Is the initial test for Lyme disease an antibody serology test?

From the Guidelines

Lyme antibody serology is the recommended initial test for diagnosing Lyme disease, using a two-tiered approach consisting of an enzyme-linked immunoassay or immunofluorescence assay, followed by reflexive immunoblotting, as outlined in current US guidelines. This approach is supported by the study published in Emerging Infectious Diseases in 2016 1, which highlights the importance of proper interpretation of laboratory tests in the context of symptoms and timing of illness. The sensitivity of the two-tiered testing is low (30%–40%) during early infection, but increases to 70%–100% for disseminated Lyme disease, with a high specificity (>95%) during all stages of the disease 1.

Key Points to Consider

• The two-tiered testing approach is necessary to confirm the diagnosis of Lyme disease, especially in patients without the characteristic erythema migrans rash.
• The initial screening test should be followed by a Western blot test to confirm the diagnosis, if the result is positive or equivocal.
• Antibodies may not be detectable in the first few weeks of infection, so patients with recent tick exposure and characteristic symptoms may be treated empirically without waiting for test results.
• Clinical correlation with symptoms and tick exposure history remains essential for optimal interpretation of test results.
• The test should be performed by a laboratory using validated methods to ensure accurate results.

Testing Approach

The testing approach for Lyme disease involves:

• Enzyme-linked immunoassay or immunofluorescence assay as the initial screening test
• Reflexive immunoblotting to confirm the diagnosis, if the initial test is positive or equivocal
• Consideration of clinical symptoms and tick exposure history in the interpretation of test results.

From the Research

Lyme Antibody Serology Initial Test

• The Centers for Disease Control and Prevention recommends a 2-tier serologic approach to Lyme disease laboratory diagnosis, which includes an initial serum enzyme immunoassay (EIA) for antibody to Borrelia burgdorferi, as stated in the study 2.
• The initial test is typically followed by supplementary IgG and IgM Western blotting of EIA-positive or -equivocal samples, but Western blot accuracy is limited by subjective interpretation of weakly positive bands, false-positive IgM immunoblots, and low sensitivity for detection of early disease 2.
• Alternative approaches, such as multiplex immunoassays, have been developed to improve test performance, particularly in early disease detection, as seen in the study 2, which found that a multiplex assay for VlsE1-IgG and pepC10-IgM antibodies performed as well as or better than Western blotting for Lyme disease diagnosis.
• Other studies have also explored the use of different antigens and testing methods to improve the sensitivity and specificity of Lyme disease diagnosis, such as the evaluation of in vivo expressed Borrelia burgdorferi antigens for improved IgM serodiagnosis of early Lyme disease 3.
• The importance of careful interpretation of serologic test results is emphasized, as positive Borrelia IgM antibodies in healthy individuals with nonspecific clinical symptoms are likely a false-positive result for Lyme disease, and serology as a single diagnostic tool has a very limited value 4.
• The use of enzyme-linked immunosorbent assays (ELISAs) with recombinant antigens has also been investigated, and has been found to be a useful tool for the serologic diagnosis of Lyme borreliosis, particularly when used in conjunction with Western blot analyses 5.