Document Detail


Enteroviruses and the pathogenesis of type 1 diabetes revisited: cross-reactivity of enterovirus capsid protein (VP1) antibodies with human mitochondrial proteins.
MedLine Citation:
PMID:  23335350     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Current or recent enteroviral infections show an association with type 1 diabetes. However, evidence for this has mainly been generated using a particular mouse monoclonal antibody (clone 5-D8/1) which binds the viral capsid protein VP1. Difficulty in confirming these findings using other independent methods has led to the concern that this might be artefactual. To address this, we examined the potential cross-reactivity of clone 5-D8/1 with normal islet proteins. Western blotting, two-dimensional gel electrophoresis, and mass spectrometry were used to identify human islet proteins bound by the clone 5-D8/1. We found a distinct reactivity with two mitochondrial proteins, creatine kinase B-type and ATP synthase beta subunit. Immunohistochemistry using the clone 5-D8/1 revealed a granular cytoplasmic staining pattern in mitochondria-rich cells, ie hepatocytes, ductal epithelial cells, vascular endothelial cells, skeletal muscle cells, and the neoplastic salivary gland oncocytoma cells, whereas connective tissue and infiltrating immune cells were negative. Staining on islets of Langerhans from subjects with recent-onset type 1 diabetes, but not on isolated human islets infected in vitro with enteroviruses, could be blocked after mixing the clone 5-D8/1 with the mitochondrial proteins. Collectively, our data show that the clone 5-D8/1 detects two human mitochondrial enzymes in addition to enteroviral VP1. The notion that the previously reported VP1 positivity in islets of recent-onset type 1 diabetes patients could reflect cross-reactivity to native islet proteins and not the presence of EV is supported by difficulties in demonstrating EV infection by independent techniques such as PCR or in situ hybridization. These findings call for revisiting the presence of enteroviruses in pancreatic islets of patients with type 1 diabetes.
Authors:
Sara F Hansson; Stella Korsgren; Fredrik Pontén; Olle Korsgren
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pathology     Volume:  229     ISSN:  1096-9896     ISO Abbreviation:  J. Pathol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-15     Completed Date:  2013-05-02     Revised Date:  2013-05-22    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  719-28     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Affiliation:
Proteomics Core Facility, University of Gothenburg, Gothenburg, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Antibodies / immunology*
Artifacts
Blotting, Western
Capsid Proteins / immunology*
Creatine Kinase / immunology*
Cross Reactions
Diabetes Mellitus, Type 1 / enzymology,  immunology*,  virology
Electrophoresis, Gel, Two-Dimensional
Enterovirus / immunology*
Enterovirus Infections / complications,  immunology*,  virology
Humans
Immunohistochemistry
Islets of Langerhans / enzymology,  immunology*,  virology
Mitochondrial Proton-Translocating ATPases / immunology*
Proteomics / methods
Reproducibility of Results
Tandem Mass Spectrometry
Tissue Culture Techniques
Chemical
Reg. No./Substance:
0/Antibodies; 0/Capsid Proteins; EC 2.7.3.2/Creatine Kinase; EC 3.6.3.-/Mitochondrial Proton-Translocating ATPases; EC 3.6.3.14/ATP5B protein, human
Comments/Corrections
Comment In:
J Pathol. 2013 May;230(1):1-3   [PMID:  23389883 ]

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