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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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/8/4424 |
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| author | Nicole Hartwig Trier Niccolo Valdarnini Ilaria Fanelli Paolo Rovero Paul Robert Hansen Claus Schafer-Nielsen Evaldas Ciplys Rimantas Slibinskas Flemming Pociot Tina Friis Gunnar Houen |
| author_facet | Nicole Hartwig Trier Niccolo Valdarnini Ilaria Fanelli Paolo Rovero Paul Robert Hansen Claus Schafer-Nielsen Evaldas Ciplys Rimantas Slibinskas Flemming Pociot Tina Friis Gunnar Houen |
| author_sort | Nicole Hartwig Trier |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T04:33:57Z |
| format | Article |
| id | doaj.art-6bb111ad79b54c279d559b26a90c32e5 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:33:57Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6bb111ad79b54c279d559b26a90c32e52023-12-03T13:30:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01238442410.3390/ijms23084424Peptide Antibody Reactivity to Homologous Regions in Glutamate Decarboxylase Isoforms and Coxsackievirus B4 P2CNicole Hartwig Trier0Niccolo Valdarnini1Ilaria Fanelli2Paolo Rovero3Paul Robert Hansen4Claus Schafer-Nielsen5Evaldas Ciplys6Rimantas Slibinskas7Flemming Pociot8Tina Friis9Gunnar Houen10Department of Neurology, Rigshospitalet Glostrup, Valdemar Hansens vej 13, 2600 Glostrup, DenmarkInterdepartmental Laboratory of Peptide and Protein Chemistry and Biology, Department of NeuroFarBa, University of Florence, Via Ugo Schiff 6, I-50019 Sesto Fiorentino, ItalyInterdepartmental Laboratory of Peptide and Protein Chemistry and Biology, Department of NeuroFarBa, University of Florence, Via Ugo Schiff 6, I-50019 Sesto Fiorentino, ItalyInterdepartmental Laboratory of Peptide and Protein Chemistry and Biology, Department of NeuroFarBa, University of Florence, Via Ugo Schiff 6, I-50019 Sesto Fiorentino, ItalyDepartment of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, DenmarkSchafer-N, Lersø Parkallé 42, 2100 Copenhagen, DenmarkLife Sciences Center, Institute of Biotechnology, Vilnius University, Saulėtekio al. 7, LT-10257 Vilnius, LithuaniaLife Sciences Center, Institute of Biotechnology, Vilnius University, Saulėtekio al. 7, LT-10257 Vilnius, LithuaniaSteno Diabetes Center, Borgmester Ib Juuls Vej 83, 2730 Hellerup, DenmarkDepartment of Autoimmunity and Biomarkers, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, DenmarkDepartment of Neurology, Rigshospitalet Glostrup, Valdemar Hansens vej 13, 2600 Glostrup, DenmarkTwo 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.https://www.mdpi.com/1422-0067/23/8/4424antibody cross-reactivitycoxsackievirusglutamate decarboxylasepeptide antibodiesstiff-person syndrometype 1 diabetes |
| spellingShingle | Nicole Hartwig Trier Niccolo Valdarnini Ilaria Fanelli Paolo Rovero Paul Robert Hansen Claus Schafer-Nielsen Evaldas Ciplys Rimantas Slibinskas Flemming Pociot Tina Friis Gunnar Houen Peptide Antibody Reactivity to Homologous Regions in Glutamate Decarboxylase Isoforms and Coxsackievirus B4 P2C International Journal of Molecular Sciences antibody cross-reactivity coxsackievirus glutamate decarboxylase peptide antibodies stiff-person syndrome type 1 diabetes |
| 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 | antibody cross-reactivity coxsackievirus glutamate decarboxylase peptide antibodies stiff-person syndrome type 1 diabetes |
| url | https://www.mdpi.com/1422-0067/23/8/4424 |
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