| Title: |
IFN-α levels correlate with muscle disease activity only in juvenile dermatomyositis patients with anti-MDA5+ autoantibodies |
| Authors: |
Moreau, Thomas; Bondet, Vincent; Veldkamp, Saskia; Bletry, Diego; Ramos, Juliette; Villain, Etienne; Ouldali, Naïm; Alyanakan, Marie-Alexandra; Bodemer, Christine; Bonhomme, Samuel; Dingulu, Glory; Dumaine, Cécile; Duong, Ngoc-Bao; Charuel, Jean-Luc; Eveillard, Laurye-Anne; Fournier, Benjamin; Frémond, Marie-Louise; Myositis Consortium, Dutch Juvenile; Kamphuis, Sylvia; Hoppenreijs, Esther; Armbrust, Wineke; van den Berg, J Merlijn; Hissink Muller, Petra; Isapof, Arnaud; Quartier, Pierre; Vinit, Caroline; Welfringer-Morin, Anne; van Royen-Kerkhof, Annet; van Wijk, Femke; Gitiaux, Cyril; Jansen, Marc; Melki, Isabelle; Duffy, Darragh; Bader-Meunier, Brigitte; Rodero, Mathieu P |
| Contributors: |
Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601); Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Immunologie Translationnelle - Translational Immunology lab; Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); University Medical Center Utrecht (UMCU); AP-HP Hôpital universitaire Robert-Debré Paris; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Université Paris Cité (UPCité); Centre de Référence pour les Maladies Rhumatologiques Auto-Immunes et Systémiques CHU Necker (RAISE); Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Centre de référence national des Maladies Génétiques à Expression Cutanée - National Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal Paris; CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Hôpital Robert Debré Paris; Hôpital Robert Debré; Neurogénétique et neuroinflammation = Neurogenetics and neuroinflammation (Equipe Inserm U1163); Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); CHU Trousseau APHP; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Hôpital Jean Verdier AP-HP; DMU MEFADO Département Médico-Universitaire Médecine de l’enfant et de l’adolescent Necker Hospital Enfants-Malades, AP-HP, Paris, France.; Dutch Juvenile Myositis Consortium: Sylvia S M Kamphuis, Esther P A H Hoppenreijs, Wineke Armbrust, J Merlijn van den Berg, Petra C E Hissink Muller; ANR-21-CE17-0025,JDMINF2,Dérégulation de la voie de l'interféron de type I dans la dermatomyosite juvénile: mieux comprendre la physiopathologie pour mieux identifier de nouveaux biomarqueurs pronostiques(2021) |
| Source: |
ISSN: 1462-0324. |
| Publisher Information: |
CCSD; Oxford University Press (OUP) |
| Publication Year: |
2025 |
| Collection: |
Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| Subject Terms: |
myositis-specific auto-antibodies; MDA5; muscle; interferon; juvenile dermatomyositis; [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics; [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity; [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology |
| Description: |
International audience ; Objective: This study aimed to establish the role of myositis-specific antibodies (MSAs) in the association between type I interferon (IFN-I) plasma levels and disease activity in juvenile dermatomyositis (JDM).Methods: We prospectively obtained 400 samples from 101 JDM patients from two independent cohorts. Autoantibody levels were determined for all patients. Muscle activity was assessed using the Childhood-Myositis Assessment Scale (CMAS). Two characterized homebrew digital ELISAs measuring, respectively, all 12 IFN-α subtype protein and IFN-β were used to quantify IFN-I in patient plasma. Receiver operating characteristic (ROC) curve analysis was used to identify IFN-I thresholds associated with CMAS changes. Correlations between IFN-I levels and CMAS were assessed at recruitment using Spearman’s test, and longitudinally using mixed-effects models to account for repeated measures.Results: IFN-α levels were higher in melanoma differentiation-associated gene 5 (MDA5)-positive patients while IFN-β levels were comparable across MSA subgroups. IFN-β was found to be more effective than IFN-α in distinguishing between active and inactive muscle disease, and between severe and non-severe disease status. Over the disease course, we identified IFN-β as a reliable biomarker of muscle disease activity regardless of MSA expression. In contrast, IFN-α levels showed a specific association with CMAS only in MDA5-positive patients.Conclusion: The exclusive association of IFN-α levels with muscle clinical score in anti-MDA5-positive patients suggests a subgroup-specific pathophysiological mechanism. These findings underscore potentially distinct roles for IFN-I subtypes (IFN-α and IFN-β) as circulating biomarkers of muscle disease activity in JDM according to MSA expression. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41105236; PUBMED: 41105236 |
| DOI: |
10.1093/rheumatology/keaf549 |
| Availability: |
https://hal.science/hal-05370892; https://hal.science/hal-05370892v1/document; https://hal.science/hal-05370892v1/file/MoreauTRJetal_Rheumatology_ReviewersComments.pdf; https://doi.org/10.1093/rheumatology/keaf549 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.6205FC61 |
| Database: |
BASE |