Lyme Disease Blood Tests: Everything You Need to Know

Lyme disease is a condition that often confuses not only patients but also doctors. Many expect blood tests to clearly confirm or rule out an infection – the reality is more complex. What blood tests for Lyme disease are available and how should they be properly interpreted? Why do results sometimes not match the symptoms? We provide detailed answers to these questions in the text below.

If you are looking for practical guidance on Lyme disease testing (which test to take, when, and how to proceed), you can find at the end of this article.

1. What Lyme Disease Tests Are Available and What Do They Detect?
2. How to Interpret Lyme Disease Blood Test Results:
▸ ELISA Test
▸ Western Blot Test
▸ EliSpot Test
3. When Should You Get Tested for Lyme Disease?
4. Where Can You Get Tested for Lyme Disease?
5. Testing for Lyme Disease Co-Infections
6. Our Recommendations for Lyme Disease Testing

What Lyme Disease Tests Are Available and What Do They Detect?

1. Basic Antibody Tests

The most commonly used blood tests for suspected Lyme disease are ELISA and Western Blot. Neither of these tests detects the Borrelia bacteria directly in the blood, but rather the presence of antibodies produced against these bacteria.

ELISA

ELISA is a quick test that detects whether IgM antibodies (typical of the acute phase of infection, but often present in chronic infections as well) or IgG antibodies (usually appearing in later or past stages) against Borrelia bacteria are present in the blood. ELISA results are straightforward to interpret – IgM and IgG can be positive or negative. This test is not very reliable, as it often shows false positives and false negatives.

Modern ELISA variants:

CLIA: A more modern and sensitive alternative to the standard ELISA test.
Tickplex: Based on the ELISA principle, capable of detecting persistent forms of Borrelia – those that survive in the body long-term despite treatment.

WESTERN BLOT

Western Blot is a more precise test that detects IgM and IgG antibodies that the immune system has produced against specific parts of the Borrelia bacteria. The immune system does not produce a single universal antibody against the entire bacterium; instead, it produces specific antibodies targeting various bacterial components recognized as foreign. For example, one type of antibody may target the bacterium's flagella used for movement, while another targets its outer membrane. Interpretation is therefore more complex but more accurate than ELISA.

Modern Western Blot variants:

ImmunoBlot (LineBlot): A newer and more precise alternative to Western Blot, which has replaced it in many countries.
SeraSpot®: A more accurate and standardized alternative to Western Blot.

2. Specialized T-Cell LTT Test:

ELISPOT

A modern test that measures whether and how many of a patient's T-cells produce the cytokine interferon-gamma (IFN-γ) upon contact with Borrelia, indicating their activity against the bacteria. Unlike antibodies, which typically start to form 4–6 weeks post-infection, T-cells respond earlier – approximately 2 weeks after infection ⁽¹⁾. In chronic stages, antibody levels may significantly decrease or disappear entirely, while the T-cell response often persists ⁽²⁾.

Modern EliSpot variant:

iSpot: In addition to IFN-γ, this test increasingly measures the cytokine interleukin-2 (IL-2). While IFN-γ is a marker of acute or active infection, IL-2 relates to immune memory and indicates convalescence or past infection. IL-2 values are sometimes included directly in the EliSpot test, which may also be listed under the name iSpot. A test analyzing both IFN-γ and IL-2 provides a more comprehensive view of cellular immune response and helps distinguish between ongoing, latent, or past infection ⁽⁴⁾.

3. Supportive Immune Test:

CD57+

As a supportive marker in chronic Lyme disease, the immune marker CD57+ is used to indicate the number of natural killer (NK) cells. These cells play a key role in defending the body against infections. It is important to emphasize that CD57+ is not a diagnostic test for Lyme disease. It is an immunological parameter that can indirectly reflect immune system weakening due to long-term infection, such as chronic Lyme disease.

Chronic Lyme infections can suppress immune system function over time, often resulting in lower CD57+ NK cell counts. Patients with chronic Lyme disease often have levels of 100/μl or lower. Low CD57+ levels are more common in patients with chronic neurological Lyme disease (neuroborreliosis) than in those whose symptoms are primarily muscular or joint-related. Studies also show that patients who respond to treatment with improvement experience a rise in CD57+ cells ⁽²⁾. However, this parameter is not part of standard diagnostics and is mainly used in specialized Lyme centers.

Interpreting Blood Test Results for Lyme Disease

Interpreting blood tests for Lyme disease is one of the most common sources of confusion between patients and doctors. Many expect a clear answer – either “yes” or “no” – but in reality, it’s a complex process that requires considering multiple factors, including the patient’s clinical picture and medical history.

ELISA Test Interpretation

A positive ELISA result indicates the presence of antibodies against Borrelia bacteria in the blood, which may reflect an ongoing or past infection. However, a positive result is always followed by a more detailed Western Blot test to confirm or rule out the diagnosis. ELISA can be positive even if the infection is not present. This may occur due to residual antibodies from a resolved infection or false positives caused by cross-reactivity with other conditions, such as Epstein-Barr virus (EBV) infection or autoimmune diseases.

Tip:

If you have no symptoms, no history of a tick bite, no red erythema migrans rash, and no discomfort despite a positive test result, treatment is usually not required.

Still, it’s wise to remain vigilant – if unexplained health problems arise later, such as fatigue, pain, neurological symptoms, sleep disturbances, mood swings, or cognitive issues, Lyme disease should be considered as a possible cause. In some cases, this may indicate reactivation of infection or a persistent, insufficiently treated infection ⁽⁷⁾.

In chronic Lyme disease, it is also common for patients to have long-term IgM antibodies in their blood, which are typically associated with the acute phase, while IgG antibodies, which appear in later stages, may be absent. This occurs because Borrelia bacteria can repeatedly change and adapt during their life cycle, for example by altering surface structures. In this way, they evade the immune system. Each such “transformation” and subsequent bacterial replication triggers the immune system as if it were a new infection, reactivating IgM production. The test result may therefore incorrectly indicate an acute phase even in chronic disease ⁽⁶⁾. Interestingly, the more severe the symptoms a patient reports, the less likely they are to have positive IgG antibodies ⁽³⁾.

A negative ELISA result indicates absence of antibodies, but this does not rule out Lyme disease. Antibodies usually develop 4–6 weeks post-infection, so the test may be negative if done too early. It may also be negative in late-stage disease due to immune suppression caused by the infection itself.

Dr. Donta’s research found that 52% of chronic Lyme patients had negative ELISA results but positive Western Blot results ⁽⁵⁾. Nevertheless, in practice, a negative ELISA often leads to automatic exclusion of Lyme diagnosis, even in patients with active infection, causing delayed treatment and unnecessary investigation of other causes.

Note: Today, the modern CLIA method is often used instead of ELISA, with visually identical results and interpretation.

Western Blot Test Interpretation

Western Blot interpretation is more complex. The result provides a list of bacterial components of Borrelia (= various antigens) against which antibodies were tested. Antigens in Lyme Western Blot are classified into three groups based on how clearly their presence indicates infection:

Highly specific antigens: Found only in Borrelia bacteria; antibodies against them do not occur in other infections. Their presence is strong evidence of Lyme disease.
Specific antigens: “Medium category” – mostly found in Borrelia, but may partially resemble antigens of other microbes. Antibodies against them increase diagnostic probability, especially when detected with highly specific antigens or typical symptoms.
Non-specific antigens: Present in other bacteria; antibodies may arise from other diseases and serve only as supplementary evidence for a positive result.

Sources: (10), (11), (12)

For interpretation, it’s ideal to look not only at the final positive/negative result but also at individual antigens. The selection of antigens can vary between labs. Ideally, results include actual antibody values for each antigen, not just positive/negative assessment. Standard labs usually don’t provide this – a specialized lab or request is needed. Western Blot criteria also differ – some labs require more positive antigens for a positive result, others fewer. A lab may report a negative result, but considering history and symptoms, it could still indicate active infection. In practice, patients with severe symptoms may have very low or no antibodies, while those with mild symptoms may have high antibodies. Lyme experts often consider the presence of even one highly specific antibody group combined with symptoms or tick exposure as proof of Lyme disease ⁽⁹⁾.

Despite higher accuracy, Western Blot may miss active infection in some cases due to weakened patient immune response, bacteria hiding in tissues, or antibodies bound in immune complexes that the test cannot detect ⁽⁹⁾. These scenarios are common in chronic Lyme disease.

It’s also important to note that a positive Western Blot does not automatically indicate active Borrelia bacteria – immune responses and antibodies can persist long after successful treatment. Therefore, Western Blot results should always be interpreted in the context of the patient’s overall clinical picture.

Tip: If you experience typical Lyme symptoms but Western Blot is negative, it is recommended to perform an EliSpot test, which evaluates the cellular immune response that ELISA and Western Blot do not detect.

ELISPOT (LTT) Test Interpretation

EliSpot results are expressed as stimulation index (SI):

up to 1 SI - negative result
2–3 SI - borderline (weakly positive) result
above 3 SI - clearly positive reaction

Three antigens are usually assessed:

Full Antigen – captures the response to the entire Borrelia burgdorferi antigen profile
Peptide Mix (OSP-Mix) – contains surface proteins (OspA, OspC, DbpA) from multiple Borrelia species for a broader immune response overview
LFA-1 – an antigen shared by Borrelia and human cells; a positive response may indicate an autoimmune process (e.g., lupus, rheumatoid arthritis)

It is important to note that SI level does not directly reflect disease severity, but only the intensity of the immune response to a specific antigen. A high SI does not mean a more severe course, and a low or negative result does not exclude infection, especially in late stages, weakened immunity, or when bacteria are hidden in tissues inaccessible to immune cells ⁽¹⁾.

Some experts also consider EliSpot useful for monitoring treatment efficacy – after successful therapy, the test should be negative approximately 4–8 weeks post-treatment ⁽²⁾. Nevertheless, results must be interpreted carefully as they can be influenced by immune status or the presence of other infections with similar antigens, which may lead to false-positive findings.

When Should You Get Tested for Lyme Disease?

Testing for Lyme disease is most meaningful when symptoms appear or there is a reasonable suspicion of infection. Typical situations include:

Appearance of a red rash erythema migrans after a tick bite (absent in up to two-thirds of patients ⁽¹³⁾),
Flu-like symptoms following a tick bite,
Persistent unexplained health issues with fluctuating intensity.

The range of problems chronic Lyme disease can cause is extremely wide. Symptoms may be physical or psychological – from fatigue, joint and muscle pain, tingling in the limbs, sleep or digestive disturbances, to memory issues, depressive states, or worsened condition after alcohol consumption.

To choose the correct Lyme disease test based on the stage of infection and to interpret it accurately, it is important to understand how the immune system responds after infection:

About 2 weeks after infection – T-cells activate and produce the cytokine IFN-γ; this early cellular signal is detected by EliSpot,
About 4–6 weeks after infection – IgM antibodies appear, which are measured by ELISA and Western Blot tests,
Later – IgM usually declines while IgG antibodies persist; however, in chronic forms of infection, IgG may be absent,
In chronic forms – antibodies are often no longer detectable, but the T-cell response, which EliSpot can reveal, remains.

Based on this, it is recommended to prioritize T-cell testing (EliSpot) in the early stages, use Western Blot for established but not yet chronic infections with intact immunity, and combine both tests for chronic forms to get a complete picture of the immune response. Keep in mind that test results may be influenced by the patient’s immune status, and paradoxical rises in antibody levels can even occur during treatment, signaling immune recovery. Therefore, test results should always be interpreted together with symptoms and medical history, as a single test can never definitively confirm or rule out Lyme disease ⁽³⁾.

Where Can You Get Tested for Lyme Disease?

There are 3 main ways to get tested for Lyme disease:

Through the standard healthcare system
As a self-payer at private laboratories
With a doctor specializing in Lyme disease (LLMD)

1. Through the standard healthcare system:

A general practitioner or a specialist (most often an infectious disease doctor, neurologist, or cardiologist) will usually start with a basic ELISA test. The more accurate Western Blot is only performed if the ELISA comes back positive. The fact that a weakened immune response in chronic cases can lead to false negatives, even when the infection is still present, is often overlooked. As a result, many patients with classic symptoms leave with a negative Lyme test. More advanced tests, such as EliSpot, iSpot, or CD57+, are generally not used in the standard system. The advantage, however, is that testing through the public healthcare system is covered by health insurance.

2. As a self-payer at private laboratories:

Basic ELISA and Western Blot tests are available on a self-pay basis at most private laboratories. Tests like EliSpot and CD57+ are generally not available at standard labs.

However, beyond ordinary labs, there are specialized laboratories focusing on tick-borne diseases. One of the best-known in Europe is the German lab ArminLabs, which offers a full range of modern tests – from standard ELISA and advanced SeraSpot® to Tickplex for persistent forms of Borrelia, as well as Western Blot (ImmunoBlot), EliSpot, iSpot, and CD57+.

ArminLabs.com
- ELISA: 47 €
- SeraSpot®: 108 €
- ImmunoBlot (modern version of Western Blot): 108 €
- Tickplex: 94 €
- EliSpot: 142 €
- iSpot: 218 €
- Immune cells CD3-/CD57+/CD56+/CD45+: 99 €*

* Prices are current as of September 2025 and may vary depending on the country from which the sample is sent. Shipping costs are additional.

You can order tests internationally: the lab will send a testing kit to your home. After collecting your blood sample, you return it with the completed form and requested tests via express shipping, and you can receive results within just a few days. This method is convenient and comprehensive, but the patient covers the full cost.

Other European labs offering specialized Lyme tests include Nordic Laboratories (Denmark), Biovis Diagnostics (Germany), or IMD Berlin (Germany).

In the USA and Canada, specialized Lyme tests are available through private labs such as IGeneX, Vibrant Wellness, Infectolab Americas, and DNA Connections.

Note: The information above is based on our experience and the experiences of Lyme disease patients, aimed at helping you navigate testing options. We have no partnerships or agreements with the laboratories mentioned.

3. With a doctor specializing in Lyme disease (LLMD):

If you prefer testing under the supervision of a specialist in Lyme disease and its co-infections, some countries have so-called LLMDs – doctors who focus specifically on Lyme disease and work directly with laboratories offering the most appropriate tests. Testing through an LLMD is not covered by health insurance, and the system varies from country to country.

Do you know of other testing options, or do you have personal experiences or up-to-date information that could be helpful to others? We’d be glad if you shared your insights at info@onlyx.com.

Testing for Lyme Disease Co-Infections

When someone is infected with Lyme disease, it’s almost always accompanied by other pathogens such as Bartonella, Babesia, Anaplasma, and others. Additionally, the weakened immune system in Lyme patients often triggers opportunistic infections, like Candida yeast or herpes viruses (HSV, EBV, CMV), which a healthy body can normally keep under control. These co-infections can significantly worsen overall health, making it sometimes necessary to treat them alongside Lyme disease.

A patient’s symptoms can often hint at the type of co-infection present. Characteristic symptoms of the most common co-infections include:

Bartonella: rash resembling stretch marks, sudden outbursts of anger (irritability or aggression), swollen lymph nodes, unexplained cough, shin pain, foot pain.
Babesia: chest and rib pain, intense night sweats (soaking pajamas or bedding), fluctuating body temperature, shortness of breath (feeling of not getting enough air).
Mycoplasma: respiratory infections, sinus inflammation or chronic congestion.
EBV Reactivation: extreme fatigue, mild sore throat, low-grade fever, flu-like feelings.

Testing for co-infections can be very useful, though it is often more costly. It is especially recommended for patients who do not experience expected improvement after prolonged Lyme treatment. In some cases, a co-infection may be the primary cause of symptoms rather than Lyme disease itself, and treating it can be crucial. In chronic cases, we recommend testing for co-infections using EliSpot through specialized laboratories such as ArminLabs or via doctors who specialize in Lyme disease. From our experience, the co-infections that tend to cause the most problems are Babesia and Bartonella.

Our Recommendations for Lyme Disease Testing

Based on our experience, we recommend the following approach if Lyme disease is suspected:

Acute Infection

After a tick bite, we recommend taking an EliSpot test two weeks after the bite. If the EliSpot test is not available or you prefer testing through the standard healthcare system, we recommend a Western Blot test (ideally 4–6 weeks after the bite). Interpret the results according to the instructions provided. If the test is positive, we recommend starting a 6-week course of antibiotics immediately, followed by herbal treatment for an additional three months after all symptoms have subsided.

Chronic Infection

Due to the low reliability of the ELISA test, we recommend going straight to a Western Blot test (ideally with a breakdown of values for each antigen).
If the Western Blot is negative, we recommend taking an EliSpot or iSpot test. For long-term issues, it may also be useful to include the CD57+ parameter.
All test results should be interpreted in combination with symptoms and patient history. A person without symptoms whose immune system can control the infection may test strongly positive. Conversely, a severely ill patient may test only weakly positive or negative. Always treat the patient, not the test result. If Lyme disease is confirmed and the patient has symptoms, treatment should start as soon as possible.
If all tests are negative, other diagnoses are excluded, but symptoms and history still suggest Lyme disease, we recommend considering trial treatment with antibiotics (under medical supervision) or an herbal protocol and observing the body’s response. Trial treatment can serve as a form of diagnostic confirmation. If a Herxheimer reaction occurs (temporary worsening of existing symptoms, flu-like state, fever), it is likely Lyme disease and reflects mass bacterial die-off. This reaction may not occur in everyone, as detox capacity and bacterial load are individual. Another indicator can be how you feel over time and whether symptoms improve. Trial treatment is also an option for patients with high suspicion of infection who cannot afford extensive testing.
If Lyme disease is confirmed but long-term treatment does not bring improvement, we recommend testing for co-infections.

Currently, there is no test that can confirm or rule out Lyme disease with 100% certainty. Therefore, it is equally important to evaluate symptoms, medical history, and the patient’s overall clinical picture. Laboratory tests are only one tool in the diagnostic process and should never be the sole criterion for treatment decisions.

Ing. Zuzana Klimentová

Author of the article

Zuzana is the heart and soul of Onlyx. She stands as living proof that recovery from chronic Lyme disease and a return to a full, vibrant life is not just possible but entirely within reach. After years of pain, uncertainty, and relentless searching for answers, she now enjoys full health, living a life free from limitations. With a deep passion for herbal medicine, holistic health, and the profound connection between the mind and body, Zuzana is dedicated to understanding the root causes of illness rather than just treating symptoms. Her approach is marked by a sharp attention to detail and a genuine desire to help those who are currently on their own journey to healing. For Zuzana, natural healing is not just a profession—it is her true purpose. She is committed to showing that even the most challenging and seemingly hopeless situations can be the starting point for something much greater.