Pathological autoantibody internalisation in myositis
Authors' conclusion
This study demonstrates that, in myositis, autoantibodies are internalised into living cells, causing biological effects consistent with the disrupted function of their autoantigen.
Study context
- Population
- Muscle biopsies from patients with myositis, disease controls and healthy controls; cultured myoblasts
- Participants
- 669 samples
- Outcome
- Whether myositis autoantibodies targeting intracellular proteins enter living muscle cells
Methodological detailsconfocal immunofluorescence microscopy, bulk RNA sequencing, electroporation of patient antibodies into cultured myoblasts
- Confocal immunofluorescence microscopy
- Bulk RNA sequencing
- Electroporation of patient antibodies into cultured myoblasts
Main finding
As reported in the abstract
- In patients with myositis autoantibodies, antibodies accumulated inside myofibres in the same subcellular compartment as the autoantigen
- Biopsies from patients with autoantibodies targeting transcriptional regulators showed transcriptomic patterns consistent with autoantigen dysfunction
- Anti-PM/Scl (nuclear RNA exosome complex): accumulation of divergent transcripts and long non-coding RNAs, typically degraded by the exosome
- Patient antibodies introduced into cultured muscle cells recapitulated the transcriptomic effects seen in human disease
Further findings
- Supporting evidence suggested myositis autoantibodies recognising other autoantigens may also disrupt their targets' function
Original publication
Pathological autoantibody internalisation in myositis. Ann Rheum Dis. Published 21 October 2024. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →