Introduction:
Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common tick-borne illness in the United States and Europe. It is primarily transmitted through the bite of infected black-legged ticks (Ixodes scapularis and Ixodes pacificus). Early detection and treatment are crucial for preventing the disease from progressing to more severe stages. When Lyme disease is suspected based on clinical signs and symptoms, serologic testing plays a key role in confirming the diagnosis. This blog will focus on the two-step testing process for Lyme disease: ELISA (enzyme-linked immunosorbent assay) followed by Western blot.
Why Serologic Testing is Important
Lyme disease presents with a variety of symptoms, ranging from the characteristic “bull’s-eye” rash (erythema migrans) to flu-like symptoms, joint pain, and neurological complications. In many cases, the rash may be absent or unnoticed, and the symptoms can mimic other conditions, making diagnosis challenging. This is where serologic testing becomes valuable.
However, it’s essential to note that serologic tests detect antibodies produced by the immune system in response to infection, not the bacteria itself. As a result, the timing of testing is crucial—antibodies may not be detectable in the very early stages of the disease.
Step 1: ELISA for Lyme Disease
The first step in diagnosing Lyme disease serologically is the enzyme-linked immunosorbent assay (ELISA). This test measures the presence of IgM and IgG antibodies against Borrelia burgdorferi.
- IgM antibodies: These are the first antibodies produced by the immune system in response to infection and are typically detectable 1-2 weeks after exposure. They are most relevant in the early stages of Lyme disease.
- IgG antibodies: These antibodies appear later, usually 4-6 weeks after infection, and persist for months to years. IgG testing is more relevant for detecting later stages of the disease.
How ELISA Works:
- The ELISA test is a sensitive screening test that detects antibodies in the blood by attaching the patient’s antibodies to antigens coated on a plate. An enzyme-labeled antibody specific to human IgM or IgG is added, and if the patient’s antibodies are present, they will bind, leading to a color change that indicates a positive result.
Limitations of ELISA:
- False negatives: If the test is done too early (within the first few days of infection), the immune response may not have produced enough antibodies, leading to a false negative result.
- False positives: ELISA can occasionally produce false positive results due to cross-reactivity with other infections or autoimmune conditions.
Because of these limitations, a positive or equivocal ELISA result must be confirmed by a more specific test—the Western blot.
Step 2: Western Blot Confirmation
After a positive or equivocal ELISA result, the Western blot is used as a confirmatory test. This test is more specific and detects antibodies to several distinct antigens of Borrelia burgdorferi, helping to confirm the diagnosis.
- IgM Western blot: This is used for confirming early Lyme disease and requires the presence of at least 2 out of 3 specific bands (proteins) to be considered positive.
- IgG Western blot: Used for later stages of Lyme disease, a positive result requires the presence of at least 5 out of 10 specific bands.
How Western Blot Works:
- The Western blot separates Borrelia proteins by size using gel electrophoresis. The patient’s antibodies are then applied to the separated proteins, and if antibodies specific to Lyme disease are present, they will bind to certain bands corresponding to Borrelia proteins. These bands are then visualized to confirm the presence of the infection.
Why the Two-Step Process is Important:
- The two-step testing approach helps improve both the sensitivity and specificity of Lyme disease diagnosis. ELISA alone is not sufficient due to its potential for false positives, while the Western blot adds specificity by confirming the presence of antibodies to multiple Borrelia proteins.
When Should Lyme Serology Be Performed?
Serologic testing is not recommended in all cases. The decision to perform Lyme serology should be based on the patient’s clinical presentation and risk factors for exposure (e.g., known tick bite, residence in an endemic area).
- Early Lyme disease: If a patient presents with the characteristic erythema migrans rash and a history of tick exposure, serologic testing is often unnecessary, and empirical treatment with antibiotics can be initiated.
- Disseminated or late Lyme disease: Serologic testing becomes more useful when patients present with nonspecific symptoms (e.g., arthritis, neurological symptoms) without a clear rash or tick bite history. Testing is particularly important for patients with late manifestations, such as Lyme arthritis or neuroborreliosis.
Interpreting Lyme Serology Results
- Positive ELISA and Positive Western Blot: This indicates a high likelihood of active or recent Lyme disease. Treatment should be initiated based on the stage of the disease and clinical symptoms.
- Positive ELISA and Negative Western Blot: This likely represents a false positive ELISA, especially if the patient has no significant clinical symptoms of Lyme disease. In this case, further evaluation or testing may be necessary.
- Negative ELISA: A negative result likely rules out Lyme disease, particularly if performed more than a few weeks after symptom onset. However, if the test is done too early (within the first week), it may need to be repeated if symptoms persist or progress.
Treatment Following Diagnosis
Once Lyme disease is confirmed through serologic testing, treatment is typically initiated based on the stage and severity of the disease. Antibiotics are the cornerstone of treatment, with options including:
- Doxycycline (for early or mild disease)
- Amoxicillin or cefuroxime (for patients who cannot take doxycycline)
- Ceftriaxone or penicillin G (for more severe or late-stage disease, such as neuroborreliosis)
Early and appropriate treatment usually results in a complete recovery, though some patients may experience lingering symptoms, often referred to as post-treatment Lyme disease syndrome (PTLDS).
Conclusion
The two-step process of Lyme serology testing—starting with ELISA and confirming with Western blot—is a reliable method for diagnosing Lyme disease in patients with non-specific symptoms or those in later stages of the disease. Understanding the nuances of these tests, including their timing and limitations, is crucial for accurate diagnosis and treatment. If you suspect Lyme disease, speak with your healthcare provider about testing and appropriate management based on your symptoms and risk factors.
