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RIG-I expression in perifascicular myofibers is a reliable biomarker of dermatomyositis

BACKGROUND: Dermatomyositis (DM) is inflammatory myopathy or myositis characterized by muscle weakness and skin manifestations. In the differential diagnosis of DM the evaluation of the muscle biopsy is of importance among other parameters. Perifascicular atrophy in the muscle biopsy is considered a...

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Autores principales: Suárez-Calvet, Xavier, Gallardo, Eduard, Pinal-Fernandez, Iago, De Luna, Noemi, Lleixà, Cinta, Díaz-Manera, Jordi, Rojas-García, Ricardo, Castellví, Ivan, Martínez, M. Angeles, Grau, Josep M., Selva-O’Callaghan, Albert, Illa, Isabel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525343/
https://www.ncbi.nlm.nih.gov/pubmed/28738907
http://dx.doi.org/10.1186/s13075-017-1383-0
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author Suárez-Calvet, Xavier
Gallardo, Eduard
Pinal-Fernandez, Iago
De Luna, Noemi
Lleixà, Cinta
Díaz-Manera, Jordi
Rojas-García, Ricardo
Castellví, Ivan
Martínez, M. Angeles
Grau, Josep M.
Selva-O’Callaghan, Albert
Illa, Isabel
author_facet Suárez-Calvet, Xavier
Gallardo, Eduard
Pinal-Fernandez, Iago
De Luna, Noemi
Lleixà, Cinta
Díaz-Manera, Jordi
Rojas-García, Ricardo
Castellví, Ivan
Martínez, M. Angeles
Grau, Josep M.
Selva-O’Callaghan, Albert
Illa, Isabel
author_sort Suárez-Calvet, Xavier
collection PubMed
description BACKGROUND: Dermatomyositis (DM) is inflammatory myopathy or myositis characterized by muscle weakness and skin manifestations. In the differential diagnosis of DM the evaluation of the muscle biopsy is of importance among other parameters. Perifascicular atrophy in the muscle biopsy is considered a hallmark of DM. However, perifascicular atrophy is not observed in all patients with DM and, conversely, perifascicular atrophy can be observed in other myositis such as antisynthetase syndrome (ASS), complicating DM diagnosis. Retinoic acid inducible-gene I (RIG-I), a receptor of innate immunity that promotes type I interferon, was observed in perifascicular areas in DM. We compared the value of RIG-I expression with perifascicular atrophy as a biomarker of DM. METHODS: We studied by immunohistochemical analysis the expression of RIG-I and the presence of perifascicular atrophy in 115 coded muscle biopsies: 44 patients with DM, 18 with myositis with overlap, 8 with ASS, 27 with non-DM inflammatory myopathy (16 with polymyositis, 6 with inclusion body myositis, 5 with immune-mediated necrotizing myopathy), 8 with muscular dystrophy (4 with dysferlinopathy, 4 with fascioscapulohumeral muscle dystrophy) and 10 healthy controls. RESULTS: We found RIG-I-positive fibers in 50% of DM samples vs 11% in non-DM samples (p < 0.001). Interestingly, RIG-I staining identified 32% of DM patients without perifascicular atrophy (p = 0.007). RIG-I sensitivity was higher than perifascicular atrophy (p < 0.001). No differences in specificity between perifascicular atrophy and RIG-I staining were found (92% vs 88%). RIG-I staining was more reproducible than perifascicular atrophy (κ coefficient 0.52 vs 0.37). CONCLUSIONS: The perifascicular pattern of RIG-I expression supports the diagnosis of DM. Of importance for clinical and therapeutic studies, the inclusion of RIG-I in the routine pathological staining of samples in inflammatory myopathy will allow us to gather more homogeneous subgroups of patients in terms of immunopathogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-017-1383-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-55253432017-07-26 RIG-I expression in perifascicular myofibers is a reliable biomarker of dermatomyositis Suárez-Calvet, Xavier Gallardo, Eduard Pinal-Fernandez, Iago De Luna, Noemi Lleixà, Cinta Díaz-Manera, Jordi Rojas-García, Ricardo Castellví, Ivan Martínez, M. Angeles Grau, Josep M. Selva-O’Callaghan, Albert Illa, Isabel Arthritis Res Ther Research Article BACKGROUND: Dermatomyositis (DM) is inflammatory myopathy or myositis characterized by muscle weakness and skin manifestations. In the differential diagnosis of DM the evaluation of the muscle biopsy is of importance among other parameters. Perifascicular atrophy in the muscle biopsy is considered a hallmark of DM. However, perifascicular atrophy is not observed in all patients with DM and, conversely, perifascicular atrophy can be observed in other myositis such as antisynthetase syndrome (ASS), complicating DM diagnosis. Retinoic acid inducible-gene I (RIG-I), a receptor of innate immunity that promotes type I interferon, was observed in perifascicular areas in DM. We compared the value of RIG-I expression with perifascicular atrophy as a biomarker of DM. METHODS: We studied by immunohistochemical analysis the expression of RIG-I and the presence of perifascicular atrophy in 115 coded muscle biopsies: 44 patients with DM, 18 with myositis with overlap, 8 with ASS, 27 with non-DM inflammatory myopathy (16 with polymyositis, 6 with inclusion body myositis, 5 with immune-mediated necrotizing myopathy), 8 with muscular dystrophy (4 with dysferlinopathy, 4 with fascioscapulohumeral muscle dystrophy) and 10 healthy controls. RESULTS: We found RIG-I-positive fibers in 50% of DM samples vs 11% in non-DM samples (p < 0.001). Interestingly, RIG-I staining identified 32% of DM patients without perifascicular atrophy (p = 0.007). RIG-I sensitivity was higher than perifascicular atrophy (p < 0.001). No differences in specificity between perifascicular atrophy and RIG-I staining were found (92% vs 88%). RIG-I staining was more reproducible than perifascicular atrophy (κ coefficient 0.52 vs 0.37). CONCLUSIONS: The perifascicular pattern of RIG-I expression supports the diagnosis of DM. Of importance for clinical and therapeutic studies, the inclusion of RIG-I in the routine pathological staining of samples in inflammatory myopathy will allow us to gather more homogeneous subgroups of patients in terms of immunopathogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-017-1383-0) contains supplementary material, which is available to authorized users. BioMed Central 2017-07-24 2017 /pmc/articles/PMC5525343/ /pubmed/28738907 http://dx.doi.org/10.1186/s13075-017-1383-0 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Suárez-Calvet, Xavier
Gallardo, Eduard
Pinal-Fernandez, Iago
De Luna, Noemi
Lleixà, Cinta
Díaz-Manera, Jordi
Rojas-García, Ricardo
Castellví, Ivan
Martínez, M. Angeles
Grau, Josep M.
Selva-O’Callaghan, Albert
Illa, Isabel
RIG-I expression in perifascicular myofibers is a reliable biomarker of dermatomyositis
title RIG-I expression in perifascicular myofibers is a reliable biomarker of dermatomyositis
title_full RIG-I expression in perifascicular myofibers is a reliable biomarker of dermatomyositis
title_fullStr RIG-I expression in perifascicular myofibers is a reliable biomarker of dermatomyositis
title_full_unstemmed RIG-I expression in perifascicular myofibers is a reliable biomarker of dermatomyositis
title_short RIG-I expression in perifascicular myofibers is a reliable biomarker of dermatomyositis
title_sort rig-i expression in perifascicular myofibers is a reliable biomarker of dermatomyositis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525343/
https://www.ncbi.nlm.nih.gov/pubmed/28738907
http://dx.doi.org/10.1186/s13075-017-1383-0
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