Spatial transcriptomics reveals mechanism of autoimmunity driven by internalised autoantibodies
Authors' conclusion
Together, these findings establish autoantibody internalisation as a mechanism of tissue injury in autoimmunity, suggesting its broader relevance across autoantibody-mediated diseases.
Study context
- Population
- Muscle biopsies from patients with autoimmune diseases and healthy controls; anti-Mi2 DM and anti-PM/Scl scleromyositis as model diseases
- Participants
- 814 muscle biopsies
Methodological detailsbulk RNA sequencing, external validation cohort, IgG electroporation in vitro, immunofluorescence, spatial transcriptomics
- Bulk RNA sequencing
- External validation cohort
- IgG electroporation in vitro
- Immunofluorescence
- Spatial transcriptomics
Main finding
As reported in the abstract
- Reproducible, autoantibody-specific transcriptomic signatures consistent with autoantigen dysfunction across cohorts
- Electroporation of purified patient IgG into healthy primary cells recapitulates disease-associated transcriptional programmes
- Signatures linked to cellular injury and distinct inflammatory responses: type I IFN and TGFβ signalling in anti-Mi2 DM; type II IFN signalling in anti-PM/Scl scleromyositis
- Programmes observed in muscle fibres and also in macrophages, endothelial cells and fibroblasts/fibroadipogenic progenitors
- Transfer of immunoglobulin (Ig) RNA from antibody-secreting cells to adjacent target cells expressing disease-specific programmes
- Antibody internalisation also observed in skin (anti-Mi2, anti-PM/Scl) and in tissues from anti-U1RNP MCTD, anti-Ku overlap syndrome and anti-Scl70 SSc
Original publication
Spatial transcriptomics reveals mechanism of autoimmunity driven by internalised autoantibodies. Ann Rheum Dis. Published 23 July 2026. doi:10.
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