Abnormally low autoantibody activity is significantly associated with autism severity

Autism spectrum disorder (ASD) is a neurodevelopmental condition that causes repetitive behaviors and impairments in social communication in children. Scientists are actively studying various aspects of immune imbalances related to autism spectrum disorder to better understand their role in the neurodevelopment of children with autism.

newly Biomedicine The study hypothesized that there is a dysfunction in the self-recognizing properties of the immune system in autism.

Stady: Natural IgG Anti-F (ab’)2 The activity of autoantibodies in children with autism. Image credit: Dubova/Shutterstock


ASD is associated with several immune defects, such as decreased complement proteins, increased number and altered functions of natural killer (NK) cells and T cells, gastrointestinal (GI) inflammation, and uncharacteristic proliferative responses to mitogens. In addition, children with autism often show abnormal levels of B cells and monocytes.

Several studies have indicated that ASD enhances cytokine levels in cerebrospinal fluid (CSF) or serum autoantibody concentrations in the caudate nucleus, myelin basic protein, cerebellar or neuronal membrane proteins, nerve growth factor, neuronal filament protein, and α2-adrenergic receptors. In addition, serum autoantibodies, such as cerebral folate receptor antibodies or anti-nucleosome specific antibodies, have also been found in other brain components of children with autism.

Elevated levels of anti-ganglioside M1 autoantibodies were also observed in the blood serum of children with autism. However, this finding contradicted another study that failed to find any association between autism and anti-ganglioside M1 autoantibodies.

Scientists have recently reported autoimmune processes associated with the central nervous system that cause mental disorders. For example, there have been several reports of children diagnosed with neurogenic autoimmune disorders (PANDAS) associated with streptococcal infection. Similar cases are found in children with autism as well.

The critical role of the immune system is to distinguish between ‘self’ and ‘foreign’. Natural antibodies (NAAbs), which are antibodies present in the serum of healthy, unvaccinated individuals, play an active role in protecting the host from harmful pathogens by modulating the immune response, efficient recognition of environmental antigens, and maintaining tissue homeostasis.

Previous research has shown that most NAAbs are multi-reactive. For example, some NAAbs are able to recognize different autophagic molecules and participate in pathophysiological situations that can determine the beneficial or pathological role of an agent. It should be noted that in several neurodegenerative diseases and mental disorders, changes in NAAbs have been observed.

about studying

Natural antagonist of F (AB’)2 Autoantibodies help recognize the immune self. The current study investigated the role of NAAbs, including the natural antagonist of F (ab’)2 Antibodies in altering mechanisms of self-recognition in autism.

A total of 60 children with autism, consisting of 38 males and 22 females, and 112 developing (TD) controls, 72 males and 40 females, were considered in this study. Both groups share age, gender, and pubertal status.

All participants were Caucasian and had no history of neuroendocrine disease or encephalopathy. Cognitive functioning of ASD children was assessed using the age-appropriate Wechsler intelligence scale and Kaufman K-ABC. Blood samples were collected from the participants to measure the levels of NAAbs.


Serum levels of IgG anti-F (ab’)2 Autoantibodies were significantly lower in the autistic children than in the TD group and were negatively associated with autism severity. In addition, IQ scores were significantly and negatively associated with IgG anti-F (ab’)2 levels in the autism group. Thus, autoantibody levels were more specific for autism than for intellectual disability.

The findings documented in this study are consistent with previous research that revealed lower levels of IgG in children with autism than in the TD group. The current study also indicated the association between low IgG levels and severe autistic behaviors. Previous studies have also demonstrated an association between impaired immunity and the severity of autism.

Considering the function of natural IgG antibody (ab’)2 Autoantibodies are associated with self-recognition, and the results of the current study similarly suggest that impaired autonomic activity in autism leads to a defect in the immune system’s ability to distinguish between self and non-self. The relationship between major histocompatibility complex (MHC) genes and ASDs also favors the autoimmunity basis for autism.


The main limitation is the small sample size of the autism group compared to the control group. This is because children with mild/moderate autism do not go to daycare on a regular basis.

Moreover, drawing blood samples was much easier in the control group than in the ASD group. Another limitation of this study is the inability to identify the underlying mechanism associated with the observed phenomenon.


The present study was the first to highlight the association between an abnormally low normal F(ab’)2 Antibody activity and severe autism. These findings support an autoimmune process in autism, in which a defect in ADS self-recognition mechanisms can manifest. This discovery opens the possibility of future therapeutic inventions for severe autism.

Journal reference:

  • Tordjman, S., Charrier, A., Kazatchkine, M., et al. (2023) Natural IgG Anti-F (ab’)2 The activity of autoantibodies in children with autism. Biomedicine. 11(3), 715. doi: 10.3390/biomedicines11030715

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