Blood Markers Most Associated with Chronic Lyme Disease
The most significant blood markers associated with chronic Lyme disease are high IgG antibody titers, complement split product C4a, and C-reactive protein (CRP), with IgG antibodies being the primary diagnostic indicator.
Serological Markers in Chronic Lyme Disease
Antibody Response
- Patients with late/persistent Lyme infection (chronic Lyme disease) typically demonstrate high IgG antibody titers, especially in those with arthritis and acrodermatitis chronica atrophicans 1
- IgM antibodies are usually undetectable in chronic Lyme disease, found in only 10-40% of patients with late manifestations 1
- Intrathecal antibody production is a key marker in chronic neuroborreliosis and represents the most important microbiological diagnostic criterion for this manifestation 1
Two-Tiered Testing Approach
- The standard diagnostic approach involves a two-tiered testing strategy:
- First tier: Enzyme immunoassay (EIA) or indirect fluorescent antibody test
- Second tier: Western immunoblot for confirmation of positive or equivocal first-tier results 1
- For chronic Lyme disease (symptoms >30 days), IgG Western immunoblot alone is typically sufficient as most patients have a detectable IgG response beyond 30 days 1
- A positive IgG Western blot result requires the presence of ≥5 of 10 specific bands (18,21-24,28,30,39,41,45,58,66, and 93 kDa) 1
Inflammatory and Immune Markers
Complement System Markers
- C4a levels are significantly elevated in patients with chronic Lyme disease who have predominant musculoskeletal symptoms 2
- C4a levels correlate with treatment response in chronic Lyme disease - decreasing with successful antibiotic therapy and increasing with lack of response 2
- C3a levels are typically normal in chronic Lyme disease patients, which differs from the pattern seen in acute Lyme disease 2
Acute Phase Proteins
- C-reactive protein (CRP) levels may be elevated in chronic Lyme disease, particularly in patients with antibiotic-refractory Lyme arthritis and post-treatment Lyme disease syndrome 3
- In a preliminary study, 86% of Lyme disease patients had abnormally high concentrations of serum CRP (range 14-158 mg/L) 4
- Serum amyloid A (SAA) levels are typically not elevated in later stages of Lyme disease, including chronic manifestations 3
Cytokines and Chemokines
- Several inflammatory markers have been identified in antibiotic-refractory Lyme arthritis, including:
- Interleukins: IL-6, IL-8, IL-10, IL-1β, IL-23, IL-17F
- Other cytokines: TNFα, IFNγ
- Chemokines: CXCL9, CXCL10, CCL2, CCL3, CCL4 5
- Cytokines and chemokines related to the Th17 pathway may be particularly relevant in predicting antibiotic-refractory Lyme arthritis 5
Clinical Pitfalls in Laboratory Testing
- Antibodies often persist for months or years after successfully treated or untreated infection, making seroreactivity alone insufficient as a marker of active disease 1
- Neither positive serologic test results nor a history of previous Lyme disease ensures protective immunity; repeated infection with B. burgdorferi has been reported 1
- Overinterpreting a small number of antibody bands on Western blot can lead to reduced specificity and potential misdiagnosis 1
- PCR testing has limited clinical utility due to low sensitivity, particularly for blood and CSF samples, and potential for contamination 1
Diagnostic Approach for Suspected Chronic Lyme Disease
Confirm previous Borrelia burgdorferi infection through documented:
- Previous erythema migrans rash diagnosed by a physician, OR
- Positive two-tiered serologic testing 1
For neurologic manifestations:
- Test for intrathecal antibody production in CSF
- CSF and serum should be collected on the same day and diluted to match total protein or IgG concentration
- A CSF/serum IgG EIA optical density ratio >1.0 indicates active intrathecal antibody production 1
For musculoskeletal manifestations:
For monitoring treatment response: