Ganglionic acetylcholine receptor autoantibody: oncological, neurological, and serological accompaniments

Abstract

Objective: To describe the clinical utility of the nicotinic ganglionic acetylcholine receptor (alpha3-AChR) autoantibody as a marker of neurological autoimmunity and cancer.

Design: Case-control study.

Setting: Mayo Clinic, Rochester, Minnesota.

Patients: A total of 15,000 patients seen at Mayo Clinic (2005-2007) and evaluated on a service basis for paraneoplastic neurological autoimmunity for whom clinical information was obtained retrospectively by medical record review as well as 457 neurologically asymptomatic patients or control subjects of whom 173 were healthy, 245 had lung cancer, and 39 had systemic lupus erythematosus or Sjögren syndrome.

Outcome measures: Neurological, oncological, and serological associations of alpha3-AChR autoantibody seropositivity.

Results: Of 15,000 patients tested on a service basis, 1% were seropositive (median, 0.12 nmol/L; range, 0.03-18.8 nmol/L; normal, < or =0.02 nmol/L), 55% were male, and the median age was 65 years. Cancer was found (new or by history) in 24 of 78 patients evaluated for cancer while at Mayo Clinic (30%); 43% had adenocarcinoma (more patients had breast cancer than prostate, lung, and gastrointestinal cancers; each of the latter groups had about the same number of patients). Of 12 patients with high antibody values (> or =1.00 nmol/L), 83% had pandysautonomia. Of 85 patients with medium antibody values (0.10-0.99 nmol/L), neurological presentations were more diverse and included peripheral neuropathies (36%), dysautonomia (20%, usually limited), and encephalopathy (13%). Of 58 patients with low antibody values (0.03-0.09 nmol/L), 54% had a nonautoimmune neurological disorder or no neurological disorder. Of 245 control patients with lung cancer, 7.8% were seropositive. Only 1 of 212 control patients without cancer (0.5%) was seropositive (P < .001).

Conclusion: The detection of alpha3-AChR autoantibody aids the diagnosis of neurological autoimmunity and cancer.

Figure 1

Nicotinic ganglionic acetylcholine receptor antibody (α3-AChR Ab) values detected in 155 patients with neurological disease (those referred for paraneoplastic evaluation) and 457 controls (those with cancer only or those without neurological disease or cancer). SLE indicates systemic lupus erythematosus; circles, patients referred for paraneoplastic evaluation; triangles, cancer only; and diamonds, controls without neurological disease or cancer.

Figure 2

Positron emission tomographic (PET) images of a man presenting at 70 years of age with encephalopathy; nicotinic ganglionic acetylcholine receptor antibody (α3-AChR Ab) value, 0.10 nmol/L. Results of initial evaluation for cancer including computed tomography were normal. A subsequent PET scan revealed a hypermetabolic focus in the superior right lobe of the thyroid gland (arrow). Ultrasound-guided fine-needle aspiration revealed papillary carcinoma.