A Comparison of Lyme Serological Testing Platforms with a Panel of Clinically Characterized Samples from Various Stages of Lyme Disease

Abstract

Background: In 2019, the CDC updated serology testing guidelines for Lyme disease diagnosis to include alternative modified two-tiered testing that replaces the western blots of standard testing with an additional ELISA. Antibody-capture serological assays have also been used as an aid for Lyme diagnosis. A panel of clinically characterized samples from the CDC was tested to compare modified two-tiered testing to the standard two-tiered algorithm and an antibody capture immunoassay. Methods: A CDC panel of 92 samples comprised a range of samples including early Lyme, Lyme neuroborreliosis, Lyme arthritis, infections by other pathogens, and healthy controls. The panel was tested on a standard two-tiered platform by the CDC, the ZEUS Borrelia Test System for modified two-tiered testing, and a lab-developed antibody-capture serological assay. Sensitivity and specificity results from each assay were compared to determine significance. Results: The antibody-capture assay demonstrated increased sensitivity but decreased specificity compared to the modified and standard two-tiered platforms. There was no statistical difference found between the modified and standard two-tiered platforms. Conclusions: Improved sensitivity of antibody-capture when testing early Lyme disease samples is offset by decreased specificity, especially with syphilis-positive samples. Modified two-tiered testing is similar to standard two-tiered methods while also being more scalable and simpler to interpret.