Prenatal toxoplasmosis antibody and childhood autism

Spann, Marisa; Sourander, André; Surcel, Heljä‐Marja; Hinkka‐Yli‐Salomäki, Susanna; Brown, Alan S.

doi:10.1002/aur.1722

Cited by 37 publications

(26 citation statements)

References 30 publications

(47 reference statements)

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“…On the other hand, our results are consistent with results from a few studies investigating the relationship between maternal IgG antibodies directed against other specific antigens, such as those derived from Toxoplasma gondii (T. gondii), and ASD in offspring (24)(25)(26) in which high levels of maternal IgG were associated with decreased offspring risk of ASD.…”

Section: Discussionsupporting

confidence: 90%

Maternal antibodies to gliadin and autism spectrum disorders in offspring - A population-based case-control study in Sweden

Gardner

Samuelsson

Severance

et al. 2020

Preprint

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ObjectiveIndividuals diagnosed with autism spectrum disorders (ASD) are reported to have higher levels of antibodies directed towards gliadin, a component of wheat gluten. However, no study has examined such antibodies in etiologically-relevant periods before diagnosis. The objective of this study is to investigate if maternal levels of immunoglobulin G antibodies directed at gliadin, during pregnancy and at the time of birth, are associated with ASD in offspring. MethodsIn this population-based study set in Sweden with 921 ASD cases and 1090 controls, we analyzed levels of anti-gliadin antibodies (AGA) in archived neonatal dried blood spots (NDBS, as maternal IgG is transferred to the fetus) and in paired maternal sera collected earlier in pregnancy for a subset of 547 cases and 428 controls. We examined associations to any ASD diagnosis and considering common comorbidities (i.e. intellectual disability [ID] and attentiondeficit/hyperactivity disorder [ADHD]). We compared 206 ASD cases to their unaffected siblings to examine the potential for confounding by shared familial factors. ResultsHigh levels (³90 th percentile) of maternal AGA were associated with decreased odds of ASD, particularly ASD with comorbid ID, when measured in NDBS (OR 0.51, 95% CI 0.30-0.87) with a similar trend in maternal sera (0.55, 0.24-1.29). High levels of maternal AGA were similarly associated with lower odds of ASD with ID in the sibling comparison. ConclusionsThis first study of exposure to AGA in the pre-and perinatal periods suggests that high levels of maternal AGA are associated with lower odds of ASD with ID. SF2. Maternal IgG AGA levels during pregnancy and offspring odds of ASDThe figure displays crude and adjusted OR's and 95 % CI for high levels of maternal AGA (i.e. levels in the 80-90 and > 90 th percentile categories, based on the distribution among controls) when measured in NDBS and in MS, for ASD in offspring as well as for ASD subtyped by comorbidities. The adjusted models for AGA in NDBS were adjusted for sex, maternal age, maternal BMI, maternal psychiatric history, maternal immigrant status, income, birth order, gestational age at birth and mode of delivery. The adjusted models for AGA in MS were adjusted for sex, maternal age, maternal BMI, maternal psychiatric history, maternal immigrant status, income, maternal total IgG and birth order.Abbreviations; ADHD = Attention-deficit hyperactive disorder, AGA = Antigliadin antibodies, ASD = Autism spectrum disorders, CI = Confidence interval, ID =Intellectual disability, MS = Maternal, NDBS = Neonatal dried blood spots, OR = Odds ratio

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Section: Discussionsupporting

confidence: 90%

Maternal antibodies to gliadin and autism spectrum disorders in offspring - A population-based case-control study in Sweden

Gardner

Samuelsson

Severance

et al. 2020

Preprint

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“…The increased risk of ASD in children has also been associated with bacterial infections: Premature children with proven bacteremia in the first weeks of life have worse neurocognitive test scores [96] and present neurological dysfunction at school ages [97]. Also, parasitic infections such as Toxoplasma gondii have been associated with an increased risk in the development of ASD [98]. Together, these data strengthen the critical role of immune dysregulation during the critical period of development, predisposing to the onset of neurodevelopmental diseases.…”

Section: Neuroinflammation and Microglial Function In Infectious Condmentioning

confidence: 84%

Environmental Signals on Microglial Function during Brain Development, Neuroplasticity, and Disease

Chagas

Sandre

Ribeiro

et al. 2020

IJMS

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Recent discoveries on the neurobiology of the immunocompetent cells of the central nervous system (CNS), microglia, have been recognized as a growing field of investigation on the interactions between the brain and the immune system. Several environmental contexts such as stress, lesions, infectious diseases, and nutritional and hormonal disorders can interfere with CNS homeostasis, directly impacting microglial physiology. Despite many encouraging discoveries in this field, there are still some controversies that raise issues to be discussed, especially regarding the relationship between the microglial phenotype assumed in distinct contexts and respective consequences in different neurobiological processes, such as disorders of brain development and neuroplasticity. Also, there is an increasing interest in discussing microglial-immune system cross-talk in health and in pathological conditions. In this review, we discuss recent literature concerning microglial function during development and homeostasis. In addition, we explore the contribution of microglia to synaptic disorders mediated by different neuroinflammatory outcomes during pre-and postnatal development, with long-term consequences impacting on the risk and vulnerability to the emergence of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders.

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“…Severe or multiple bacterial infections in pregnancy, were similarly associated with increased risk of ASD in children (Zerbo et al, 2015). Recent data extended this correlation to parasites, as suggested by a study (Spann et al, 2017) showing that low circulating maternal immunoglobulin levels (Ig) against Toxoplasma gondii is linked to increased odds of ASD in offspring, whereas high levels of Ig predict the opposite.…”

Section: Cytokine Dysregulation In Fetal Lifementioning

confidence: 86%

Nerve cells developmental processes and the dynamic role of cytokine signaling

Guidolin

Fede

Tortorella

2018

Intl J of Devlp Neuroscience

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The stunning diversity of neurons and glial cells makes possible the higher functions of the central nervous system (CNS), allowing the organism to sense, interpret and respond appropriately to the external environment. This cellular diversity derives from a single primary progenitor cell type initiating lineage leading to the formation of both differentiated neurons and glial cells. The processes governing the differentiation of the progenitor pool of cells into mature nerve cells will be here briefly reviewed. They involve morphological transformations, specialized modes of cell division, migration, and controlled cell death, and are regulated through cell‐cell interactions and cues provided by the extracellular matrix, as well as by humoral factors from the cerebrospinal fluid and the blood system. In this respect, a quite large body of studies have been focused on cytokines, proteins representing the main signaling network that coordinates immune defense and the maintenance of homeostasis. At the same time, they are deeply involved in CNS development as regulatory factors. This dual role in the nervous system appears of particular relevance for CNS pathology, since cytokine dysregulation (occurring as a consequence of maternal infection, exposure to environmental factors or prenatal hypoxia) can profoundly impact on neurodevelopment and likely influence the response of the adult tissue during neuroinflammatory events.

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Prenatal toxoplasmosis antibody and childhood autism

Cited by 37 publications

References 30 publications

Maternal antibodies to gliadin and autism spectrum disorders in offspring - A population-based case-control study in Sweden

Maternal antibodies to gliadin and autism spectrum disorders in offspring - A population-based case-control study in Sweden

Environmental Signals on Microglial Function during Brain Development, Neuroplasticity, and Disease

Nerve cells developmental processes and the dynamic role of cytokine signaling

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