Ganglionic acetylcholine receptor autoantibodies in patients with autoimmune diseases including primary biliary cirrhosis

Abstract

Objectives: Autonomic dysfunction is closely associated with autoimmune diseases (AID) including primary biliary cirrhosis (PBC). The objective of this study was to determine the prevalence of anti-ganglionic (nicotinic) acetylcholine receptor (gAChR) antibodies in patients with AID.

Methods: We determined the presence of gAChR antibodies in serum samples from 146 patients (systemic lupus erythematosus [SLE] = 32; rheumatoid arthritis [RA] = 43; systemic sclerosis [SSc] = 38; PBC= 33) without information regarding autonomic symptoms, as well as 34 patients with other neurological diseases [OND], and 73 healthy controls [HC]. We specifically analyzed sera for anti-gAChRα3 and -β4 antibodies using the luciferase immunoprecipitation system (LIPS) assay.

Results: LIPS assay detected anti-gAChRα3 and -β4 antibodies in the sera from patients with SLE (12.5%, 4/32), RA (18.6%, 8/43), SSc (13.2%, 5/38), PBC (9.1%, 3/33), OND (2.9%, 1/34), and HC (0.0%, 1/73). There were no significant correlations between the levels of anti-gAChRα3 and -β4 antibodies, and the total titers of autoantibodies in AID.

Conclusions: The results demonstrated a significant prevalence of anti-gAChR antibodies in patients with AID, which is independent of the production of other autoantibodies in patients with autoimmune diseases. These anti-gAChR antibodies could mediate the autonomic dysfunction involved in the autoimmune mechanisms of AID.

Keywords:

• Anti-ganglionic acetylcholine receptor antibodies
• Primary biliary cirrhosis
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Systemic sclerosis

Acknowledgments

We are indebted to the members of the Nagasaki Kawatana Medical center department of neurology for discussing some issues for this study and to Nana Kusumoto for providing excellent secretarial support.

Conflict of interest

The authors declare no conflicts of interest. This work was supported by the Neuroimmunological Disease Research Committee and the Ministry of Health, Labor, and Welfare, Japan and the Ministry of Education, Culture, Sports, Science, and Technology of Japan [JSPS KAKENHI Grant Number 25461305].