Pathogen-mediated NMDA receptor autoimmunity and cellular barrier dysfunction in schizophrenia

Kannan, Geetha; Gressitt, Kristin L.; Yang, Stephanie; Stallings, Cassie; Katsafanas, Emily; Schweinfurth, Lucy; Savage, Christina; Adamos, Maria; Sweeney, Kevin; Origoni, Andrea; Khushalani, Sunil; Bahn, Sabine; Leweke, F. Markus; Dickerson, Faith; Yolken, Robert H.; Pletnikov, Mikhail V.; Severance, Emily G.

doi:10.1038/tp.2017.162

Cited by 49 publications

(42 citation statements)

References 65 publications

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“…Antibodies were detectable in circulation by 2 weeks postinfection, increased gradually over the next 2 months, and remained high until the end of the experiment. In an earlier study (17), the time course of NMDAR antibody generation in mice with T. gondii type II infection showed a similar pattern.…”

Section: Resultsmentioning

confidence: 52%

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Chronic Toxoplasma gondii Infection Induces Anti-N-Methyl-d-Aspartate Receptor Autoantibodies and Associated Behavioral Changes and Neuropathology

Li¹,

Viscidi²,

Kannan

et al. 2018

Infect Immun

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Anti-NMDA receptor (NMDAR) autoantibodies have been postulated to play a role in the pathogenesis of NMDAR hypofunction, which contributes to the etiology of psychotic symptoms. is a pathogen implicated in psychiatric disorders and associated with elevation of NMDAR autoantibodies. However, it remains unclear whether parasite infection is the cause of NMDAR autoantibodies. By using mouse models, we found that NMDAR autoantibody generation had a strong temporal association with tissue cyst formation, as determined by MAG1 antibody seroreactivity ( = 0.96; < 0.0001), which is a serologic marker for the cyst burden. The presence of MAG1 antibody response, but not IgG response, was required for NMDAR autoantibody production. The pathogenic relevance of NMDAR autoantibodies to behavioral abnormalities (blunted response to amphetamine-triggered activity and decreased locomotor activity and exploration) and reduced expression of synaptic proteins (the GLUN2B subtype of NMDAR and PSD-95) has been demonstrated in infected mice. Our study suggests that NMDAR autoantibodies are specifically induced by persistent infection and are most likely triggered by tissue cysts. NMDAR autoantibody seroreactivity may be a novel pathological hallmark of chronic toxoplasmosis, which raises questions about NMDAR hypofunction and neurodegeneration in the infected brain.

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Section: Resultsmentioning

confidence: 52%

“…Emerging clinical observations suggest that infectious agents, such as herpesvirus, may trigger NMDAR autoantibodies (16). Interestingly, recent studies have reported that NMDAR autoantibodies are present in chronic murine toxoplasmosis (6,17). This raises the question of whether T. gondii is the origin of the autoantibodies.…”

mentioning

confidence: 99%

Chronic Toxoplasma gondii Infection Induces Anti-N-Methyl-d-Aspartate Receptor Autoantibodies and Associated Behavioral Changes and Neuropathology

Li¹,

Viscidi²,

Kannan

et al. 2018

Infect Immun

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“…Exposure to Toxoplasma has been associated with increased blood-brain barrier permeability in SZ subjects (Kannan et al, 2017) and with substantial and widespread immune activation including increased C reactive protein (Tomasik et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Latent toxoplasma infection in real-world schizophrenia: Results from the national FACE-SZ cohort

Boyer

Godin

Chéreau

et al. 2018

Schizophrenia Research

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The present findings suggest that Toxoplasma is almost 3 times more frequent in SZ population compared to general population in France. The potential cerebral underpinnings of the association of latent Toxoplasma infection and the above-mentioned outcomes have been discussed. Future studies should confirm that TATA may be effective to reduce Toxoplasma-associated depressive symptoms and low-grade peripheral inflammation.

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“…Vaccine-induced GRA mediated GR dysfunction can explain a wide variety of disorders including autism (42), attention deficit hyperactivity (43,44), epilepsy (45,46), schizophrenia (47,48), autoimmune encephalitis (17,(49)(50)(51)(52), and psychosis (17,47,48,52,53).…”

Section: Neuropsychiatric Disordersmentioning

confidence: 99%

Role of NMDA receptor autoimmunity induced by food protein containing vaccines, in the etiology of autism, type 1 diabetes, neuropsychiatric and neurodegenerative disorders

2019

IJPR

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Vaccines contain numerous animal and plant proteins (soy, peanut, sesame, maize, wheat, etc.). Vaccine excipients are derived from plant or animal sources. The mechanism of animal protein induced autoimmunity was previously described. Following a report associating maternal gluten intake to type 1 diabetes in the offspring, plant proteins were investigated. The Pandemrix vaccine induced narcolepsy due to molecular mimicry between a H1N1 nucleoprotein peptide in the vaccine and the human hypocretin receptor 2. The BLASTP match score for this peptide was used as a baseline. BLASTP showed strong sequence alignment between gliadin, a wheat protein, and the human ionotropic N-methyl-D-aspartate receptor (NMDAR). Analyzing further, strong sequence alignment was found between soy, peanut, sesame, maize, wheat and human glutamate receptors (GR), both ionotropic and metabotropic. There are reports of boosted wheat allergy and de novo synthesis of NMDAR antibodies following immunization. Once immunized with plant derived antigens, antibody levels will be increased by dietary exposure to these antigens. GR are expressed in the brain, heart, pancreas and the T cells of the immune system. Vaccine induced GR antibodies (GRA) disrupt or destroy GR thus precipitating numerous disorders. This explains the epidemic of food intolerances and food associated immune mediated disorders. Intestinal barrier disruption has been proposed as a cause for food associated autoimmune disorders. However, intestinal barrier disruption may itself be the result of GRA. GRA also disrupt the bloodbrain barrier. This allows other anti-brain antibodies access to their targets. Vaccine-induced GRA can therefore explain a wide variety of disorders including autism, type 1 diabetes, attention deficit hyperactivity, epilepsy, schizophrenia, autoimmune encephalitis, Huntington's, Parkinson's, dementia, cancer and allergies. The ultimate solution is to immediately remove all non-target proteins from all vaccines.

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Pathogen-mediated NMDA receptor autoimmunity and cellular barrier dysfunction in schizophrenia

Cited by 49 publications

References 65 publications

Chronic Toxoplasma gondii Infection Induces Anti-N-Methyl-d-Aspartate Receptor Autoantibodies and Associated Behavioral Changes and Neuropathology

Chronic Toxoplasma gondii Infection Induces Anti-N-Methyl-d-Aspartate Receptor Autoantibodies and Associated Behavioral Changes and Neuropathology

Latent toxoplasma infection in real-world schizophrenia: Results from the national FACE-SZ cohort

Role of NMDA receptor autoimmunity induced by food protein containing vaccines, in the etiology of autism, type 1 diabetes, neuropsychiatric and neurodegenerative disorders

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