What does a positive IgM (immunoglobulin M) p23 result indicate?

What Does a Positive IgM p23 Mean?

A positive IgM antibody to the p23 (OspC) protein indicates recent or early Lyme disease infection, typically within the first 30 days of symptom onset. 1

Understanding the p23/OspC Antigen

The p23 band (also called the 21-24 kDa band) represents antibodies against OspC (Outer Surface Protein C), a major outer membrane protein of Borrelia burgdorferi that is highly immunogenic during early infection. 1, 2

• p23/OspC is one of the most immunodominant antigens in early Lyme disease, particularly eliciting strong IgM responses in the first weeks after tick bite 2
• The protein is expressed on the outer surface of the bacteria and varies in length and amino acid sequence between different Borrelia strains 1

Diagnostic Interpretation Algorithm

For Symptoms <30 Days Duration:

Step 1: Two-Tiered Testing Required 1

• Initial screening with EIA/ELISA for IgG and IgM antibodies
• If positive or equivocal, reflex to Western immunoblot for confirmation

Step 2: Western Immunoblot Criteria 1

• Positive IgM requires ≥2 of 3 bands present: 21-24 kDa (p23/OspC), 39 kDa, and 41 kDa
• The p23 band alone is insufficient for diagnosis—you need at least one additional band
• Critical pitfall: The 41 kDa band cross-reacts with other bacterial flagellar proteins and was found in 43% of healthy controls, so never interpret 41 kDa alone as positive 1

For Symptoms >30 Days Duration:

• IgM testing should NOT be performed after 30 days—it increases false-positive risk 1
• Use IgG Western immunoblot only (requires ≥5 of 10 specific bands) 1
• Most patients develop detectable IgG response beyond 30 days 1

Clinical Context Matters

When p23 IgM is Clinically Meaningful: 1

• Patient has erythema migrans rash or other early Lyme disease symptoms
• Symptom duration <30 days
• Epidemiologic exposure risk (endemic area, tick exposure)
• Positive two-tiered testing with appropriate band criteria met

When to Suspect False-Positive: 3

• IgM positive but clinical/epidemiologic findings don't fit
• Single band positivity or insufficient bands for criteria
• Symptoms >30 days (should have IgG response by then)
• IgM tests suffer disproportionately from false-positive results across all pathogens 3

Critical Pitfalls to Avoid

1. Never interpret p23 band alone as diagnostic—requires ≥2 of 3 IgM bands for positive result 1

2. Never order IgM testing beyond 30 days of symptoms—this dramatically increases false-positive rates and leads to misdiagnosis 1

3. Never skip the initial EIA screening—Western blot should NOT be performed unless EIA is positive or equivocal 1

4. Never overinterpret cross-reactive bands—the 41 kDa flagellin band is particularly problematic and found in many healthy individuals 1

5. Always consider convalescent-phase testing—some patients require acute and convalescent sera because sensitivity is decreased in the first weeks of infection 1

Strain Variation Considerations

• North American strain B31 (commonly used in commercial assays) does not express OspC well due to a genetic deletion, potentially reducing test sensitivity 2
• Strain 2591 from Connecticut expresses p23/OspC abundantly and shows strong IgM reactivity in early disease 2
• This variability between strains emphasizes why two-tiered testing with multiple antigens is essential rather than relying on single bands 1