RT Journal Article
SR Electronic
T1 Transcriptomic profiling reveals distinct subsets of immune checkpoint inhibitor induced myositis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 829
OP 836
DO 10.1136/ard-2022-223792
VO 82
IS 6
A1 Iago Pinal-Fernandez
A1 Angela Quintana
A1 Jose Cesar Milisenda
A1 Maria Casal-Dominguez
A1 Sandra Muñoz-Braceras
A1 Assia Derfoul
A1 Jiram Torres-Ruiz
A1 Katherine Pak
A1 Stefania Dell'Orso
A1 Faiza Naz
A1 Gustavo Gutierrez-Cruz
A1 Margherita Milone
A1 Shahar Shelly
A1 Yaiza Duque-Jaimez
A1 Ester Tobias-Baraja
A1 Ana Matas-Garcia
A1 Gloria Garrabou
A1 Joan Padrosa
A1 Javier Ros
A1 Ernesto Trallero-Araguás
A1 Brian Walitt
A1 Lisa Christopher-Stine
A1 Thomas E Lloyd
A1 Chen Zhao
A1 Shannon Swift
A1 Arun Rajan
A1 Josep Maria Grau-Junyent
A1 Albert Selva-O'Callaghan
A1 Teerin Liewluck
A1 Andrew Lee Mammen
YR 2023
UL http://ard.bmj.com/content/82/6/829.abstract
AB 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.