What is the difference between IgM and IgG as acute infection markers?

IgM is the Acute Infection Marker, IgG Indicates Past Infection or Immunity

IgM antibodies appear early during acute infection and typically decline within 6 months, while IgG antibodies develop later and persist long-term, indicating either past infection or immunity from vaccination. 1

Temporal Dynamics of Antibody Responses

IgM Antibody Characteristics

• IgM appears at symptom onset or within 5-10 days before symptoms begin in acute viral infections 1, 2
• IgM remains detectable for approximately 6 months after acute infection, then declines to undetectable levels in most patients 1, 2
• IgM is the most reliable serologic marker for distinguishing acute from chronic infection 3, 4
• In hepatitis B specifically, IgM anti-HBc appears during acute or recent infection and persists for about 6 months 1
• In hepatitis A, IgM anti-HAV becomes detectable 5-10 days before symptom onset and generally declines to undetectable levels within 6 months 2

IgG Antibody Characteristics

• IgG becomes detectable approximately 1-4 weeks after symptom onset and persists at high levels long-term 1
• IgG indicates either past resolved infection with natural immunity or immunity from vaccination 2, 3
• IgG antibodies from natural infection persist for life and confer protection against reinfection 2
• After vaccination, protective IgG levels persist for at least 20-40 years according to kinetic models 2

Clinical Interpretation Algorithm

For Acute Infection Diagnosis

• Positive IgM + Negative or Low IgG = Acute/Recent Infection (within past 6 months) 1, 2, 4
• Negative IgM + Positive IgG = Past Infection or Vaccination Immunity 2, 3
• Positive IgM + Positive IgG = Acute infection with developing immunity or recent infection (timing depends on when IgG appeared) 1

Specific Disease Examples from Guidelines

Hepatitis A:

• Acute infection: IgM anti-HAV positive 1
• Past infection/immunity: IgM anti-HAV negative + total anti-HAV positive 2

Hepatitis B:

• Acute infection: HBsAg positive + IgM anti-HBc positive 1, 3, 4
• Chronic infection: HBsAg positive + IgM anti-HBc negative 3, 4
• Resolved infection: HBsAg negative + total anti-HBc positive (IgG) 3

Hepatitis E:

• Acute infection: IgM anti-HEV positive (appears 4-6 weeks post-exposure, lasts 2-4 months) 1
• Past infection: IgG anti-HEV positive (detectable by 4 weeks after presentation) 1

Critical Clinical Pitfalls

False-Positive IgM Results

• IgM testing has low positive predictive value in asymptomatic populations with low disease prevalence 1, 3, 4
• Restrict IgM testing to patients with clinical hepatitis or epidemiologic exposure to avoid false-positives 3, 4
• False-positive HAV IgM can occur in populations with low hepatitis A prevalence 1

IgM Persistence in Chronic Disease

• In chronic hepatitis B, low-level IgM anti-HBc can persist during viral replication or disease exacerbations, potentially causing diagnostic confusion 4
• This does not indicate acute infection but rather chronic disease activity 4

Delayed or Absent Antibody Responses

• Immunosuppressed patients (e.g., organ transplant recipients) may have delayed humoral responses, requiring molecular testing (PCR/NAAT) instead of serology 1
• In hepatitis E among transplant recipients, HEV RNA detection may be necessary when antibody responses are delayed 1

Practical Testing Recommendations

When to Order IgM vs IgG

• Order IgM when evaluating acute illness with compatible symptoms (within days to weeks of onset) 1, 4
• Order IgG to assess immunity status before vaccination or to confirm past infection 2, 3
• Order both IgM and IgG together when timing of infection is uncertain or to differentiate acute from past infection 1

Optimal Specimen Handling

• Both IgM and IgG testing require serum or plasma specimens 1
• Transport at room temperature within 2 hours for optimal results 1
• Use EDTA or plasma preparation tubes for plasma; clot or serum separator tubes for serum 1