Systemic sclerosis & Raynaud's
Antimitochondrial antibodies in systemic sclerosis target enteric neurons and are associated with gastrointestinal (GI) dysmotility
Authors' conclusion
AM2A in SSc patients are associated with slower GI transit. SSc autoantibodies penetrate live cells in vitro, and SSc-AM2A penetrates live cells to target the mitochondrial M2 antigen and cause functional deficits.
Study context
- Population
- Well-characterised patients with systemic sclerosis (SSc)147 analysed
- Participants
- 154 patients
- Exposure
- Antimitochondrial M2 autoantibodies (AM2A)-positive vs AM2A-negative SSc patients
- AM2A-positiven = 19
- Outcome
- Association of AM2A with GI dysmotility (GI transit)
Methodological detailsELISA screening, in vitro cell and tissue culture
- ELISA screening
- In vitro cell and tissue culture
Main finding
As reported in the abstract
GI transit, AM2A positivity
Β (oesophageal transit)
−14.4
95% CI −26.2 to −2.6
AM2A-positive
Β (gastric transit)
−7.9
95% CI −14.1 to −1.6
AM2A-positive
AM2A-positive
12.9%
19
Observational data: associations, not effects.
Further findings
Mechanistic findings
- TOM-20 and M2 enriched in human enteric nervous system (ENS) neurons, specifically mesoderm-derived enteric neurons (MENs)
- SSc autoantibodies penetrated live murine MENs and HepG2 cells in vitro; AM2A localised to mitochondria and bound M2 antigen
- SSc-AM2A penetration of HepG2 cells altered cellular respiration (Seahorse assays)
Original publication
Antimitochondrial antibodies in systemic sclerosis target enteric neurons and are associated with GI dysmotility. Ann Rheum Dis. Published 27 June 2025. doi:10.
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