IgM vs IgG Antibody Testing: Which to Order
For most clinical scenarios, order both IgM and IgG antibody tests together, as the combination significantly improves diagnostic sensitivity and provides critical information about the timing and stage of infection. 1
Disease-Specific Testing Recommendations
For Lyme Disease (Borrelia burgdorferi)
- Order both IgM and IgG Western blot if symptoms have been present for <30 days, as IgM appears first and is generally directed at the most immunogenic antigens 1
- Order IgG Western blot only if symptoms have been present for >30 days, as most patients have detectable IgG response beyond this timeframe and IgM testing increases false-positive risk 1
- The two-tier testing approach (EIA screening followed by Western blot confirmation) requires both IgM and IgG during the early phase to avoid missing acute infections 1
For MOG-Associated Disorders (Encephalomyelitis/Optic Neuritis)
- Order MOG-IgG testing only using cell-based assays with full-length human MOG antigen 1, 2
- Do NOT order MOG-IgM or MOG-IgA testing, as the clinical relevance of isolated IgM or IgA results is unknown and testing for IgM requires removal of total IgG to avoid false results 1
- Use Fc-specific or IgG1-specific secondary antibodies to avoid cross-reactivity with IgM and IgA 1, 2
For COVID-19/SARS-CoV-2
- Order combined IgM/IgG testing when used as an adjunct to RT-PCR, as the combined assay has better utility and sensitivity (98.6%) compared to single tests 1
- IgM and IgA antibodies appear around 5 days post-symptom onset, while IgG appears around 14 days 1
- Be aware that rapid IgM/IgG tests have poor sensitivity (18.4%) in acute patients and should not replace RT-PCR for diagnosis 1
For Anaplasmosis and Ehrlichiosis
- Order both acute and convalescent IFA titers for both IgG and IgM antibodies to detect four-fold or greater rise in titer 1
- Single timepoint testing may miss acute infections due to delayed antibody response 1
Critical Timing Considerations
Early Infection (<2 weeks)
- IgM antibodies appear first and indicate acute or recent infection 1
- Order both IgM and IgG to maximize sensitivity during the window period when IgG may still be negative 1
- Some patients require both acute-phase and convalescent-phase serologic analysis due to decreased sensitivity in the first weeks 1
Late Infection (>30 days)
- IgG antibodies predominate and persist longer 1
- IgM testing becomes less useful and increases false-positive risk in this timeframe 1
- Focus on IgG testing alone unless there is concern for reinfection 1
Common Pitfalls to Avoid
False-Positive IgM Results
- IgM antibodies can cross-react with non-specific antigens (e.g., the 41-kDa band in Lyme testing was found in 43% of healthy controls) 1
- Ordering IgM testing beyond 30 days of symptom onset significantly increases false-positive rates 1
- Specific IgM assays for viral agents may produce false positives, especially with high titers of IgG antibodies 1
Interpretation Errors
- Never interpret fewer bands than required as positive (e.g., for Lyme IgM Western blot, ≥2 of 3 bands required; for IgG, ≥5 of 10 bands required) 1
- Always interpret results in clinical context, as isolated antibody positivity without compatible symptoms can be misleading 1
Technical Considerations
- For MOG testing, using non-Fc-specific secondary antibodies can cause cross-reactivity with IgM and IgA, leading to false results 1
- Antibody titers fluctuate with disease activity and treatment status; consider retesting during acute attacks or treatment-free intervals if initial testing is negative 1, 2
Practical Algorithm
Determine symptom duration:
- <30 days → Order both IgM and IgG
30 days → Order IgG only (except for specific diseases like MOG where only IgG is ever indicated)
Consider disease-specific guidelines:
Plan for convalescent testing:
- If pretest probability is low-to-moderate, measure antibodies at presentation and 2-3 weeks later to assess for four-fold rise 1