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Arthritis & rheumatology (Hoboken, N.J.) · 2026

Plasma Proteome Reflects Tissue Damage and Clinical Manifestations in Patients With Inflammatory Myopathies.

СтатьяНазвание и аннотация: Перевод в очереди
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Luo Yue-Bei, Kenrick Josefin, Galindo-Feria Angeles S, Notarnicola Antonella, Navas Ana Daniela Ulloa, Peralta-Garcia Irene, Demuynck Orane, Kemp Andrea, Leclair Valérie, Lodin Karin, Van Gompel Eveline, Dani Lara, Espinosa-Ortega Fabricio, Dastmalchi Maryam, Padyukov Leonid, Preger Charlotta, Álvez María Bueno, Uhlén Mathias, Nilsson Peter, Edfors Fredrik, Diaz-Gallo Lina-Marcela, Pin Elisa, Lundberg Ingrid E, Horuluoglu Begum

Аннотация

OBJECTIVE: Tissue-specific biomarkers that are reliable and associated with clinical manifestations of idiopathic inflammatory myopathy (IIM) are lacking. The blood circulation in individuals serves as a central conduit, allowing communication between tissues and facilitating clearance and recycling of tissue-derived proteins. Thus, we applied a dual antibody-based proximity extension assay to profile >1,000 proteins in subtypes of patients with IIM.

METHODS: Plasma samples from 201 patients diagnosed with IIM at Karolinska University Hospital were analyzed using Olink Proximity Extension Assay technology. Clinical manifestations, disease activity measurements, and laboratory test results were collected. First, we evaluated differential protein abundance across IIM subtypes. Then we calculated tissue scores for each disease subtype using tissue gene expression databases. Finally, interferon (IFN) pathway scores were calculated.

RESULTS: Plasma from patients with dermatomyositis was enriched for IFN signaling and skin-associated proteins, antisynthetase syndrome (ASyS) for lung-associated proteins, immune-mediated necrotizing myopathy (IMNM) for muscle-associated proteins, and inclusion body myositis for T cell-response proteins. Patients with IMNM showed the highest tissue score for skeletal muscles, and patients with ASyS showed the highest lung tissue scores. Skeletal muscle scores correlated strongly with muscle disease activity visual analog scale scores, creatine kinase levels, and muscle weakness score. Patients with interstitial lung disease along with anti-MDA5 and those with anti-Jo1 autoantibodies showed differential enrichment of surfactant proteins and IFN pathway activation.

CONCLUSION: Circulatory proteome is a promising tool to capture distinct tissue-specific responses that correlate with disease activity and tissue injury in patients with IIM.