Early detection of Lyme disease has long been a problem for patients and doctors. A new study published in Microbiology Spectrum suggests that FDA-cleared single-step immunoblot (IB) tests developed by IGeneX may improve the early diagnosis of the infection, addressing a longstanding challenge in identifying cases during the initial stages when treatment is most effective.
The new single-step immunoblot tests detected antibodies in 58.3% of early-stage Lyme disease cases, compared with 30.0% using standard two-tier testing (STTT). This nearly doubles detection during the earliest phase of infection. The findings are based on an analysis of more than 1,100 serum samples, including well-characterized specimens from the Centers for Disease Control and Prevention (CDC) and the Bay Area Lyme Foundation’s Lyme Disease Biobank.
Unlike conventional STTT, which relies primarily on a single Borrelia burgdorferi strain and requires sequential testing, the new IgG and IgM immunoblot assays incorporate recombinant protein antigens from multiple species and strains found in the United States and Europe. According to the investigators, this broader antigen coverage enhances antibody detection while simplifying laboratory workflows by eliminating the need for multiple testing steps.
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These findings represent a meaningful advancement in Lyme disease diagnostics, particularly given that commonly used FDA-cleared MTTT and STTT testing methods have been shown to miss 64–78% of early Lyme disease cases. Jyotsna S Shah, PhD, lead author of the study and president of IGeneX, said in a statement.
Accuracy in Real-World Samples
The study also evaluated performance in 290 acute-phase samples from the Lyme Disease Biobank, where the IgG immunoblot significantly outperformed standard two-tier testing. When the IgG and IgM assays were used together, antibodies were detected in 30.2% of patients with confirmed erythema migrans lesions, compared with 20.6% using STTT. Investigators reported that discrepancy analysis confirmed 21 of 22 samples that were positive by the immunoblot but negative by STTT were true positives.
In addition to improved sensitivity, the assays demonstrated high specificity across 387 control samples representing conditions that can produce cross-reactive antibodies, including other tick-borne diseases, autoimmune disorders, viral infections, and pregnancy. Researchers observed only one IgM false-positive result, corresponding to approximately 99.7% specificity for IgM and 99.4% to 100% specificity for IgG. No cross-reactivity was observed with the IgG assay.
The improved diagnostic performance is attributed to several design features, including a proprietary Lyme Screen Antigen derived from immunodominant regions of the VlsE protein across multiple Borrelia species, along with additional antigens such as OspA and OspB that broaden immune response detection.
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It is difficult to overstate how often patients are told to “wait and see” when standard tests come back negative, despite strong clinical symptoms. This approach often leads to delayed treatment and chronic complications, a frustrating cycle that these new assays aim to break. By focusing on a wider array of antigens, the technology reduces the window of opportunity for the bacteria to hide from the immune system.
Streamlined Laboratory Workflow
There is an urgent need for more accurate diagnostic tests for Lyme patients, particularly in early-stage disease when standard testing falls short. Liz Horn, PhD, MBI, principal investigator of the Lyme Disease Biobank and study co-author, said in a statement. “This study demonstrates how a more sensitive, streamlined approach can improve detection and highlights the potential of this technology to support earlier and more accurate diagnosis for Lyme patients.”
The immunoblot assays evaluated in the study serve as the basis for the FDA 510(k)-cleared iDart IgG and IgM Immunoblot Tests, which are intended for the laboratory diagnosis of Lyme disease. Researchers noted that all samples in the study were tested in a blinded manner, with independent statistical validation and discrepancy analyses performed using clinical and serological criteria.