Anti-muscarinic 3 antibodies associate with a severe clinical phenotype in patients with systemic sclerosis

Abstract

Objectives

Functional antibodies play a role in SSc gastrointestinal (GI) disease, but their clinical relevance is unclear. We examined GI and extraintestinal features associated with anti-M3R antibodies in SSc patients.

Methods

In a cohort enriched for GI symptoms, SSc patients were tested for anti-M3R antibodies using an enzyme-linked immunosorbent assay. High-titers were defined a priori based on the top quartile of anti-M3R titers to enhance specificity. Clinical features, including high GI severity (Medsger GI Severity Score of ≥ 2), whole-gut transit study data, and UCLA GIT 2.0 scores, were compared between patients with and without high-titer anti-M3R antibodies.

Results

In 132 patients, 52 (39.4%) tested positive for anti-M3R antibodies and 33 (25%) had high-titer anti-M3R antibodies. Compared with patients without high titers, high-titer patients were more likely to have diffuse disease (43.8% vs 22.9%, p = 0.023), high GI severity (90.9% vs 69.7%, p = 0.019), and anti-RNPC3 (18.2% vs 6.1%, p = 0.036) and anti-U1RNP antibodies (21.2 vs 2.0%, p = 0.001). Whole-gut transit studies and UCLA GIT 2.0 scores were not different between the groups. In multivariable logistic regression analysis, high GI severity (OR: 4.50 [95% CI 1.11, 18.18], p = 0.035) and anti-U1RNP antibodies (OR: 20.36 [3.16, 131.14], p = 0.002) remained associated with high-titer anti-M3R antibodies.

Conclusion

Anti-M3R antibodies are associated with a more severe GI phenotype and distinct extraintestinal and serological features in SSc patients. Utilizing these features may optimize risk stratification in clinical practice and identify those likely to have progressive GI disease for clinical trials.

systemic sclerosis, scleroderma, gastrointestinal disease, M3R, muscarinic, antibody

Accepted manuscripts

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