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Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections

Movement, behavioral, and neuropsychiatric disorders in children have been linked to infections and a group of anti-neuronal autoantibodies, implying dopamine receptor-mediated encephalitis within the basal ganglia. The purpose of this study was to determine if anti-neuronal biomarkers, when used as...

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Autores principales: Chain, Jennifer L., Alvarez, Kathy, Mascaro-Blanco, Adita, Reim, Sean, Bentley, Rebecca, Hommer, Rebecca, Grant, Paul, Leckman, James F., Kawikova, Ivana, Williams, Kyle, Stoner, Julie A., Swedo, Susan E., Cunningham, Madeleine W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328706/
https://www.ncbi.nlm.nih.gov/pubmed/32670106
http://dx.doi.org/10.3389/fpsyt.2020.00564
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author Chain, Jennifer L.
Alvarez, Kathy
Mascaro-Blanco, Adita
Reim, Sean
Bentley, Rebecca
Hommer, Rebecca
Grant, Paul
Leckman, James F.
Kawikova, Ivana
Williams, Kyle
Stoner, Julie A.
Swedo, Susan E.
Cunningham, Madeleine W.
author_facet Chain, Jennifer L.
Alvarez, Kathy
Mascaro-Blanco, Adita
Reim, Sean
Bentley, Rebecca
Hommer, Rebecca
Grant, Paul
Leckman, James F.
Kawikova, Ivana
Williams, Kyle
Stoner, Julie A.
Swedo, Susan E.
Cunningham, Madeleine W.
author_sort Chain, Jennifer L.
collection PubMed
description Movement, behavioral, and neuropsychiatric disorders in children have been linked to infections and a group of anti-neuronal autoantibodies, implying dopamine receptor-mediated encephalitis within the basal ganglia. The purpose of this study was to determine if anti-neuronal biomarkers, when used as a group, confirmed the acute disease in Sydenham chorea (SC) and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). IgG autoantibodies against four neuronal autoantigens (tubulin, lysoganglioside G(M1), and dopamine receptors D1 and D2) were detected in SC sera (N=8), sera and/or cerebrospinal fluid (CSF) from two groups of PANDAS cases (N=25 first group and N=35 second group), sera from Tourette's syndrome (N=18), obsessive-compulsive disorder (N=25), attention deficit hyperactivity disorder (N=18), and healthy controls (N=28) by direct enzyme-linked immunosorbent assay (ELISA). IgG specific for neuronal autoantigens was significantly elevated during the acute symptomatic phase, and the activity of calcium/calmodulin-dependent protein kinase II (CaMKII) pathway was significantly elevated in human neuronal cells. Five assays confirmed the disease in SC and in two groups of children with PANDAS. In 35 acute onset PANDAS patients, 32 sera (91.4%) were positive for one or more of the anti-neuronal autoantibodies compared with 9 of 28 healthy controls (32.1%, p<0.0001). Importantly, CSF of 32 (91.4%) PANDAS patients had one or more detectable anti-neuronal autoantibody titers and CaMKII activation. Among healthy control subjects with elevated serum autoantibody titers for individual antigens, none (0%) were positively associated with elevated positive CaMKII activation, which was a striking contrast to the sera of PANDAS subjects, who had 76–89% positive association with elevated individual autoantibody titers and positive CaMKII activity. At 6 months follow-up, symptoms improved for more than 80% of PANDAS subjects, and serum autoantibody titers also significantly decreased. Results reported herein and previously published studies in our laboratory suggest the antibody biomarkers may be a useful adjunct to clinical diagnosis of SC, PANDAS, and related disorders and are the first known group of autoantibodies detecting dopamine receptor-mediated encephalitis in children.
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spelling pubmed-73287062020-07-14 Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections Chain, Jennifer L. Alvarez, Kathy Mascaro-Blanco, Adita Reim, Sean Bentley, Rebecca Hommer, Rebecca Grant, Paul Leckman, James F. Kawikova, Ivana Williams, Kyle Stoner, Julie A. Swedo, Susan E. Cunningham, Madeleine W. Front Psychiatry Psychiatry Movement, behavioral, and neuropsychiatric disorders in children have been linked to infections and a group of anti-neuronal autoantibodies, implying dopamine receptor-mediated encephalitis within the basal ganglia. The purpose of this study was to determine if anti-neuronal biomarkers, when used as a group, confirmed the acute disease in Sydenham chorea (SC) and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). IgG autoantibodies against four neuronal autoantigens (tubulin, lysoganglioside G(M1), and dopamine receptors D1 and D2) were detected in SC sera (N=8), sera and/or cerebrospinal fluid (CSF) from two groups of PANDAS cases (N=25 first group and N=35 second group), sera from Tourette's syndrome (N=18), obsessive-compulsive disorder (N=25), attention deficit hyperactivity disorder (N=18), and healthy controls (N=28) by direct enzyme-linked immunosorbent assay (ELISA). IgG specific for neuronal autoantigens was significantly elevated during the acute symptomatic phase, and the activity of calcium/calmodulin-dependent protein kinase II (CaMKII) pathway was significantly elevated in human neuronal cells. Five assays confirmed the disease in SC and in two groups of children with PANDAS. In 35 acute onset PANDAS patients, 32 sera (91.4%) were positive for one or more of the anti-neuronal autoantibodies compared with 9 of 28 healthy controls (32.1%, p<0.0001). Importantly, CSF of 32 (91.4%) PANDAS patients had one or more detectable anti-neuronal autoantibody titers and CaMKII activation. Among healthy control subjects with elevated serum autoantibody titers for individual antigens, none (0%) were positively associated with elevated positive CaMKII activation, which was a striking contrast to the sera of PANDAS subjects, who had 76–89% positive association with elevated individual autoantibody titers and positive CaMKII activity. At 6 months follow-up, symptoms improved for more than 80% of PANDAS subjects, and serum autoantibody titers also significantly decreased. Results reported herein and previously published studies in our laboratory suggest the antibody biomarkers may be a useful adjunct to clinical diagnosis of SC, PANDAS, and related disorders and are the first known group of autoantibodies detecting dopamine receptor-mediated encephalitis in children. Frontiers Media S.A. 2020-06-24 /pmc/articles/PMC7328706/ /pubmed/32670106 http://dx.doi.org/10.3389/fpsyt.2020.00564 Text en Copyright © 2020 Chain, Alvarez, Mascaro-Blanco, Reim, Bentley, Hommer, Grant, Leckman, Kawikova, Williams, Stoner, Swedo and Cunningham http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Psychiatry
Chain, Jennifer L.
Alvarez, Kathy
Mascaro-Blanco, Adita
Reim, Sean
Bentley, Rebecca
Hommer, Rebecca
Grant, Paul
Leckman, James F.
Kawikova, Ivana
Williams, Kyle
Stoner, Julie A.
Swedo, Susan E.
Cunningham, Madeleine W.
Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections
title Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections
title_full Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections
title_fullStr Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections
title_full_unstemmed Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections
title_short Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections
title_sort autoantibody biomarkers for basal ganglia encephalitis in sydenham chorea and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328706/
https://www.ncbi.nlm.nih.gov/pubmed/32670106
http://dx.doi.org/10.3389/fpsyt.2020.00564
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