Performance evaluation of a radioimmunoprecipitation assay for the detection of N-type voltage-gated calcium channel antibodies

• Published in: Journal of immunological methods 2021-09, Vol.496, p.113102-113102, Article 113102
• Main Authors: Lozier, Bucky K., Haven, Thomas R., Tebo, Anne E., Peterson, Lisa K.
• Format: Article
• Language: English
• Subjects: Autoantibodies; Autoimmunity; Lambert-Eaton Myasthenic Syndrome; Paraneoplastic syndrome; Voltage-gated calcium channel
• ISSN: 0022-1759; 1872-7905
• DOI: 10.1016/j.jim.2021.113102

In this study, we assessed the performance characteristics of a laboratory-developed radioimmunoassay (RIA) to detect N-type voltage-gated calcium channel (N-VGCC) antibodies found in several autoimmune neurologic diseases. Four hundred and forty-five (n = 445) sera were evaluated, including 156 sera (50 positive and 106 negative for N-VGCC antibodies) previously tested at Mayo Clinic Laboratories (MCL) and 289 controls (n = 187 disease and n = 102 healthy). Specimens were analyzed with the RIA using N-VGCC labeled with 125I-ω-conotoxin GVIA. The RIA was compared to the predicate MCL assay using a tiered positive predictive value (PPV) approach. Other performance characteristics evaluated included specificity, precision, interference, and stability. Qualitative inter-laboratory agreement based on tiered PPVs was 100% for results >1.00 nmol/L (71% PPV), 48% for results of 0.10–0.99 nmol/L (24% PPV) and 22% for results of 0.04–0.10 nmol/L (19% PPV). Negative results showed 90% agreement (n = 106). Specificity in controls positive for other neural autoantibodies and healthy controls were 87% and 100%, respectively. Acceptable results were observed for other performance characteristics. Inter-laboratory correlations demonstrate equivalence between assays with some discrepancies between low positive results. 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. •N-VGCC antibody test can contribute to the diagnosis of LEMS•Relevance of antibody in routine evaluation is limited by availability of testing•This study demonstrates comparable performance for two N-VGCC antibody assays•Discrepant low positive N-VGCC results were associated with autoimmunity but were not specific for LEMS•Efforts to harmonize assays for optimal patient categorization are needed