Transcriptomic profiling reveals distinct subsets of immune checkpoint inhibitor induced myositis
| Autor: | Iago Pinal-Fernandez, Angela Quintana, Jose Cesar Milisenda, Maria Casal-Dominguez, Sandra Muñoz-Braceras, Assia Derfoul, Jiram Torres-Ruiz, Katherine Pak, Stefania Dell'Orso, Faiza Naz, Gustavo Gutierrez-Cruz, Margherita Milone, Shahar Shelly, Yaiza Duque-Jaimez, Ester Tobias-Baraja, Ana Matas-Garcia, Gloria Garrabou, Joan Padrosa, Javier Ros, Ernesto Trallero-Araguás, Brian Walitt, Lisa Christopher-Stine, Thomas E Lloyd, Chen Zhao, Shannon Swift, Arun Rajan, Josep Maria Grau-Junyent, Albert Selva-O'Callaghan, Teerin Liewluck, Andrew Lee Mammen |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Annals of the Rheumatic Diseases. 82:829-836 |
| ISSN: | 1468-2060 0003-4967 |
| Popis: | ObjectivesInflammatory myopathy or myositis is a heterogeneous family of immune-mediated diseases including dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Immune checkpoint inhibitors (ICIs) can also cause myositis (ICI-myositis). This study was designed to define gene expression patterns in muscle biopsies from patients with ICI-myositis.MethodsBulk RNA sequencing was performed on 200 muscle biopsies (35 ICI-myositis, 44 DM, 18 AS, 54 IMNM, 16 IBM and 33 normal muscle biopsies) and single nuclei RNA sequencing was performed on 22 muscle biopsies (seven ICI-myositis, four DM, three AS, six IMNM and two IBM).ResultsUnsupervised clustering defined three distinct transcriptomic subsets of ICI-myositis: ICI-DM, ICI-MYO1 and ICI-MYO2. ICI-DM included patients with DM and anti-TIF1γ autoantibodies who, like DM patients, overexpressed type 1 interferon-inducible genes. ICI-MYO1 patients had highly inflammatory muscle biopsies and included all patients that developed coexisting myocarditis. ICI-MYO2 was composed of patients with predominant necrotising pathology and low levels of muscle inflammation. The type 2 interferon pathway was activated both in ICI-DM and ICI-MYO1. Unlike the other types of myositis, all three subsets of ICI-myositis patients overexpressed genes involved in the IL6 pathway.ConclusionsWe identified three distinct types of ICI-myositis based on transcriptomic analyses. The IL6 pathway was overexpressed in all groups, the type I interferon pathway activation was specific for ICI-DM, the type 2 IFN pathway was overexpressed in both ICI-DM and ICI-MYO1 and only ICI-MYO1 patients developed myocarditis. |
| Databáze: | OpenAIRE |
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