuroinflammation 2014 11:187.

"Cytokines are intricately involved in neurodevelopment and neuronal function, and an ill-timed cytokine disruption can have long term neurological consequences. Further, cytokine expression is largely dependent on genetic and environmental influences. Therefore, they may represent a biomarker for genetic or environmental factors at play in autism. To illustrate the connection between immunity, genes, the environment, and neurodevelopmental outcome, consider two scenarios: First, an individual may be genetically poised to mount an inappropriate immune response to an infectious or toxic exposure. This individual might respond either too robustly or too weakly to resolve the threat without collateral damage to the brain and other body systems (including the immune system). Second, an individual may lack appropriate genetic machinery to excrete toxins; leading to their accumulation in tissue. This could lead to an amplification of the toxin’s effects on a variety of body systems, including the brain and immune system. For each child, an environmental challenge during a critical window of development could have especially severe consequences, causing abnormal CNS function, altered immune phenotypes, and perhaps autism. These scenarios represent an emerging global view of autism that considers a broad contribution of several factors, including genes, the environment, and the immune system."

Goines PE, Ashwood P. Cytokine dysregulation in autism spectrum disorders (ASD): Possible role of the environment. Neurotoxicology and teratology. 2013;36:67-81. doi:10.1016/j.ntt.2012.07.006.

"When innate immune responses were assessed, by measuring responses to a panel of TLR agonists, we observed significant differences in the ASD/SPAD children, as compared to control groups. That is, PBMCs from the ASD/ SPAD children tended to produce less pro-inflammatory cytokines (TNF-a, IL-1ß, IL-6, IL-12, and IL-23). Changes were most evident in the production of IL-6. As for production of counter-regulatory cytokines, PBMCs from ASD/SPAD children revealed less spontaneous IL-10 production than normal controls. Responses to TLR agonists in the non-ASD/SPAD children differed significantly from those observed in the ASD/SPAD children as detailed in the results section and Figure 1. Only common feature found in both the ASD/SPAD and non-ASD/SPAD children was lower spontaneous production of IL-10 than normal controls (Figure 1-C)."

Jyonouchi et al.: Immunological characterization and transcription profiling of peripheral blood (PB) monocytes in children with autism spectrum disorders (ASD) and specific polysaccharide antibody deficiency (SPAD): case study. Journal of Neuroinflammation 2012 9:4. 

"Regardless of the ontogeny of autism-associated maternal antibodies, there is a general consensus that the resulting pathogenic mechanism likely proceeds through 1 of 3 established mechanisms: (1) blockade or interference with the function of the target molecules22; (2) acting as an agonist and activating a receptor or signaling cascade23; or (3) through the induction of inflammation

and the consequent effects on CNS development." 

Braunschweig and Van De Water; Maternal Autoantibodies in Autism; Arch Neurol. 2012 June ; 69(6): 693–699. doi:10.1001/archneurol.2011.2506.

"Collectively, these data reveal a trend towards pro-inflammatory immune activity and away from regulatory measures in ASD. As many of the cytokines have profound effects on neuronal development, migration, differentiation and synapse formation (see below), a disrupted balance in the cytokine milieu may directly influence neurodevelopment, early brain development and alter behavior. To this end it is of note that the shift in cytokine balance in ASD is associated with greater impairments in key autism behavioral domains including social interaction and communication, as well as associated features such as aberrant behaviors (Table 1)."

Onore, Charity & Careaga, Milo & Ashwood, Paul. (2011). The role of immune dysfunction in the pathophysiology of autism. Brain, Behavior, and Immunity, 26(3), 383-392. Brain, behavior, and immunity. 26. 383-92. 10.1016/j.bbi.2011.08.007. 

"In summary, using a large number of participants from a population based case-control study, we demonstrate that there are significant increases in plasma IL-1β, IL-6, IL-8 and IL-12p40 levels in young children who have confirmed ASD as compared with confirmed and age-matched typically developing children. These levels were predominantly driven by increases in cytokines in CHARGE study children who experienced loss of language or social skills. Furthermore, elevations in these cytokine levels were associated with greater severity in the core domains of ASD and with greater impairments in aberrant behaviors. These findings suggest that ongoing inflammatory responses may be linked to disturbances in behavior, a conjecture that requires confirmation in a larger study, and most critically, in longitudinal investigations of the changes in cytokine levels prior to the diagnosis or development of ASD symptoms and over the natural history of the disorder."

Ashwood, et al; Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome; Brain Behav Immun. 2011 January ; 25(1): 40–45. doi:10.1016/j.bbi.2010.08.003

"Published findings have identified widespread changes in the immune systems of children with autism, at both systemic and cellular levels. Brain specimens from autism subjects exhibit signs of active, ongoing inflammation, as well as alterations in gene pathways associated with immune signaling and immune function. Moreover, many genetic studies have indicated a link between autism and genes that are relevant to both the nervous system and the immune system. Alterations in these pathways can affect function in both systems. Together, these reports suggest that autism may in fact be a systemic disorder with connections to abnormal immune responses." 

Careaga M, Van de Water J, Ashwood P. Immune dysfunction in autism: A pathway to treatment. Neurotherapeutics. 2010;7(3):283-292. doi:10.1016/j.nurt.2010.05.003.

"Here, we singled out one disease from a wide spectrum of neurodevelopmental syndromes commonly called ASD. A central characteristic of ASD patients seems to be autoimmune dysfunction, as is suggested by several lines of evidence on the basis of data indicative of abnormal T-lymphocyte activation, the presence of CNS autoantibodies, and signs of innate immune-system activation in the CNS. As overall lymphocyte numbers are normal in these patients, the CD4+ population (shown to specifically support cognitive function21,23,105) is diminished. Given the critical functions played in CNS development, organization, and function by cytokines, chemokines, macrophages, and T cells, immune malfunction might well have a function in ASD etiology and hence serve as a future therapeutic target."

NC Derecki, E Privman, and J Kipnis: Rett syndrome and other autism spectrum disorders—brain diseases of immune malfunction?

Mol Psychiatry. 2010 April ; 15(4): 355–363. 

“The scientific evidence is quite credible for our autoimmune hypothesis, leading to the identification of autoimmune autistic disorder (AAD) as a major subset of autism. AAD can be identified by immune tests to determine immune problems before administering immunotherapy.”

Singh, VK; Phenotypic expression of autoimmune autistic disorder (AAD): a major subset of autism; Ann Clin Psychiatry. 2009 Jul-Sep;21(3):148-61.

"This present study shows distinct and significant physiological differences in NK cell responses in children with ASD. We clearly demonstrate that there are profound abnormalities in NK cell function in young children recently diagnosed with ASD. An altered NK cell population may have several consequences which could impact upon immune function in ASD and could explain some of the immune findings previously observed in ASD. In addition, fetal/neonatal NK cells may have important roles in neuroimmune interactions during early brain development. Significant differences in NK cells may thus represent a susceptibility factor for ASD."

Enstrom, A M et al. “Altered Gene Expression and Function of Peripheral Blood Natural Killer Cells in Children with Autism.” Brain, behavior, and immunity 23.1 (2009): 124–133. PMC.

"Children with AU have significantly reduced levels of plasma IgG and IgM compared to both DD and TD controls, suggesting an underlying defect in immune function. This reduction in specific Ig levels correlates with behavioral severity, where those patients with the highest scores in the behavioral battery have the most reduced levels of IgG and IgM."

Heuer, Luke et al. “Reduced Levels of Immunoglobulin in Children With Autism Correlates With Behavioral Symptoms.” Autism research : official journal of the International Society for Autism Research 1.5 (2008): 275–283. PMC.

"Interleukin-23 (IL-23) is a survival factor for a newly described population of T lymphocytes, namely Th-17 cells, that secrete IL-17, tumor necrosis factor- alpha (TNFα) and IL-6. It has been shown that Th-17 cells are a pathogenic T cell subset involved in autoimmune and chronic inflammatory diseases...This is the first study to report altered IL-23 production in autism. The decreased plasma IL-23 production observed in children with autism warrants further research as to its affect on the generation and survival of Th-17 cells, a subset important in neuroinflammatory conditions that may include autism."

Enstrom, Amanda et al. “Detection of IL-17 and IL-23 in Plasma Samples of Children with Autism.” American journal of biochemistry & biotechnology 4.2 (2008): 114–120. PMC.

"Several abnormalities were found in the ASD test group: lower production of IL-6 with the TLR2/6 agonist, lower production of IL-1β with the TLR7/8 agonist, and higher production of IL-23 with the TLR4 agonists than case controls in the absence of LPS pre-treatment. These cytokines which were found to be altered in production in the ASD test group are the key regulators in the neuro-immune network [28, 35, 36]. Thus our findings indicate that children in the ASD test group may be less capable of controlling microbial infection in the initial stages, leading to ineffective signalling to the brain. It is also intriguing to find increased production of IL-23 with the TLR4 agonist in the ASD test, since IL-23 is associated with development and maintenance of Th17 cells, a recently defined T-helper cell subset [37, 38]. It is of note that Th17 cells are implicated in various autoimmune and chronic inflammatory diseases including multiple sclerosis and inflammatory bowel diseases [37, 38, 39]. Thus the ASD test group children may be more prone to Th17-mediated inflammatory responses."

Harumi Jyonouchi, Lee Geng, Agnes Cushing-Ruby and Huma Quraishi: Impact of innate immunity in a subset of children with autism spectrum disorders: a case control study; Journal of Neuroinflammation20085:52

"Because ASD patients have a high prevalence of one or more Mycoplasma spp. and sometimes show evidence of infections with Chlamydia pneumoniae, we examined ASD patients for other infections. Also, the presence of one or more systemic infections may predispose ASD patients to other infections, so we examined the prevalence of C. pneumoniae (4/48 or 8.3% positive, odds ratio = 5.6, P < 0.01) and human herpes virus-6 (HHV-6, 14/48 or 29.2%, odds ratio = 4.5, P < 0.01) coinfections in ASD patients. We found that Mycoplasma-positive and -negative ASD patients had similar percentages of C. pneumoniae and HHV-6 infections, suggesting that such infections occur independently in ASD patients. Control subjects also had low rates of C. pneumoniae (1/48 or 2.1%) and HHV-6 (4/48 or 8.3%) infections, and there were no coinfections in control subjects. The results indicate that a large subset of ASD patients shows evidence of bacterial and/or viral infections (odds ratio = 16.5, P < 0.001). The significance of these infections in ASD is discussed in terms of appropriate treatment."

Nicolson, G. L., Gan, R., Nicolson, N. L. and Haier, J. (2007), Evidence for Mycoplasma ssp., Chlamydia pneunomiae, and human herpes virus-6 coinfections in the blood of patients with autistic spectrum disorders. J. Neurosci. Res., 85: 1143–1148. doi:10.1002/jnr.21203

"Autism is a neurodevelopmental disorder characterized by impaired communication and social interaction and may be accompanied by mental retardation and epilepsy. Its cause remains unknown, despite evidence that genetic, environmental, and immunological factors may play a role in its pathogenesis. To investigate whether immune-mediated mechanisms are involved in the pathogenesis of autism, we used immunocytochemistry, cytokine protein arrays, and enzyme-linked immunosorbent assays to study brain tissues and cerebrospinal fluid (CSF) from autistic patients and determined the magnitude of neuroglial and inflammatory reactions and their cytokine expression profiles. Brain tissues from cerebellum, midfrontal, and cingulate gyrus obtained at autopsy from 11 patients with autism were used for morphological studies. Fresh-frozen tissues available from seven patients and CSF from six living autistic patients were used for cytokine protein profiling. We demonstrate an active neuroinflammatory process in the cerebral cortex, white matter, and notably in cerebellum of autistic patients. Immunocytochemical studies showed marked activation of microglia and astroglia, and cytokine profiling indicated that macrophage chemoattractant protein (MCP)-1 and tumor growth factor-beta1, derived from neuroglia, were the most prevalent cytokines in brain tissues. CSF showed a unique proinflammatory profile of cytokines, including a marked increase in MCP-1. Our findings indicate that innate neuroimmune reactions play a pathogenic role in an undefined proportion of autistic patients, suggesting that future therapies might involve modifying neuroglial responses in the brain."

Vargas, D. L., Nascimbene, C., Krishnan, C., Zimmerman, A. W. and Pardo, C. A. (2005), Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol., 57: 67–81. doi:10.1002/ana.20315

"Overactivation within microglia and astrocytes was proved in post-mortem brain bioptates and biomarker studies14,15. Increased autoimmunity mainly due to maternal anti-fetal brain antibodies crossing the placenta during pregnancy was found16. Inflammatory cytokines concentration was found to be altered in serum, placenta and cerebral spinal fluid in children with autism and their relatives 4,15,17. Moreover, skewed production of immunoglobulins or B- and T-cell dysfunction confirmed that humoral and cellular response is altered in individuals with ASD18. Additionally, the presence of gastritis, lymphoid nodular hyperplasia, colonic lymphoid nodular hyperplasia, eosinophilic infiltration and others 12 confirmed that these inflammatory alterations affect the digestive system as well...The immune response in individuals with ASD is altered. These malfunctions may be responsible for ASD development."

P. Szachta, et al. "Immune related factors in pathogenesis of autism spectrum disorders"

Eur Rev Med Pharmacol Sci 2016; 20 (14): 3060-3072

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