What does a positive Lyme IgG (Immunoglobulin G) antibody test result indicate and how is it treated?

What a Positive Lyme IgG Antibody Indicates

A positive Lyme IgG antibody test alone does NOT confirm active Lyme disease and must be interpreted in the context of clinical symptoms, exposure history, and proper two-tiered testing methodology. 1

Understanding IgG Positivity

IgG antibodies indicate past or current exposure to Borrelia burgdorferi, not necessarily active infection. The timing and clinical context are critical:

Timing of IgG Response

• IgG antibodies typically develop from approximately the sixth week after infection, following the initial IgM response 1
• In early disseminated infection (Stage II), IgG antibodies become predominant over IgM 1
• In late/persistent infection (Stage III), patients usually demonstrate high IgG antibody titers, particularly with arthritis and acrodermatitis 1, 2

Critical Diagnostic Pitfall: Antibody Persistence

• IgG antibodies persist for months or years after successfully treated or even untreated infection, making seroreactivity alone insufficient as a marker of active disease 2
• Approximately 20% of healthy patients who experienced Lyme disease in the past remain seropositive for months to years 3
• Positive serology does not indicate protective immunity, and reinfection with B. burgdorferi can occur despite prior infection 2

Proper Interpretation Requires Two-Tiered Testing

A positive IgG result is only valid when confirmed through the complete two-tiered testing algorithm:

First-Tier Test

• Enzyme immunoassay (EIA) or immunofluorescence assay serves as the screening test 1, 2
• If negative, testing stops—Lyme disease is unlikely 1

Second-Tier Confirmation (Western Immunoblot)

• A positive IgG Western blot requires ≥5 of 10 specific bands (18,21-24,28,30,39,41,45,58,66, and 93 kDa) 1, 2
• Fewer than 5 IgG bands does NOT constitute a positive result 1
• The 41-kDa band alone is meaningless—it cross-reacts with other bacterial flagellar proteins and was found in 43% of healthy controls 1

Common Testing Errors Leading to Misdiagnosis

• Overinterpreting a small number of antibody bands leads to reduced specificity and false-positive diagnoses 1, 2
• Many commercial kits have heterogeneous and often unknown diagnostic properties 1
• Cross-reactivity occurs with other spirochetal infections (particularly syphilis), Epstein-Barr virus, cytomegalovirus, and other bacterial infections 1

Clinical Context Is Mandatory

Positive antibody testing without corresponding clinical symptoms is NOT sufficient for diagnosing Lyme disease: 1

Required Clinical Elements

• Document objective clinical manifestations consistent with Lyme disease stages 1
• Obtain detailed exposure history including geographic location and tick exposure risk 1
• For suspected reinfection, perform thorough skin examination for erythema migrans, as most reinfection cases present with this rash 1

Stage-Specific IgG Interpretation

• Symptoms <30 days: Both IgM and IgG Western blots should be performed; IgG may still be developing 1
• Symptoms >30 days: IgG Western blot alone is typically sufficient; IgM testing at this stage increases false-positive risk 1
• Late manifestations: High IgG titers are expected, but IgM is usually undetectable (found in only 10-40% of cases) 1, 2

Special Considerations for Neurologic Disease

For suspected Lyme neuroborreliosis with positive IgG:

• Test for intrathecal antibody production in cerebrospinal fluid (CSF) 1, 2
• Collect CSF and serum on the same day and dilute to match total protein or IgG concentration 1, 2
• A CSF/serum IgG EIA optical density ratio >1.0 indicates active intrathecal antibody production, which is highly specific for neuroborreliosis 1, 2
• In the United States, serum antibody presence in appropriate clinical settings is highly sensitive and specific for Lyme neuroborreliosis 1

What NOT to Do

• Do not treat based on positive IgG serology alone without clinical symptoms 1, 3
• Do not interpret isolated bands or fewer than the required number of bands as positive 1
• Do not use PCR on blood for routine diagnosis—it has poor sensitivity and high contamination risk 1
• Do not assume positive serology indicates active infection requiring treatment in asymptomatic individuals 3
• Avoid long-term or cycling antibiotic regimens based solely on positive serology in patients with nonspecific symptoms 3