#5-02E. Unmasking Seronegative Sjögren’s: The Diagnostic Power of Muscarinic Autoantibodies (ARD, 2026)

Are we missing cases of Sjögren’s disease because we rely too heavily on traditional autoantibody panels? This study evaluated the presence and function of autoantibodies against muscarinic acetylcholine receptors (M1R to M5R) in patients with Sjögren’s disease (SjD). Researchers found a significant increase in these autoantibodies among SjD patients compared to healthy controls. Furthermore, functional analyses demonstrated that these IgG autoantibodies actively inhibit calcium signaling pathways mediated by M1R, M3R, and M5R12. The most compelling clinical finding is that a combination of anti-M2R, M3R, and M5R autoantibodies can successfully identify approximately 30% of Ro/SSA-negative SjD patients, offering a novel diagnostic avenue for historically seronegative cases. However, when critically appraising this study, it is important to note that the functional assays were conducted in an in vitro environment using engineered CHO cells, which may not fully replicate the complex physiological dynamics and signaling processes of primary human salivary gland tissues in vivo4. For clinicians, these findings are highly relevant as they introduce promising non-invasive biomarkers that could minimize the need for invasive biopsies in seronegative patients, while simultaneously laying the groundwork for personalized, targeted therapies aimed at preserving exocrine function.

Citation: Engelke F. Functional insights into autoantibodies targeting muscarinic acetylcholine receptors in Sjögren’s disease. Annals of the Rheumatic Diseases. 2026. DOI: 10.1016/j.ard.2026.06.016

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