Autistic people are diagnosed with autoimmune conditions more often than the general population, and children born to mothers with autoimmune diseases face a modestly higher chance of developing autism. A population-based birth cohort study found that individuals meeting research criteria for autism were about 1.7 times more likely to have an autoimmune disease than those without autism.1PubMed Central. Risk of Autoimmune Disease in Research-Identified Cases of Autism Spectrum Disorder: A Longitudinal, Population-Based Birth Cohort Study The relationship goes deeper than a statistical overlap, though, touching on everything from what happens in utero to how the immune system behaves in autistic children and adults.
How Often Do Autoimmune Conditions Show Up Alongside Autism?
Several large studies have tried to quantify the overlap. One analysis of health records found that autoimmune diseases were diagnosed more frequently in children with autism than in matched controls, with psoriasis appearing at roughly twice the rate. Allergies were also elevated in the autism group, though asthma was actually less common.2PubMed Central. Immune mediated conditions in autism spectrum disorders A Taiwanese population-based study found a fourfold increase in the odds of type 1 diabetes among people with autism and a trend toward higher rates of Crohn’s disease.3Research in Autism Spectrum Disorders. Comorbidity of allergic and autoimmune diseases in patients with autism spectrum disorder: A nationwide population-based study These numbers vary from study to study and country to country, but the direction is consistent: autoimmune conditions are overrepresented in autistic populations.
The longitudinal birth cohort study mentioned earlier also found that the link appeared stronger in males, who had about twice the risk of developing an autoimmune disease compared to non-autistic males, while the association in females did not reach statistical significance on its own.1PubMed Central. Risk of Autoimmune Disease in Research-Identified Cases of Autism Spectrum Disorder: A Longitudinal, Population-Based Birth Cohort Study That sex difference will come up again later in this article, because it threads through multiple aspects of the autism-immunity story.
When a Mother Has an Autoimmune Disease
The connection is not limited to the autistic person’s own health. Family history matters, and maternal autoimmune disease in particular has attracted the most research attention. A nationwide cohort study found that, after adjusting for confounders, mothers with any autoimmune disease had roughly a 25% higher likelihood of having a child later diagnosed with autism. The risk was specifically elevated for mothers with rheumatoid arthritis and Sjögren’s syndrome.4PubMed Central. Maternal autoimmune disease and risk of offspring autism spectrum disorder – a nationwide population-based cohort study
Another study examined both parents and found that a maternal autoimmune diagnosis carried about a 60% increase in the odds of an autism diagnosis in the child, while paternal autoimmune disease showed roughly a 40% increase. Type 1 diabetes, myasthenia gravis, and rheumatic fever were among the specific maternal conditions associated with elevated risk, though most were rare enough that the estimates were imprecise.5PubMed Central. Parental Autoimmune Diseases Associated With Autism Spectrum Disorders in Offspring A separate study found similar patterns, with maternal rheumatoid arthritis and celiac disease linked to increased autism risk, and a family history of type 1 diabetes linked to the narrower diagnosis of infantile autism.6Pediatrics. Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders
An important caveat: these are population-level statistics. The absolute risk of autism remains low even when a mother has an autoimmune condition. A 25% relative increase applied to a low base rate still yields a small absolute number. Most mothers with autoimmune diseases have neurotypical children.
What Happens During Pregnancy
The leading hypothesis for why maternal autoimmune disease might influence autism risk centers on the immune environment of the womb, not the disease itself being passed to the child. When a pregnant person’s immune system becomes activated, whether by an infection, a flare of autoimmune disease, or some other trigger, the resulting flood of immune signaling molecules can affect fetal brain development. This concept, called maternal immune activation, has been studied extensively in animal models. Experiments in mice, rats, and primates have shown that triggering a strong immune response during pregnancy leads to measurable changes in brain development and social behavior in offspring.7PubMed Central. Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates
At the molecular level, maternal immune activation in rodents disrupts the expression of genes that are also known to be affected in autism, particularly genes involved in how brain cells communicate at synapses. These gene expression changes are not fleeting; some persist and mirror patterns seen in autistic brain tissue later in life.8PubMed Central. Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder In humans, research has linked maternal immune activation during pregnancy to greater difficulties with social and adaptive behaviors in children who go on to be diagnosed with autism.9Scientific Reports. Maternal immune activation during pregnancy is associated with more difficulties in socio-adaptive behaviors in autism spectrum disorder
A separate line of research has identified another prenatal pathway: some mothers produce antibodies that react against proteins in the fetal brain. These maternal autoantibodies can cross the placenta, and when they target developing brain tissue, they may interfere with normal neurodevelopment. The specific targets of these antibodies have been identified, and while the exact process by which they are generated remains unclear, their presence has been linked to autism outcomes in the child.10PubMed Central. Maternal Anti-Fetal Brain IgG Autoantibodies and Autism Spectrum Disorder: Current Knowledge and its Implications for Potential Therapeutics
Immune Differences in Autistic People Themselves
The connection is not just about what happens before birth. Autistic individuals show a range of immune differences compared to neurotypical controls. A comprehensive meta-analysis covering 54 immune signaling molecules found that autistic people had elevated levels of several pro-inflammatory markers, pointing to a pattern of heightened inflammatory activity at the group level.11Molecular Psychiatry. Atypical cytokine profiles in people on the autism spectrum: a comprehensive systematic review and meta-analysis including 54 cytokines These immune signaling imbalances have been documented repeatedly, though researchers still debate whether they play a role in causing autism-related traits or simply reflect an underlying genetic or environmental factor affecting both the immune system and the brain.12PubMed Central. Cytokine dysregulation in autism spectrum disorders (ASD): possible role of the environment
The cellular side of immunity also looks different. T cells, which are key players in the body’s defense against pathogens, show altered behavior in autistic children. Studies have found that when T cells from autistic children are stimulated, they do not respond the way they do in typically developing children, showing reduced activation on certain surface markers.13PubMed Central. Altered T cell responses in children with autism An integrative review noted that this dysregulated T cell activity, characterized by increased inflammatory signaling and disrupted regulatory mechanisms, has been observed consistently across multiple laboratories and geographic regions.14PubMed. Toward a better understanding of T cell dysregulation in autism: An integrative review
One especially relevant finding is a shift in the balance between regulatory T cells, which dampen immune responses and prevent autoimmunity, and Th17 cells, which drive inflammation. A meta-analysis found that autistic individuals had significantly fewer regulatory T cells and significantly more Th17 cells compared to controls.15PubMed Central. Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysis This particular imbalance is well known in autoimmune disease research. When regulatory T cells cannot properly restrain immune activity, the body becomes more prone to attacking its own tissues. Whether this same mechanism contributes directly to autism-related brain changes or simply reflects shared biology between autism and autoimmunity is still being worked out.
Autoantibodies Targeting the Brain
Beyond the general immune imbalances, some autistic children produce antibodies that specifically react against their own brain proteins. Researchers have found that antibodies targeting cerebellar proteins were significantly more common in children with autism than in controls.16PubMed Central. Autoantibodies to cerebellum in children with autism associate with behavior Broader screenings have shown widespread autoreactivity to brain tissue in autistic patients and their families, leading some researchers to suggest that these antibodies may reflect the immune system responding to a brain injury that occurred during early development rather than causing the injury in the first place.17PubMed. Autoantibody repertoires to brain tissue in autism nuclear families
This distinction matters practically. If autoantibodies against brain tissue are a consequence of earlier neurodevelopmental disruption rather than a cause, treating the autoantibodies might not change the underlying condition. The question of cause versus consequence remains one of the hardest puzzles in this field.
Neuroinflammation in the Brain
Postmortem and brain imaging studies have provided direct evidence that something inflammatory is happening in the brains of autistic individuals. Microglia, the brain’s resident immune cells, appear to be chronically activated in autism, and this has been documented across multiple brain regions.18PubMed Central. Evidence of microglial activation in autism and its possible role in brain underconnectivity A brain imaging study using a tracer that binds to activated microglia found increased signals in the cerebellum, brainstem, and several cortical areas in young adults with autism compared to controls, with no brain regions showing the reverse pattern.19JAMA Psychiatry. Microglial Activation in Young Adults With Autism Spectrum Disorder
Microglia do more than just fight infection. During brain development, they help prune unnecessary neural connections and shape how brain circuits form. If they are persistently activated, they may over-prune or under-prune, potentially contributing to the connectivity differences seen in autism. This is a plausible mechanism, but it is worth noting that the imaging studies involved small samples and the tracer used is not perfectly specific to microglia. The finding is suggestive, not definitive.
Folate Receptor Autoantibodies
One of the more clinically actionable findings in this space involves autoantibodies that block folate receptors in the brain. Folate is essential for neurodevelopment, and the brain has a dedicated transport system to pull it across the blood-brain barrier. In some children, the body produces antibodies that block this transport system. A study measuring these antibodies in 93 children with autism found them in about three-quarters of participants, and in a subset of those children, antibody levels correlated with reduced folate concentrations in cerebrospinal fluid.20PubMed Central. Cerebral folate receptor autoantibodies in autism spectrum disorder
This matters because there is a potential workaround. A form of folate called leucovorin can bypass the blocked receptor and get into the brain through alternative routes. In children who test positive for these autoantibodies, leucovorin supplementation has shown some promise for improving symptoms, though larger trials are still needed. During pregnancy, folate receptor autoantibodies can also interfere with folate delivery to the developing fetus, which may connect maternal autoimmunity to prenatal risk.21PubMed Central. Folate Receptor Alpha Autoantibodies in Autism Spectrum Disorders: Diagnosis, Treatment and Prevention
The Gut as a Meeting Point
Gastrointestinal problems are strikingly common in autistic individuals, and the gut is one of the body’s largest immune organs. This makes it a natural meeting point for the autism-autoimmunity story. Conditions including inflammatory bowel disease, celiac disease, food allergies, and altered gut permeability have all been reported at higher-than-expected rates in autism.22Revista Brasileira de Psiquiatria. Opioid peptides and gastrointestinal symptoms in autism spectrum disorders The mechanisms that may link autism and gut problems include intestinal inflammation, disrupted gut microbiome composition, changes in gut permeability, and immune-mediated food sensitivities.23PubMed Central. Gastrointestinal symptoms and autism spectrum disorder: links and risks – a possible new overlap syndrome
Gut problems in autistic children are easy to underdiagnose because communication difficulties can make it harder for children to report pain or discomfort. Some behavioral changes attributed to autism, like irritability or self-injurious behavior, may in fact be driven by unrecognized gastrointestinal distress. Clinicians who work with autistic patients are increasingly aware of this overlap, but it still goes undetected more often than it should.
Shared Genetics Between Autism and Autoimmunity
The overlap between autism and autoimmune conditions is not purely environmental. Genetic analyses have found that some of the same gene variants that increase risk for autoimmune diseases also show up in autism risk profiles. At the genome-wide level, autism has been found to be positively correlated with allergic diseases and correlated with rheumatoid arthritis, lupus, and lymphocyte counts. In the general population, genetic scores that predict higher risk for lupus, rheumatoid arthritis, and allergies were also associated with more autistic traits, particularly in the domains of rigidity and childhood behavior patterns.24PubMed Central. Genetic relationship between the immune system and autism
This genetic overlap suggests that the connection between autism and autoimmunity is not simply one condition causing the other. Instead, some of the same biological pathways that influence immune regulation also influence brain development. A person who inherits variants that skew immune function in a certain direction may be simultaneously nudged toward both autoimmune susceptibility and neurodevelopmental differences.
Why the Male Skew Matters
Autism is diagnosed roughly four times more often in males than in females, and autoimmune diseases have their own well-documented sex differences (though in the opposite direction for most conditions, with females more commonly affected). One hypothesis proposes that the normal process of brain masculinization during fetal development places males closer to a vulnerability threshold. If inflammation or immune disruption occurs during critical windows of brain development, males may be more easily pushed past that threshold than females.25PubMed Central. Convergence of Sex Differences and the Neuroimmune System in Autism Spectrum Disorder
This framing helps explain a paradox: why would maternal autoimmune disease, which is more common in women, increase the risk of autism primarily in male offspring? If males are developmentally closer to a tipping point, even a modest immune insult during pregnancy could have a disproportionate effect. This remains a theoretical framework rather than a proven mechanism, but it aligns with the epidemiological data showing that the autoimmune-autism link may be stronger in males.1PubMed Central. Risk of Autoimmune Disease in Research-Identified Cases of Autism Spectrum Disorder: A Longitudinal, Population-Based Birth Cohort Study
Maternal Autoantibody Testing as a Biomarker
One of the most concrete developments to come out of this research is the identification of specific maternal autoantibody patterns that are strongly associated with autism in the child. Researchers have identified combinations of antibodies targeting specific brain proteins that appear almost exclusively in mothers of autistic children. In one study, the pattern involving antibodies against two proteins called CRMP1 and GDA was found to increase the odds of autism more than 30-fold, while the CRMP1 plus CRMP2 combination increased odds about 26-fold.26Molecular Psychiatry. Risk assessment analysis for maternal autoantibody-related autism (MAR-ASD): a subtype of autism
A follow-up study tested whether these patterns held up in a larger, more diverse sample. Roughly 10% of mothers of autistic children showed reactivity to one or more of these established autoantibody patterns, compared to just 1% of the general population controls. The CRMP1 plus CRMP2 pattern in particular increased the odds of an autism diagnosis 16-fold.27PubMed Central. Maternal autoantibody profiles as biomarkers for ASD and ASD with co-occurring intellectual disability These numbers are striking, but a few things keep them from being ready for routine clinical use. The patterns identify only a subset of autism cases, those driven by this particular maternal autoantibody mechanism. And the high odds ratios partly reflect the rarity of the patterns in the control population. Still, this is probably the closest the field has come to a prenatal biological marker for autism risk, and it is being actively developed as a potential screening tool.
Immune-Targeted Treatments
If immune dysfunction plays a role in at least some cases of autism, it is natural to ask whether treatments targeting the immune system could help. Intravenous immunoglobulin, a therapy commonly used in autoimmune conditions, has been tried in small studies of autistic children. A pilot study reported improvements in social interaction, communication, and repetitive behaviors, along with reductions in markers of neuroinflammation.28PubMed. A pilot study of high-dose intravenous immunoglobulin 5% for autism: Impact on autism spectrum and markers of neuroinflammation A separate open-label study in children with signs of autoimmune brain inflammation found that most parents reported improvement, with measurable gains on behavioral and social responsiveness scales.29PubMed Central. Intravenous immunoglobulin for the treatment of autoimmune encephalopathy in children with autism A more recent prospective study in children with documented immune dysregulation also found significant improvements in social cognition and communication after treatment, with only mild side effects.30PubMed Central. Efficacy and Safety of Intravenous Immunoglobulin in Children with Autism Spectrum Disorder with Immune Dysregulation: A Prospective, Open-Label, Single-Arm Study
These results are genuinely interesting, but they come with serious caveats. Every study published so far has been small, unblinded, or both. Without placebo-controlled trials, it is impossible to separate real immune-mediated improvement from placebo effects and observer bias, especially when the outcome measures depend on parent or clinician ratings. IVIG is also expensive, requires repeated infusions, and carries its own risks. No major guideline currently recommends it as a standard treatment for autism. What these studies do support is further investigation, particularly in the subset of autistic individuals who have clear signs of immune dysregulation, rather than in autism broadly.
Conditions That Can Mimic or Complicate the Picture
The autism-autoimmunity overlap also raises practical diagnostic challenges. Some autoimmune and post-infectious conditions can produce behavioral symptoms that resemble autism or overlap with it. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) and PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) involve sudden behavioral changes triggered by infection or immune responses, and children with these conditions can present with obsessive symptoms, behavioral regression, and social withdrawal that might initially suggest autism.31PubMed Central. PANDAS and PANS: Clinical, Neuropsychological, and Biological Characterization of a Monocentric Series of Patients and Proposal for a Diagnostic Protocol The key difference is the sudden onset: autism develops gradually through early childhood, while PANDAS and PANS typically strike abruptly. Recognizing the difference matters because the treatment approaches are entirely different.
Autoimmune encephalitis is another condition worth knowing about. It can cause cognitive and behavioral changes in children and adults, sometimes including social withdrawal and repetitive behaviors. In rare cases, what looks like a worsening of autism symptoms may actually be a treatable autoimmune condition layered on top of it. Clinicians working with autistic patients who experience sudden or dramatic behavioral changes are increasingly inclined to screen for these treatable immune-mediated causes.
Environmental Factors and Epigenetics
Genes set the stage, but environmental exposures influence whether and how immune-related risks manifest. Infections during pregnancy, air pollution, and other environmental toxicants have all been proposed as triggers that could activate the maternal immune system and push a genetically susceptible pregnancy toward altered neurodevelopment. These triggers may compound the risk in cases where autoimmune disease or folate deficiency already exists.32PubMed Central. Neurodevelopmental Impact of Maternal Immune Activation and Autoimmune Disorders, Environmental Toxicants and Folate Metabolism on Autism Spectrum Disorder Epigenetic changes, modifications to how genes are read without changing the DNA itself, are one mechanism by which these environmental exposures could have lasting effects. The field is still early in understanding which specific exposures matter most and at what doses, but the general principle that gene-environment interaction drives risk is well accepted.
For people planning pregnancies who have autoimmune conditions, this does not mean anything catastrophic. The absolute risk increase is modest. What it does mean is that managing autoimmune flares during pregnancy, ensuring adequate folate intake, and working with a healthcare provider familiar with both autoimmune disease and pregnancy are all reasonable, evidence-informed steps. None of this is cause for alarm; it is cause for good prenatal care.