To assess the performance characteristics of a radioimmunoassay (RIA) to detect ganglionic acetylcholine receptor (gAChR) autoantibodies.

gAChR autoantibodies have been detected in a variety of clinical conditions such as autoimmune autonomic ganglionopathy, stiff person syndrome, as well as several rheumatic diseases including systemic sclerosis and coexist with striated muscle, neuromuscular AChR and VGKC antibodies. gAChR antibodies are detected in approximately 2% of patient sera evaluated for paraneoplastic antibodies; however, testing for this analyte is offered by few laboratories in the United States. Limited data exists on the performance characteristics including correlations between methods for detection of gAChR antibodies.

Two hundred seventy-four (n=274) sera were evaluated. These included sera from 163 patients (74 positive and 89 negative for anti-gAChR antibodies) previously tested at Mayo Clinic Laboratories (MCL) and 111 controls (n=36 ARUP disease controls and n=75 “self-reported” healthy individuals). All samples were tested by RIA using recombinant gAChR complexed with ¹²⁵I-labeled epibatidine. Performance was evaluated based on ranges established during validation testing (<8.5 pmol/L=negative, 8.5–11.6 pmol/L=indeterminate, >11.6 pmol/L=positive). Performance of the gAChR RIA was compared to results previously obtained for 163 serum samples tested at MCL based on the tiered positive predictive value (PPV) of the predicate assay. Assay specificity was assessed using controls.

Qualitative inter-laboratory result comparison based on the  tiered PPV of the predicate assay (MCL) demonstrated 76% agreement for results of 0.10–0.99 nmol/L (50% PPV; n=25) and 27% agreement for results of 0.03-0.10 nmol/L (46% PPV; n=49). Negative results showed 94% agreement (n=89). Clinical specificity was 92% (n=75) and diagnostic specificity was 92% (n=75).

Overall inter-laboratory correlation demonstrates equivalence; however, discrepancies were noted at levels close to the reference intervals for each assay. Collaborative efforts aimed at assessing the clinical spectrum associated with these antibodies and consensus for harmonizing test performance are required for optimal categorization of patients.