Your browser doesn't support javascript.
loading
Transcriptional derepression of CHD4/NuRD-regulated genes in the muscle of patients with dermatomyositis and anti-Mi2 autoantibodies.
Pinal-Fernandez, Iago; Milisenda, Jose Cesar; Pak, Katherine; Muñoz-Braceras, Sandra; Casal-Dominguez, Maria; Torres-Ruiz, Jiram; Dell'Orso, Stefania; Naz, Faiza; Gutierrez-Cruz, Gustavo; Duque-Jaimez, Yaiza; Matas-Garcia, Ana; Padrosa, Joan; Garcia-Garcia, Francesc J; Guitart-Mampel, Mariona; Garrabou, Gloria; Trallero-Araguás, Ernesto; Walitt, Brian; Paik, Julie J; Albayda, Jemima; Christopher-Stine, Lisa; Lloyd, Thomas E; Grau-Junyent, Josep Maria; Selva-O'Callaghan, Albert; Mammen, Andrew Lee.
Afiliación
  • Pinal-Fernandez I; Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA iago.pinalfernandez@nih.gov andrew.mammen@nih.gov.
  • Milisenda JC; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Pak K; Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Muñoz-Braceras S; Muscle Research Unit, Internal Medicine Service, Hospital Clinic, Barcelona, Spain.
  • Casal-Dominguez M; Barcelona University, Barcelona, Spain.
  • Torres-Ruiz J; CIBERER, Barcelona, Spain.
  • Dell'Orso S; Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Naz F; Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Gutierrez-Cruz G; Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Duque-Jaimez Y; Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Matas-Garcia A; Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
  • Padrosa J; Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Garcia-Garcia FJ; Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Guitart-Mampel M; Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Garrabou G; Muscle Research Unit, Internal Medicine Service, Hospital Clinic, Barcelona, Spain.
  • Trallero-Araguás E; Muscle Research Unit, Internal Medicine Service, Hospital Clinic, Barcelona, Spain.
  • Walitt B; Barcelona University, Barcelona, Spain.
  • Paik JJ; CIBERER, Barcelona, Spain.
  • Albayda J; CIBERER, Barcelona, Spain.
  • Christopher-Stine L; Muscle Research Unit, Internal Medicine Service, Hospital Clinic, Barcelona, Spain.
  • Lloyd TE; Barcelona University, Barcelona, Spain.
  • Grau-Junyent JM; CIBERER, Barcelona, Spain.
  • Selva-O'Callaghan A; Muscle Research Unit, Internal Medicine Service, Hospital Clinic, Barcelona, Spain.
  • Mammen AL; Barcelona University, Barcelona, Spain.
Ann Rheum Dis ; 82(8): 1091-1097, 2023 08.
Article en En | MEDLINE | ID: mdl-37130727
OBJECTIVES: Myositis is a heterogeneous family of diseases including dermatomyositis (DM), immune-mediated necrotising myopathy (IMNM), antisynthetase syndrome (AS) and inclusion body myositis (IBM). Myositis-specific autoantibodies define different subtypes of myositis. For example, patients with anti-Mi2 autoantibodies targeting the chromodomain helicase DNA-binding protein 4 (CHD4)/NuRD complex (a transcriptional repressor) have more severe muscle disease than other DM patients. This study aimed to define the transcriptional profile of muscle biopsies from anti-Mi2-positive DM patients. METHODS: RNA sequencing was performed on muscle biopsies (n=171) from patients with anti-Mi2-positive DM (n=18), DM without anti-Mi2 autoantibodies (n=32), AS (n=18), IMNM (n=54) and IBM (n=16) as well as 33 normal muscle biopsies. Genes specifically upregulated in anti-Mi2-positive DM were identified. Muscle biopsies were stained for human immunoglobulin and protein products corresponding to genes specifically upregulated in anti-Mi2-positive muscle biopsies. RESULTS: A set of 135 genes, including SCRT1 and MADCAM1, was specifically overexpressed in anti-Mi2-positive DM muscle. This set was enriched for CHD4/NuRD-regulated genes and included genes that are not otherwise expressed in skeletal muscle. The expression levels of these genes correlated with anti-Mi2 autoantibody titres, markers of disease activity and with the other members of the gene set. In anti-Mi2-positive muscle biopsies, immunoglobulin was localised to the myonuclei, MAdCAM-1 protein was present in the cytoplasm of perifascicular fibres, and SCRT1 protein was localised to myofibre nuclei. CONCLUSIONS: Based on these findings, we hypothesise that anti-Mi2 autoantibodies could exert a pathogenic effect by entering damaged myofibres, inhibiting the CHD4/NuRD complex, and subsequently derepressing the unique set of genes defined in this study.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Autoinmunes / Miositis por Cuerpos de Inclusión / Dermatomiositis / Miositis Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Ann Rheum Dis Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Autoinmunes / Miositis por Cuerpos de Inclusión / Dermatomiositis / Miositis Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Ann Rheum Dis Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido