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Disease specificity of autoantibodies to cytosolic 5'-nucleotidase 1A in sporadic inclusion body myositis versus known autoimmune diseases

MK. Herbert, J. Stammen-Vogelzangs, MM. Verbeek, A. Rietveld, IE. Lundberg, H. Chinoy, JA. Lamb, RG. Cooper, M. Roberts, UA. Badrising, JL. De Bleecker, PM. Machado, MG. Hanna, L. Plestilova, J. Vencovsky, BG. van Engelen, GJ. Pruijn,

. 2016 ; 75 (4) : 696-701. [pub] 20150224

Language English Country England, Great Britain

Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc16028484

OBJECTIVES: The diagnosis of inclusion body myositis (IBM) can be challenging as it can be difficult to clinically distinguish from other forms of myositis, particularly polymyositis (PM). Recent studies have shown frequent presence of autoantibodies directed against cytosolic 5'-nucleotidase 1A (cN-1A) in patients with IBM. We therefore, examined the autoantigenicity and disease specificity of major epitopes of cN-1A in patients with sporadic IBM compared with healthy and disease controls. METHODS: Serum samples obtained from patients with IBM (n=238), PM and dermatomyositis (DM) (n=185), other autoimmune diseases (n=246), other neuromuscular diseases (n=93) and healthy controls (n=35) were analysed for the presence of autoantibodies using immunodominant cN-1A peptide ELISAs. RESULTS: Autoantibodies directed against major epitopes of cN-1A were frequent in patients with IBM (37%) but not in PM, DM or non-autoimmune neuromuscular diseases (<5%). Anti-cN-1A reactivity was also observed in some other autoimmune diseases, particularly Sjögren's syndrome (SjS; 36%) and systemic lupus erythematosus (SLE; 20%). CONCLUSIONS: In summary, we found frequent anti-cN-1A autoantibodies in sera from patients with IBM. Heterogeneity in reactivity with the three immunodominant epitopes indicates that serological assays should not be limited to a distinct epitope region. The similar reactivities observed for SjS and SLE demonstrate the need to further investigate whether distinct IBM-specific epitopes exist.

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$a Herbert, Megan K $u Department of Biomolecular Chemistry, Radboud Institute for Molecular Life Sciences and Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands.
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$a OBJECTIVES: The diagnosis of inclusion body myositis (IBM) can be challenging as it can be difficult to clinically distinguish from other forms of myositis, particularly polymyositis (PM). Recent studies have shown frequent presence of autoantibodies directed against cytosolic 5'-nucleotidase 1A (cN-1A) in patients with IBM. We therefore, examined the autoantigenicity and disease specificity of major epitopes of cN-1A in patients with sporadic IBM compared with healthy and disease controls. METHODS: Serum samples obtained from patients with IBM (n=238), PM and dermatomyositis (DM) (n=185), other autoimmune diseases (n=246), other neuromuscular diseases (n=93) and healthy controls (n=35) were analysed for the presence of autoantibodies using immunodominant cN-1A peptide ELISAs. RESULTS: Autoantibodies directed against major epitopes of cN-1A were frequent in patients with IBM (37%) but not in PM, DM or non-autoimmune neuromuscular diseases (<5%). Anti-cN-1A reactivity was also observed in some other autoimmune diseases, particularly Sjögren's syndrome (SjS; 36%) and systemic lupus erythematosus (SLE; 20%). CONCLUSIONS: In summary, we found frequent anti-cN-1A autoantibodies in sera from patients with IBM. Heterogeneity in reactivity with the three immunodominant epitopes indicates that serological assays should not be limited to a distinct epitope region. The similar reactivities observed for SjS and SLE demonstrate the need to further investigate whether distinct IBM-specific epitopes exist.
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$a Stammen-Vogelzangs, Judith $u Department of Biomolecular Chemistry, Radboud Institute for Molecular Life Sciences and Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands.
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$a Verbeek, Marcel M $u Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
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$a Rietveld, Anke $u Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.
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$a Lundberg, Ingrid E $u Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden.
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$a Chinoy, Hector $u Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
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$a Lamb, Janine A $u Centre for Integrated Genomic Medical Research, The University of Manchester, Manchester, UK.
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$a Cooper, Robert G $u Faculty of Health & Life Sciences, MRC/ARUK Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
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$a Roberts, Mark $u Salford Royal NHS Foundation Trust, Manchester, UK.
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$a Badrising, Umesh A $u Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
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$a De Bleecker, Jan L $u Department of Neurology, Neuromuscular Reference Centre, Ghent University Hospital, Ghent, Belgium.
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$a Machado, Pedro M $u MRC Centre for Neuromuscular Diseases, University College London, London, UK.
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$a Hanna, Michael G $u MRC Centre for Neuromuscular Diseases, University College London, London, UK.
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$a Plestilova, Lenka $u Department of Rheumatology, First Faculty of Medicine, Institute of Rheumatology, Charles University, Prague, Czech Republic.
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$a Vencovsky, Jiri $u Department of Rheumatology, First Faculty of Medicine, Institute of Rheumatology, Charles University, Prague, Czech Republic.
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$a van Engelen, Baziel G $u Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.
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$a Pruijn, Ger J M $u Department of Biomolecular Chemistry, Radboud Institute for Molecular Life Sciences and Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands.
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