Megan K Herbert1, Judith Stammen-Vogelzangs1, Marcel M Verbeek2, Anke Rietveld3, Ingrid E Lundberg4, Hector Chinoy5, Janine A Lamb6, Robert G Cooper7, Mark Roberts8, Umesh A Badrising9, Jan L De Bleecker10, Pedro M Machado11, Michael G Hanna11, Lenka Plestilova12, Jiri Vencovsky12, Baziel G van Engelen3, Ger J M Pruijn1. 1. Department of Biomolecular Chemistry, Radboud Institute for Molecular Life Sciences and Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands. 2. 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. 3. Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands. 4. Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden. 5. Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK. 6. Centre for Integrated Genomic Medical Research, The University of Manchester, Manchester, UK. 7. Faculty of Health & Life Sciences, MRC/ARUK Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK. 8. Salford Royal NHS Foundation Trust, Manchester, UK. 9. Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands. 10. Department of Neurology, Neuromuscular Reference Centre, Ghent University Hospital, Ghent, Belgium. 11. MRC Centre for Neuromuscular Diseases, University College London, London, UK. 12. Department of Rheumatology, First Faculty of Medicine, Institute of Rheumatology, Charles University, Prague, Czech Republic.
Abstract
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Authors: Fieke M Cox; Maarten J Titulaer; Jacob K Sont; Axel R Wintzen; Jan J G M Verschuuren; Umesh A Badrising Journal: Brain Date: 2011-09-09 Impact factor: 13.501
Authors: G J D Hengstman; R Brouwer; W T M Vree Egberts; H P Seelig; P J H Jongen; W J van Venrooij; B G van Engelen Journal: J Neurol Date: 2002-01 Impact factor: 4.849
Authors: Umesh A Badrising; Marion L C Maat-Schieman; Johannes C van Houwelingen; Peter A van Doorn; Sjoerd G van Duinen; Baziel G M van Engelen; Carin G Faber; Jessica E Hoogendijk; Aeiko E de Jager; Peter J Koehler; Marianne de Visser; Jan J G M Verschuuren; Axel R Wintzen Journal: J Neurol Date: 2005-06-17 Impact factor: 4.849
Authors: Helma Pluk; Bas J A van Hoeve; Sander H J van Dooren; Judith Stammen-Vogelzangs; Annemarie van der Heijden; Helenius J Schelhaas; Marcel M Verbeek; Umesh A Badrising; Snjolaug Arnardottir; Karina Gheorghe; Ingrid E Lundberg; Wilbert C Boelens; Baziel G van Engelen; Ger J M Pruijn Journal: Ann Neurol Date: 2013-03-04 Impact factor: 10.422
Authors: Richard M Yeker; Iago Pinal-Fernandez; Lisa G Rider; Andrew L Mammen; Takayuki Kishi; Katherine Pak; Ira N Targoff; Frederick W Miller Journal: Ann Rheum Dis Date: 2018-01-23 Impact factor: 19.103
Authors: Anke Rietveld; Judith Wienke; Eline Visser; Wilma Vree Egberts; Wolfgang Schlumberger; Baziel van Engelen; Annet van Royen-Kerkhof; Hui Lu; Lucy Wedderburn; Christiaan Saris; Sarah Tansley; Ger Pruijn Journal: Arthritis Rheumatol Date: 2021-05-18 Impact factor: 10.995