From Pathogen to Infectious Disease Diagnosis: Multispecies Immunoblot Nearly Doubles Early Lyme Disease Detection

This is the latest episode of our From Pathogen to Infectious Disease Diagnosis podcast, where we discuss the relationship between clinicians and laboratory professionals and detail the latest in diagnostics.

Lyme disease diagnosis has traditionally relied on tests that have been shown to miss 64-78% of early Lyme disease cases.¹ If not treated promptly, Lyme disease may progress to a debilitating stage that may include paralysis, agonizing joint pain, neurological problems, severe headaches, memory, hearing, and vision problems, and inflammation of the brain and heart.

Joseph J. Burrascano Jr, MD, is a scientific advisor with IGeneX and the Bay Area Lyme Foundation and a founding member of the International Lyme and Associated Diseases Society (ILADS). He says clinicians often cannot rely on symptoms alone in early infection. The characteristic erythema migrans rash appears in fewer than half of cases and may be missed or mistaken for something else.

"Lyme disease, especially in the early stages, is just a clinical diagnosis because none of the symptoms really are very specific: aches and pains, headache, fatigue, maybe a fever," Burrascano said. "So if the rash is absent, it's really a lot of guesswork, and clinicians therefore have to rely on testing. But until now, early testing for Lyme disease has been terribly poor."

Study Data

In a recent peer-reviewed study, IGeneX's IgG immunoblot detected antibodies in 58.3% of CDC stage 1 Lyme disease samples, compared with 30.0% for standard two-tier testing.² Burrascano notes delayed diagnosis is one of the main drivers of persistent and chronic symptoms. A test with nearly double the sensitivity is therefore a welcome addition.

According to the study authors, the immunoblots use recombinant antigens from seven US and European Borrelia species and two US B burgdorferi strains, rather than a lysate of a single laboratory strain.² The tests also score antibodies to outer surface proteins A and B (OspA and OspB), which standard two-tier tests do not use. Specificity ranged from 99.4% to 100% for IgG and reached 100% for IgM in healthy controls. Across 387 sera from potentially cross-reactive conditions, including other tick-borne diseases and autoimmune disorders, the IgG test produced no false positives and the IgM test produced one.²

"The standard two-tier test is derived from a lysed organism, a single strain of a single species that came not from a human but from a tick, from an island off the coast of New York," Burrascano said. "Now we know the Lyme infection is very diverse. Borrelia is a very diverse organism, and what's in New York may be different from what's in Minnesota or California. So we have a test that's more sensitive, much more specific, and covers not one but a broad range of actual human infections."

The test is also self-contained. A broadly reactive Lyme Screen Antigen (LSA) and the full antigen panel run on the same strip, so a single order delivers a two-tiered result.² Burrascano adds the high specificity helps clinicians in both directions: it confirms true infections and rules out patients who tested positive on older assays but never had Lyme disease.

The study forms the basis for the FDA 510(k)-cleared iDart IgG and IgM Immunoblot tests.^2,3 The immunoblots are already available directly through the IGeneX laboratory. The company is converting them into kits outside laboratories, hospitals, and clinics can run in-house. Burrascano expects insurance billing codes for the kits by early next year. He notes the current laboratory tests are covered by traditional Medicare, with some commercial insurers reimbursing up to 80%.

On treatment, Burrascano cautioned against the single-dose doxycycline approach some clinicians use for early disease, saying it has never been proven to work. More experienced clinicians are instead starting patients on standard courses of doxycycline, amoxicillin, or cefuroxime.

References

1. Horn EJ, Menefee B, Schotthoefer AM, et al. Evaluation of standard and modified two-tiered testing algorithms using well-characterized early Lyme disease samples. J Clin Microbiol. 2026;64(5):e01187-25. doi:10.1128/jcm.01187-25

2. Shah JS, Liu S, Calalo-Ramos C, et al. Single-step immunoblot tests with recombinant protein antigens for detecting IgG and IgM antibodies in Lyme disease. Microbiol Spectr. 2026;14(8):e00199-26. doi:10.1128/spectrum.00199-26

3. New FDA-cleared single-step immunoblot IGeneX tests improve early detection of Lyme disease, study finds. News release. IGeneX; July 15, 2026. Accessed October 5, 2026. https://igenex.com/press-release/new-fda-cleared-single-step-immunoblot-igenex-tests-improve-early-detection-of-lyme-disease-study-finds

4. New single-step test nearly doubles early Lyme disease detection. Contagion. July 15, 2026. Accessed October 5, 2026. https://www.contagionlive.com/view/new-single-step-test-nearly-doubles-early-lyme-disease-detection