Muscarinic-3 acetylcholine receptor autoantibody in patients with systemic sclerosis: contribution to severe gastrointestinal tract dysmotility

Objective: Patients with systemic sclerosis (SSc) complicated by severe gastrointestinal tract (GIT) dysmotility at an early stage are difficult to treat and mortality is high. To clarify the pathogenesis of GIT involvement, the occurrence of autoantibody was investigated for muscarinic-3 acetylcholine receptor (M3R) in patients with SSc. Methods: Fourteen patients with severe GIT involvement ( malabsorption syndrome and/or pseudo-obstruction) within 2 years of SSc onset ( group 1) were enrolled in the present study. Sixty-two patients with SSc without severe GIT involvement within 2 years of onset ( group 2) were also recruited, along with 70 healthy control subjects. Using an established enzyme immunoassay (EIA) system detecting autoantibody against the second loop domain of M3R, the presence of an anti-M3R antibody was examined in SSc patients. Results: The mean optical density ( OD) titres of group 1 were significantly higher than those of group 2 (0.65 ( SD 0.58) vs 0.066 (SD 0.13), p<0.001). The positivity of anti-M3R antibody was significantly higher in group 1 than in group 2 (9/14 vs 3/62, p = 2.5 x 10(-6) by Fisher's exact test). The cutoff OD was calculated from the EIA reaction of the 70 healthy controls ( the mean value plus 2 SD was 0.295). Conclusion: The findings indicated that anti-M3R antibody very frequently appears in patients with SSc, which is accompanied by severe GIT involvement, suggesting that M3R-mediated enteric cholinergic neurotransmission may provide a pathogenic mechanism for GIT dysmotility in SSc.