OBJECTIVES: G protein-coupled receptors (GPCRs) participate in various pathophysiological processes in Sjogren's disease (SjD); in particular, autoantibodies against muscarinic acetylcholine receptor 3 (M(3)R) inhibit the secretion of saliva and tears by exocrine glands. We aimed to identify autoantibodies targeting other muscarinic receptors in SjD and assess their potential functional relevance to signalling pathways. METHODS: Autoantibodies against all muscarinic acetylcholine receptor subtypes were investigated in the serum of patients with SjD (n = 347) using enzyme-linked immunosorbent assays (ELISAs). Healthy controls (HCs; n = 50), patients with non-Sjogren's sicca syndrome (NSS; n = 44), and patients with other autoimmune diseases (AIDs; n = 67) served as controls. To analyse the functional role of muscarinic receptor autoantibodies against muscarinic acetylcholine receptors 1 to 3 and 5 (M(1)R, M(2)R, M(3)R, and M(5)R, respectively), purified immunoglobulin (Ig) G fractions from patients with SjD (n = 10) and HCs (n = 10) were examined in Chinese hamster ovary (CHO) cells transfected with the specific receptor using calcium mobilisation and cyclic adenosine monophosphate (cAMP) accumulation assays. RESULTS: IgG autoantibodies against M(1)R to M(5)R were significantly increased in patients with SjD compared with HCs (p
