Transcriptomic profiling reveals distinct subsets of immune checkpoint inhibitor induced myositis
Authors' conclusion
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.
Study context
- Population
- Muscle biopsies from patients with ICI-myositis, other myositis types and normal muscle
- Participants
- 200 muscle biopsies
- Comparison
- Muscle biopsy gene expression in ICI-myositis vs dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotising myopathy (IMNM), inclusion body myositis (IBM) and normal muscle
- ICI-myositisn = 35
- DMn = 44
- ASn = 18
- IMNMn = 54
- IBMn = 16
- Normal musclen = 33reference
- Outcome
- Gene expression patterns in muscle biopsies from patients with ICI-myositis
Methodological detailsbulk RNA sequencing, single nuclei RNA sequencing, unsupervised clustering, Single nuclei RNA sequencing on 22 muscle biopsies (seven ICI-myositis, four DM, three AS, six IMNM, two IBM)
- Bulk RNA sequencing
- Single nuclei RNA sequencing
- Unsupervised clustering
- Single nuclei RNA sequencing on 22 muscle biopsies (seven ICI-myositis, four DM, three AS, six IMNM, two IBM)
Main finding
As reported in the abstract
Transcriptomic subsets of ICI-myositis
- Unsupervised clustering defined three distinct transcriptomic subsets: ICI-DM, ICI-MYO1 and ICI-MYO2
- ICI-DM: patients with DM and anti-TIF1γ autoantibodies who, like DM patients, overexpressed type 1 IFN-inducible genes
- ICI-MYO1: highly inflammatory muscle biopsies; included all patients who developed coexisting myocarditis
- ICI-MYO2: predominant necrotising pathology and low muscle inflammation
- Type 2 IFN pathway activated in both ICI-DM and ICI-MYO1
- Unlike other myositis types, all three ICI-myositis subsets overexpressed IL6 pathway genes
Original publication
Transcriptomic profiling reveals distinct subsets of immune checkpoint inhibitor induced myositis. Ann Rheum Dis. Published 17 February 2023. doi:10.
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