Peer-Reviewed Literature Synthesis

Lyme Disease Biomarker Atlas

Serologic, cerebrospinal fluid, molecular, and inflammatory biomarkers in Borrelia burgdorferi infection — from early localized disease through disseminated, neuroborreliosis, and post-treatment persistent symptom phenotypes.

Literature Overview

Lyme disease diagnosis relies primarily on two-tier serology per CDC/IDSA guidelines. CSF biomarkers support neuroborreliosis. No validated biomarker distinguishes post-treatment Lyme disease syndrome (PTLDS) from other fatiguing illnesses.

2-tier
CDC-recommended serology
C6
VisE peptide ELISA
CSF
CXCL13 for neuroborreliosis
IgM/IgG
Stage-dependent response

Two-Tier Serology

EIA screening followed by IgM/IgG immunoblot confirmation. Sensitivity improves with disease duration; early EM may be seronegative.

  • EIA (whole-cell or C6)
  • IgM WB: ≥2 of 3 bands
  • IgG WB: ≥5 of 10 bands

CSF & Neuroborreliosis

Intrathecal antibody production and lymphocytic pleocytosis support CNS involvement. CXCL13 is a highly specific CSF chemokine marker.

  • CSF anti-Bb antibody index
  • CSF CXCL13 elevation
  • Lymphocytic pleocytosis

Chronic / PTLDS Phenotype

Persistent symptoms after standard therapy overlap with ME/CFS. Inflammatory and chemokine markers are research-stage only.

  • IL-6, IL-10, IFN-γ alterations
  • CCL19, CXCL13 (serum research)
  • No FDA-validated chronic panel

Searchable Alterations Database

HC = healthy controls; EM = erythema migrans; NB = neuroborreliosis; PTLDS = post-treatment Lyme disease syndrome.

Overlap with ME/CFS & Long COVID

PTLDS and chronic Lyme symptom profiles overlap substantially with ME/CFS (fatigue, PEM, cognitive dysfunction). Shared inflammatory and autonomic biomarkers may appear in both conditions. See the ME/CFS Biomarker Atlas for fatigue-dominant markers not specific to Borrelia exposure.

Stage-dependent serology (CDC two-tier algorithm)

IgM antibodies peak in early disseminated disease (weeks 2–4); IgG antibodies develop over weeks to months and persist for years. Early localized EM (<30 days) may be seronegative — clinical diagnosis with epidemiologic risk is essential. Two-tier testing is not recommended for screening asymptomatic individuals.

Marker / TestDirectionCategoryvs. ComparisonClinical ContextKey Reference

Category Deep Dives

🩸 Two-Tier Serology Panel

  • B. burgdorferi EIA (screening)↑ positive
  • IgG immunoblot (≥5/10 bands)↑ disseminated
  • IgM immunoblot (≥2/3 bands)↑ early
  • C6 peptide ELISA (VisE)↑ sensitive
  • Anti-VlsE antibodies↑

🧠 CSF Neuroborreliosis Markers

  • CSF CXCL13↑ highly specific
  • CSF anti-Bb antibody index↑ intrathecal
  • CSF lymphocytic pleocytosis↑
  • CSF protein elevation↑
  • CSF oligoclonal bands↕ subset

🔥 Inflammatory & Immune Markers

  • IL-6↑ active disease
  • IL-10↑
  • IFN-γ↑
  • CRP↕ variable
  • CCL19↑ research

🔄 Chronic Lyme / PTLDS Research

  • Serum CXCL13↕ research
  • PBMC cytokine profileAltered
  • Anti-neuronal antibodies↕ subset
  • Heart rate variability↓ ME/CFS overlap

Key References

CDC Guidelines

Recommendations for Test Performance and Interpretation — Two-Tier Testing

CDC Lyme Disease — Two-tier serologic testing algorithm
CDC Lab Testing →
CDC Recommendation — Serology

Updated CDC Recommendation for Serologic Diagnosis of Lyme Disease

Mead P et al. MMWR Morb Mortal Wkly Rep. 2019;68(32):703 — Two-tier EIA/immunoblot testing
DOI: 10.15585/mmwr.mm6832a4 →
Clinical Practice Guideline

IDSA/AAN/ACR 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease

Lantos PM et al. Clin Infect Dis. 2021;72(1):e1–e48 — Serologic testing, CSF antibody index, PCR
DOI: 10.1093/cid/ciaa1215 →
Primary Study — C6 ELISA

Serodiagnosis of Lyme Disease by Kinetic ELISA Using Recombinant VlsE1 or Peptide Antigens of Borrelia burgdorferi Compared with 2-Tiered Testing

Bacon RM et al. J Infect Dis. 2003;187(8):1187–99 — VlsE1 and C6 peptide ELISA performance
DOI: 10.1086/374395 →
Primary Study — CSF CXCL13

The chemokine CXCL13 (BLC): a putative diagnostic marker for neuroborreliosis

Rupprecht TA et al. Neurology. 2005;65(3):448–50 — CSF chemokine specificity
DOI: 10.1212/01.wnl.0000171349.06645.79 →
Primary Study — Serum Mediators

Serum Inflammatory Mediators as Markers of Human Lyme Disease Activity

Soloski MJ et al. PLoS One. 2014;9(4):e93243 — CCL19, IL-6 and CRP elevated in acute Lyme vs healthy controls
DOI: 10.1371/journal.pone.0093243 →
Review — Co-infections

Coinfections Acquired from Ixodes Ticks

Swanson SJ et al. Clin Microbiol Rev. 2006;19(4):708–27 — Anaplasma and Babesia co-infection with Lyme disease
DOI: 10.1128/CMR.00011-06 →
Disclaimer: Educational synthesis only — not medical advice. Lyme diagnosis requires clinical correlation with exposure history and compatible symptoms. Serologic tests have well-documented limitations in early disease. No chronic Lyme biomarker panel is FDA-validated. Consult infectious disease specialists for interpretation.

Individual Lyme Disease biomarker pages

Each Lyme Disease marker has its own page with direction, comparison group, symptoms, test details, citation and FAQ. Browse all marker pages.

CSF

Chronic/PTLDS

Co-infection

Functional

Inflammatory

Molecular

Serologic

Cite this page

Reusing these data? Please cite the tracker so others can find the source.

Open Source Medicine Foundation. (2026). Lyme Disease Biomarkers: 36 Blood Tests & Lab Markers. Research Tracker. https://research.opensourcemed.info/lyme-biomarkers.html (accessed )

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