Muscarinic 3 receptor antibodies in Sjögren's disease: Evaluating assay variability and detection methods

The most common manifestations characterizing Sjögren's disease (SjD) are extensive ocular and oral dryness due to decreased lacrimal (keratoconjunctivitis sicca) and salivary gland function (xerostomia). Another hallmark of SjD is the presence of autoantibodies. Acinar cells in the exocrine glands express muscarinic-type-3-receptors (M3R), which act as regulators of saliva secretion. Studies have linked M3R-targeting autoantibodies to reduced saliva secretion in SjD. Earlier studies have proposed that anti-M3R antibodies can pose as potential SjD clinical markers and indicators of dryness. Although functional assays confirm that anti-M3R antibodies have inhibitory activity, other assays have shown a wide range of detection sensitivities for these antibodies (0-100%). Differences in assay type, reagents, or peptide conformation likely explain the wide variation in assay sensitivity and specificity. We searched PubMed/PubMed Central (up to 2024) to assess possible reasons for this discrepancy and identify the best assay with which to screen for these antibodies. This review highlights the importance of conformational assays and recommends standardization to improve diagnostic accuracy.