PATIENTS with systemic sclerosis (SSc) who test positive for high levels of anti-muscarinic 3 receptor (anti-M3R) antibodies may face a more severe clinical course, particularly involving gastrointestinal (GI) complications, according to a new study.
In a cohort of 132 SSc patients enriched for GI symptoms, researchers found that 25% had high-titer anti-M3R antibodies. These patients were significantly more likely to have diffuse cutaneous disease, high GI symptom severity, and co-existing autoantibodies such as anti-RNPC3 and anti-U1RNP.
Notably, over 90% of high-titer patients had severe GI involvement, defined by a Medsger GI Severity Score of ≥2, compared to around 70% of those without high titers. While standard measures of GI motility and symptom burden (like whole-gut transit studies and UCLA GIT 2.0 scores) did not differ between groups, the presence of high-titer anti-M3R antibodies remained a strong predictor of severe disease in multivariable analyses.
These findings reinforce the potential of anti-M3R antibodies as a biomarker for identifying patients at risk of progressive GI dysfunction in systemic sclerosis. The association with additional autoantibodies and diffuse disease suggests a broader role for anti-M3R in shaping disease phenotype.
The authors suggest that testing for anti-M3R antibodies could enhance clinical risk stratification and help identify candidates for future GI-focused clinical trials in systemic sclerosis.
Aleksandra Zurowska, EMJ
Reference
Ayla A et al. Anti-muscarinic 3 antibodies associate with a severe clinical phenotype in patients with systemic sclerosis. Rheumatology. 2025;DOI: 10.1093/rheumatology/keaf197.
