TY - JOUR T1 - Transcriptomic profiling reveals distinct subsets of immune checkpoint inhibitor induced myositis JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 829 LP - 836 DO - 10.1136/ard-2022-223792 VL - 82 IS - 6 AU - Iago Pinal-Fernandez AU - Angela Quintana AU - Jose Cesar Milisenda AU - Maria Casal-Dominguez AU - Sandra Muñoz-Braceras AU - Assia Derfoul AU - Jiram Torres-Ruiz AU - Katherine Pak AU - Stefania Dell'Orso AU - Faiza Naz AU - Gustavo Gutierrez-Cruz AU - Margherita Milone AU - Shahar Shelly AU - Yaiza Duque-Jaimez AU - Ester Tobias-Baraja AU - Ana Matas-Garcia AU - Gloria Garrabou AU - Joan Padrosa AU - Javier Ros AU - Ernesto Trallero-Araguás AU - Brian Walitt AU - Lisa Christopher-Stine AU - Thomas E Lloyd AU - Chen Zhao AU - Shannon Swift AU - Arun Rajan AU - Josep Maria Grau-Junyent AU - Albert Selva-O'Callaghan AU - Teerin Liewluck AU - Andrew Lee Mammen Y1 - 2023/06/01 UR - http://ard.bmj.com/content/82/6/829.abstract N2 - Objectives Inflammatory 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.Methods Bulk 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).Results Unsupervised 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.Conclusions We 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.Data are available on reasonable request. ER -