Novel maternal autoantibodies in autism spectrum disorder: Implications for screening and diagnosis

Mazón-Cabrera, Rut; Liesenborgs, Jori; Brône, Bert; Vandormael, Patrick; Somers, Veerle

doi:10.3389/fnins.2023.1067833

Cited by 6 publications

(6 citation statements)

References 79 publications

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“…Other G × E interactions with stress have been observed in a range of neuropsychiatric conditions [ 5 ]. With respect to the ASD-specific maternal autoantibodies associated with an increased risk of ASD [ 42 ], recent evidence has revealed important information regarding their effects on regional brain volume and metabolites [ 50 ], and salient maternal antibodies to the fetal brain have recently been identified in samples from the Simons Simplex Collection [ 51 ], the association between maternal autoantibodies to the fetal brain and prenatal stress exposure is not known. We hypothesized that prenatal stress and maternal antibody response might be related due to the known relationship between stress and immune function [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

The Relationship between Maternal Antibodies to Fetal Brain and Prenatal Stress Exposure in Autism Spectrum Disorder

Costa,

Ferguson,

Hawkins

et al. 2023

Metabolites

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Environmental and genetic factors contribute to the etiology of autism spectrum disorder (ASD), but their interaction is less well understood. Mothers that are genetically more stress-susceptible have been found to be at increased risk of having a child with ASD after exposure to stress during pregnancy. Additionally, the presence of maternal antibodies for the fetal brain is associated with a diagnosis of ASD in children. However, the relationship between prenatal stress exposure and maternal antibodies in the mothers of children diagnosed with ASD has not yet been addressed. This exploratory study examined the association of maternal antibody response with prenatal stress and a diagnosis of ASD in children. Blood samples from 53 mothers with at least one child diagnosed with ASD were examined by ELISA. Maternal antibody presence, perceived stress levels during pregnancy (high or low), and maternal 5-HTTLPR polymorphisms were examined for their interrelationship in ASD. While high incidences of prenatal stress and maternal antibodies were found in the sample, they were not associated with each other (p = 0.709, Cramér’s V = 0.051). Furthermore, the results revealed no significant association between maternal antibody presence and the interaction between 5-HTTLPR genotype and stress (p = 0.729, Cramér’s V = 0.157). Prenatal stress was not found to be associated with the presence of maternal antibodies in the context of ASD, at least in this initial exploratory sample. Despite the known relationship between stress and changes in immune function, these results suggest that prenatal stress and immune dysregulation are independently associated with a diagnosis of ASD in this study population, rather than acting through a convergent mechanism. However, this would need to be confirmed in a larger sample.

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Section: Discussionmentioning

confidence: 99%

The Relationship between Maternal Antibodies to Fetal Brain and Prenatal Stress Exposure in Autism Spectrum Disorder

Costa,

Ferguson,

Hawkins

et al. 2023

Metabolites

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“…Considering the existing reports on ASD, autoantibodies against glyceraldehyde-3phosphate dehydrogenase (GAPDH) have previously been identified (Mazón-Cabrera et al, 2023 ). Unfortunately, this specific autoantigen is not included in the Sengenics autoantigen panel.…”

Section: Discussionmentioning

confidence: 99%

High-throughput autoantibody screening identifies differentially abundant autoantibodies in autism spectrum disorder

Mesleh,

Ehtewish,

Lennard

et al. 2023

Front. Mol. Neurosci.

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IntroductionAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by defects in two core domains, social/communication skills and restricted/repetitive behaviors or interests. There is no approved biomarker for ASD diagnosis, and the current diagnostic method is based on clinical manifestation, which tends to vary vastly between the affected individuals due to the heterogeneous nature of ASD. There is emerging evidence that supports the implication of the immune system in ASD, specifically autoimmunity; however, the role of autoantibodies in ASD children is not yet fully understood.Materials and methodsIn this study, we screened serum samples from 93 cases with ASD and 28 healthy controls utilizing high-throughput KoRectly Expressed (KREX) i-Ome protein-array technology. Our goal was to identify autoantibodies with differential expressions in ASD and to gain insights into the biological significance of these autoantibodies in the context of ASD pathogenesis.ResultOur autoantibody expression analysis identified 29 differential autoantibodies in ASD, 4 of which were upregulated and 25 downregulated. Subsequently, gene ontology (GO) and network analysis showed that the proteins of these autoantibodies are expressed in the brain and involved in axonal guidance, chromatin binding, and multiple metabolic pathways. Correlation analysis revealed that these autoantibodies negatively correlate with the age of ASD subjects.ConclusionThis study explored autoantibody reactivity against self-antigens in ASD individuals' serum using a high-throughput assay. The identified autoantibodies were reactive against proteins involved in axonal guidance, synaptic function, amino acid metabolism, fatty acid metabolism, and chromatin binding.

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“…Although these autoantibodies share many common features and can function synergistically to drive disease onset, they appear to differ mechanistically and have unique clinical features. Regardless, eight maternal autoantibodies related to MAR ASD have thus far been identified: CRMP1 and CRMP2, GDA, LDH-A and LDH-B, NSE, STIP1, and YBX1 [ 72 , 73 ]. Overall, two or more of these autoantibodies are required to break immune tolerance and increase the risk of developing symptoms associated with autism ( Table 3 ).…”

Section: Epigenetics and Autoimmunity In Asdmentioning

confidence: 99%

“…Overall, two or more of these autoantibodies are required to break immune tolerance and increase the risk of developing symptoms associated with autism ( Table 3 ). Most recently, three fetal antigens targeted by autoantibodies have been recognized: RPL23, GAPDH, and CAMSAP3 [ 73 ]. These peptides and proteins are predominantly found on neurons and are therefore likely candidates for the manifestation of full-blown MAR ASD.…”

Section: Epigenetics and Autoimmunity In Asdmentioning

confidence: 99%

“…Also, it is not clear whether the maternal immunological memory relies on epigenetic remodeling or whether the immunological responsiveness of the fetus to autoantibody groups is epigenetically linked. Regardless, the adaptive and innate responsiveness of both the mother’s and child’s immune systems appear to be governed by complex epigenetic mechanisms [ 71 , 72 , 73 , 74 ]. Dysregulation of these epigenetic mechanisms, as well as genomic mutations at imprinted gene clusters, may lead to cognitive disability, deficits in social–emotional responsiveness, repetitive or stereotyped motor behavior, improperly coordinated language communication, and gastrointestinal distress.…”

Section: Epigenetics and Autoimmunity In Asdmentioning

confidence: 99%

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Conceptualizing Epigenetics and the Environmental Landscape of Autism Spectrum Disorders

Torres,

Mourad,

Iqbal

et al. 2023

Genes

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Complex interactions between gene variants and environmental risk factors underlie the pathophysiological pathways in major psychiatric disorders. Autism Spectrum Disorder is a neuropsychiatric condition in which susceptible alleles along with epigenetic states contribute to the mutational landscape of the ailing brain. The present work reviews recent evolutionary, molecular, and epigenetic mechanisms potentially linked to the etiology of autism. First, we present a clinical vignette to describe clusters of maladaptive behaviors frequently diagnosed in autistic patients. Next, we microdissect brain regions pertinent to the nosology of autism, as well as cell networks from the bilateral body plan. Lastly, we catalog a number of pathogenic environments associated with disease risk factors. This set of perspectives provides emerging insights into the dynamic interplay between epigenetic and environmental variation in the development of Autism Spectrum Disorders.

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Novel maternal autoantibodies in autism spectrum disorder: Implications for screening and diagnosis

Cited by 6 publications

References 79 publications

The Relationship between Maternal Antibodies to Fetal Brain and Prenatal Stress Exposure in Autism Spectrum Disorder

The Relationship between Maternal Antibodies to Fetal Brain and Prenatal Stress Exposure in Autism Spectrum Disorder

High-throughput autoantibody screening identifies differentially abundant autoantibodies in autism spectrum disorder

Conceptualizing Epigenetics and the Environmental Landscape of Autism Spectrum Disorders

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