Lyme Antibody (IgG)

Lyme disease, caused by the spirochete bacterium Borrelia burgdorferi (and related species in Europe), is the most common tick-borne illness in North America and Europe. Diagnosis relies heavily on antibody testing because the bacteria are difficult to culture and are present in blood only transiently. Understanding the antibody response — particularly the difference between IgG and IgM — is crucial for interpreting test results correctly.

When Borrelia infects you, your immune system mounts an antibody response that evolves over time. IgM antibodies appear first, typically 1-2 weeks after infection, representing the early immune response. IgG antibodies develop later, usually 4-6 weeks after infection, but persist much longer — often for months or years, even after successful treatment.

This timing has important diagnostic implications. In early Lyme disease (first few weeks), IgM may be positive while IgG is still negative. By the time later manifestations develop — Lyme arthritis, neurological Lyme, cardiac Lyme — IgG should be strongly positive. A patient with symptoms suggesting late Lyme disease who has negative IgG almost certainly doesn’t have Lyme as the cause.

Testing for Lyme antibodies follows a standardized two-tier protocol: an initial screening test (usually ELISA or similar immunoassay) followed by a confirmatory Western blot if the screen is positive or equivocal. This approach reduces false positives that can occur with screening tests alone.

Order Your Lyme Disease Panel

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Key Benefits of Testing

Lyme IgG testing is essential for diagnosing Lyme disease beyond the first few weeks of infection. While early Lyme (erythema migrans rash occurring days to weeks after bite) can often be diagnosed clinically without testing, later stages require serological confirmation.

For suspected later-stage Lyme disease, IgG testing is the key test. Lyme arthritis, neurological Lyme (meningitis, facial palsy, radiculopathy), and cardiac Lyme typically develop weeks to months after infection — by which time IgG should be robustly positive. A negative IgG in someone with months of symptoms essentially excludes Lyme as the cause.

For ambiguous early presentations, combined IgG/IgM testing clarifies the picture. Someone presenting a few weeks after possible exposure might have early infection (IgM positive, IgG negative or weakly positive) or established infection (both positive). The antibody profile helps determine disease stage.

For epidemiological assessment, IgG testing reveals past exposure. In endemic areas, many people have positive IgG from prior infection (treated or possibly asymptomatic) — this reflects past exposure, not necessarily current disease. Understanding that positive IgG can persist years after resolved infection prevents misattributing current symptoms to Lyme.

For treatment monitoring context, while antibodies don’t reliably reflect treatment response (IgG persists long after successful treatment), the testing provides baseline documentation and helps rule out reinfection versus persistent infection debates.

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What Does Lyme IgG Testing Measure?

Lyme IgG testing detects IgG antibodies directed against proteins of Borrelia burgdorferi. The testing typically follows the CDC-recommended two-tier protocol.

Two-Tier Testing Protocol

Tier 1: Screening Test (ELISA or EIA)

The first tier is a sensitive screening test — usually an enzyme-linked immunosorbent assay (ELISA) or enzyme immunoassay (EIA). This test detects antibodies against Borrelia antigens with high sensitivity but imperfect specificity. Possible results:

• Negative: Testing stops. Lyme disease is unlikely (with important caveats about timing).
• Positive or Equivocal: Proceed to tier 2 for confirmation.

Tier 2: Confirmatory Test (Western Blot)

The Western blot separates Borrelia proteins by size and detects antibodies against specific proteins (bands). IgG Western blot is considered positive if antibodies react with at least 5 of 10 specified bands. This specificity requirement reduces false positives from cross-reacting antibodies.

Modified Two-Tier Testing (MTTT)

Updated CDC guidance now allows an alternative approach: using two different EIA/ELISA tests sequentially instead of ELISA followed by Western blot. This approach has comparable accuracy with faster turnaround and potential for automation.

Timing of Antibody Development

Understanding when IgG appears is crucial for interpretation:

Week 1-2 after infection: Antibodies typically not yet detectable. Testing during this window often yields false negatives.

Week 2-4: IgM begins appearing. IgG may still be negative or weakly positive.

Week 4-6: IgG becomes detectable and rises. Both IgM and IgG may be positive.

Week 6+: IgG should be solidly positive if infection is present. IgM may begin declining.

Months to years: IgG persists long-term, often for years after successful treatment. IgM usually (but not always) declines to negative.

What the Test Reports

Results are typically reported as:

• ELISA: Positive, negative, or equivocal/borderline (often with numeric value)
• Western blot (if performed): Positive or negative based on band criteria, often listing which bands are reactive
• Overall interpretation: Positive, negative, or indeterminate based on two-tier criteria

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Why Lyme IgG Testing Matters

Diagnosing Later-Stage Lyme Disease

While early Lyme disease (erythema migrans rash) can be diagnosed clinically, later manifestations require serological confirmation:

Lyme arthritis: Typically develops months after initial infection. Presents as episodic swelling of large joints (especially knee). IgG is virtually always strongly positive — a negative IgG essentially excludes Lyme arthritis.

Neurological Lyme: Can include meningitis, cranial nerve palsies (especially facial palsy), radiculopathy, or encephalopathy. IgG should be positive in serum; testing CSF may also be indicated for CNS involvement.

Cardiac Lyme: Heart block or myocarditis occurring weeks after infection. IgG should be positive.

Late Lyme: Months to years after infection, may include persistent arthritis, subtle cognitive issues, or polyneuropathy. IgG is consistently positive.

Geographic Considerations

Lyme disease is not uniformly distributed. In North America, it’s concentrated in the Northeast, mid-Atlantic, upper Midwest (Wisconsin, Minnesota), and Pacific coastal areas. Testing makes most sense when there’s plausible exposure:

High-endemic areas: Testing is appropriate with compatible symptoms; pre-test probability is reasonable.

Non-endemic areas: Without travel to endemic areas or tick exposure history, positive results may more likely represent false positives than true infection. Clinical context matters greatly.

In Europe, different Borrelia species (B. afzelii, B. garinii) cause Lyme disease, sometimes with different clinical manifestations. Testing approaches are similar but may use different antigens.

Distinguishing Past from Present Infection

A major interpretive challenge: IgG persists long after successful treatment. A positive IgG means someone was infected at some point — not necessarily that current symptoms are due to active Lyme disease.

In endemic areas, 5-10% of the population may have positive Lyme IgG from past infection. If someone with chronic fatigue living in Connecticut tests positive for Lyme IgG, it might reflect past resolved infection rather than explaining current symptoms. Clinical correlation is essential.

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What Can Affect Lyme IgG Results?

Factors That May Cause False Negatives

Testing too early: The most common reason for false negatives. IgG takes 4-6 weeks to develop. Testing during the first weeks of infection often misses antibodies that would be detectable later. If clinical suspicion remains high despite negative early testing, repeat testing in 2-4 weeks may be warranted.

Early antibiotic treatment: Antibiotics given very early in infection may blunt the antibody response, potentially causing persistent seronegativity despite past infection. This is relatively uncommon but recognized.

Immunosuppression: Patients with impaired immune systems may have diminished antibody responses to any infection, including Lyme.

Factors That May Cause False Positives

Cross-reacting antibodies: Antibodies from other infections may cross-react with Borrelia antigens, causing false-positive screening tests. This is why two-tier testing exists — the Western blot confirmation reduces this problem. Conditions that can cause cross-reactivity include:

• Other spirochetal infections (syphilis, leptospirosis, relapsing fever)
• Some viral infections (EBV, HIV)
• Autoimmune conditions
• Endocarditis

Testing in non-endemic areas without clear exposure: When pre-test probability is low, even reasonably specific tests produce more false positives than true positives (Bayesian probability).

Past resolved infection: Not a “false positive” technically, but IgG from years-ago infection may be misattributed to current symptoms.

The Seronegative Lyme Controversy

Some patients and practitioners believe in “seronegative Lyme disease” — Lyme infection without detectable antibodies. While false negatives do occur (especially early), robust scientific evidence does not support the concept of chronic seronegative Lyme disease. Patients with months to years of symptoms attributed to Lyme who remain consistently seronegative most likely don’t have Lyme disease, and alternative diagnoses should be pursued.

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Understanding Your Results

Interpreting Two-Tier Results

ELISA negative: Lyme disease unlikely. If symptoms strongly suggest early Lyme and testing was done within first 2-3 weeks, consider repeat testing in 2-4 weeks.

ELISA positive/equivocal, Western blot IgG negative: Likely false-positive screening test. Current Lyme disease unlikely. May reflect very early infection if IgM Western blot is positive (see Lyme IgM).

ELISA positive, Western blot IgG positive (≥5 bands): Confirms Borrelia infection occurred at some point. If symptoms are compatible, supports Lyme disease diagnosis. If symptoms are non-specific and chronic, past infection remains possible — clinical correlation needed.

Combining IgG and IgM Results

IgM positive, IgG negative: Suggests early infection (first 4-6 weeks) OR false-positive IgM. IgM alone is prone to false positives; interpret cautiously unless clinical picture strongly suggests early Lyme.

IgM positive, IgG positive: Suggests active or recent infection (within weeks to few months). Both antibody classes present supports genuine infection.

IgM negative, IgG positive: The most common pattern in later-stage Lyme. IgM has waned while IgG persists. Can also represent past resolved infection if current symptoms don’t fit Lyme.

Both IgM and IgG negative: Lyme disease very unlikely (with caveat about testing too early).

The Importance of Clinical Context

Lyme serology is not a standalone diagnostic — it must be interpreted in clinical context:

• What is the geographic exposure risk?
• Was there known tick bite or tick-infested area exposure?
• Do symptoms fit known Lyme disease manifestations?
• What is the timing of symptoms relative to possible exposure?
• Have alternative diagnoses been appropriately considered?

A positive IgG in someone with classic Lyme arthritis in Connecticut strongly supports the diagnosis. The same positive IgG in someone with vague chronic symptoms in Arizona (non-endemic) without tick exposure likely represents a different situation entirely.

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Health Connections

Lyme Arthritis

IgG findings: Strongly positive, often with robust responses to multiple bands on Western blot. Among the highest antibody levels seen in Lyme disease. A negative IgG essentially excludes Lyme arthritis.

Neurological Lyme Disease

IgG findings: Positive in serum. When CNS involvement is suspected (meningitis, encephalopathy), testing CSF for Lyme antibodies and comparing to serum levels (intrathecal antibody index) adds diagnostic value.

Early Lyme Disease (Erythema Migrans)

IgG findings: May be negative if tested in first few weeks. Early Lyme with classic erythema migrans rash is a clinical diagnosis that doesn’t require serological confirmation. Treating based on clinical presentation is appropriate.

Post-Treatment Lyme Disease Syndrome (PTLDS)

IgG findings: Typically positive (reflecting past documented infection). PTLDS refers to persistent symptoms after appropriately treated Lyme disease. The positive IgG doesn’t indicate persistent active infection — it simply confirms past infection. Antibody levels don’t correlate with or guide treatment of PTLDS.

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Why Testing Timing Matters

The single most important factor in Lyme serology interpretation is timing relative to infection:

Too early (first 2-3 weeks): Antibodies haven’t developed yet. Testing during this window produces false negatives. If you have a tick bite or erythema migrans rash, clinical treatment may be appropriate without waiting for serology to become positive.

Early-intermediate (3-6 weeks): IgM may be positive; IgG developing. This is a transition period where results can be ambiguous.

Established infection (>6 weeks): IgG should be clearly positive if Lyme is present. This is when IgG testing is most reliable.

Post-treatment (months to years later): IgG remains positive long after successful treatment. Don’t interpret persistent IgG as treatment failure — it’s expected normal behavior of the immune response.

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Related Biomarkers Often Tested Together

Lyme IgM — Early antibody response appearing 1-2 weeks after infection. Useful for early disease; more prone to false positives than IgG.

Lyme Western Blot — Confirmatory test identifying antibodies against specific Borrelia proteins. Reported as IgG and IgM components.

CBC — May show lymphocytosis in some cases of Lyme disease.

ESR and CRP — Inflammatory markers, often elevated in Lyme arthritis.

Rheumatoid Factor — May be ordered in arthritis workup to distinguish Lyme arthritis from rheumatoid arthritis.

CSF Analysis — When neurological Lyme is suspected, lumbar puncture with CSF Lyme antibodies and cell counts may be indicated.

Note: Information provided in this article is for educational purposes and doesn’t replace personalized medical advice.