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Peptide Antibody Reactivity to Homologous Regions in Glutamate Decarboxylase Isoforms and Coxsackievirus B4 P2C

Two isoforms of the glutamate decarboxylase (GAD) enzyme exist, GAD65 and GAD67, which are associated with type 1 diabetes (T1D) and stiff-person syndrome (SPS), respectively. Interestingly, it has been reported that T1D patients seldom develop SPS, whereas patients with SPS occasionally develop T1D...

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Autores principales: Trier, Nicole Hartwig, Valdarnini, Niccolo, Fanelli, Ilaria, Rovero, Paolo, Hansen, Paul Robert, Schafer-Nielsen, Claus, Ciplys, Evaldas, Slibinskas, Rimantas, Pociot, Flemming, Friis, Tina, Houen, Gunnar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028130/
https://www.ncbi.nlm.nih.gov/pubmed/35457242
http://dx.doi.org/10.3390/ijms23084424
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author Trier, Nicole Hartwig
Valdarnini, Niccolo
Fanelli, Ilaria
Rovero, Paolo
Hansen, Paul Robert
Schafer-Nielsen, Claus
Ciplys, Evaldas
Slibinskas, Rimantas
Pociot, Flemming
Friis, Tina
Houen, Gunnar
author_facet Trier, Nicole Hartwig
Valdarnini, Niccolo
Fanelli, Ilaria
Rovero, Paolo
Hansen, Paul Robert
Schafer-Nielsen, Claus
Ciplys, Evaldas
Slibinskas, Rimantas
Pociot, Flemming
Friis, Tina
Houen, Gunnar
author_sort Trier, Nicole Hartwig
collection PubMed
description Two isoforms of the glutamate decarboxylase (GAD) enzyme exist, GAD65 and GAD67, which are associated with type 1 diabetes (T1D) and stiff-person syndrome (SPS), respectively. Interestingly, it has been reported that T1D patients seldom develop SPS, whereas patients with SPS occasionally develop T1D. In addition, coxsackievirus B4 (CVB4) has previously been proposed to be involved in the onset of T1D through molecular mimicry. On this basis, we aimed to examine antibody cross-reactivity between a specific region of GAD65 and GAD67, which has high sequence homology to the nonstructural P2C protein of CVB4 to determine potential correlations at antibody level. Monoclonal peptide antibodies generated in mice specific for a region with high similarity in all three proteins were screened for reactivity along with human sera in immunoassays. In total, six antibodies were generated. Two of the antibodies reacted to both GAD isoforms. However, none of the antibodies were cross-reactive to CVB, suggesting that antibody cross-reactivity between GAD65 and CVB, and GAD67 and CVB may not contribute to the onset of T1D and SPS, respectively.
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spelling pubmed-90281302022-04-23 Peptide Antibody Reactivity to Homologous Regions in Glutamate Decarboxylase Isoforms and Coxsackievirus B4 P2C Trier, Nicole Hartwig Valdarnini, Niccolo Fanelli, Ilaria Rovero, Paolo Hansen, Paul Robert Schafer-Nielsen, Claus Ciplys, Evaldas Slibinskas, Rimantas Pociot, Flemming Friis, Tina Houen, Gunnar Int J Mol Sci Article Two isoforms of the glutamate decarboxylase (GAD) enzyme exist, GAD65 and GAD67, which are associated with type 1 diabetes (T1D) and stiff-person syndrome (SPS), respectively. Interestingly, it has been reported that T1D patients seldom develop SPS, whereas patients with SPS occasionally develop T1D. In addition, coxsackievirus B4 (CVB4) has previously been proposed to be involved in the onset of T1D through molecular mimicry. On this basis, we aimed to examine antibody cross-reactivity between a specific region of GAD65 and GAD67, which has high sequence homology to the nonstructural P2C protein of CVB4 to determine potential correlations at antibody level. Monoclonal peptide antibodies generated in mice specific for a region with high similarity in all three proteins were screened for reactivity along with human sera in immunoassays. In total, six antibodies were generated. Two of the antibodies reacted to both GAD isoforms. However, none of the antibodies were cross-reactive to CVB, suggesting that antibody cross-reactivity between GAD65 and CVB, and GAD67 and CVB may not contribute to the onset of T1D and SPS, respectively. MDPI 2022-04-17 /pmc/articles/PMC9028130/ /pubmed/35457242 http://dx.doi.org/10.3390/ijms23084424 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Trier, Nicole Hartwig
Valdarnini, Niccolo
Fanelli, Ilaria
Rovero, Paolo
Hansen, Paul Robert
Schafer-Nielsen, Claus
Ciplys, Evaldas
Slibinskas, Rimantas
Pociot, Flemming
Friis, Tina
Houen, Gunnar
Peptide Antibody Reactivity to Homologous Regions in Glutamate Decarboxylase Isoforms and Coxsackievirus B4 P2C
title Peptide Antibody Reactivity to Homologous Regions in Glutamate Decarboxylase Isoforms and Coxsackievirus B4 P2C
title_full Peptide Antibody Reactivity to Homologous Regions in Glutamate Decarboxylase Isoforms and Coxsackievirus B4 P2C
title_fullStr Peptide Antibody Reactivity to Homologous Regions in Glutamate Decarboxylase Isoforms and Coxsackievirus B4 P2C
title_full_unstemmed Peptide Antibody Reactivity to Homologous Regions in Glutamate Decarboxylase Isoforms and Coxsackievirus B4 P2C
title_short Peptide Antibody Reactivity to Homologous Regions in Glutamate Decarboxylase Isoforms and Coxsackievirus B4 P2C
title_sort peptide antibody reactivity to homologous regions in glutamate decarboxylase isoforms and coxsackievirus b4 p2c
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028130/
https://www.ncbi.nlm.nih.gov/pubmed/35457242
http://dx.doi.org/10.3390/ijms23084424
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