Does a positive IgM (Immunoglobulin M) test for Lyme disease with 23kD and 39kD proteins indicate a current infection?

Positive IgM Western Blot with 23kD and 39kD Bands in Lyme Disease Diagnosis

A positive IgM Western blot with 23kD and 39kD bands alone is not sufficient to confirm a current Lyme infection, as IgM results are only interpretable within the first 4 weeks of illness and must show at least 2 of 3 specific bands (24kD, 39kD, and 41kD) to be considered positive. 1

Interpretation of IgM Western Blot Results

• According to the Infectious Diseases Society of America (IDSA) and American Society for Microbiology (ASM) guidelines, a positive IgM Western blot is considered positive only if 2 of the following 3 bands are present: 24kD, 39kD, and 41kD 1
• The IgM Western blot should only be performed during the first 4 weeks of illness and only after a positive or equivocal first-tier enzyme immunoassay (EIA) test 1
• IgM Western blot results are not interpretable after a patient has had symptoms for greater than 1 month's duration because the likelihood of a false-positive test result for current infection is high 1

Two-Tiered Testing Approach

• The recommended laboratory diagnosis for Lyme disease follows a two-tiered testing algorithm: a sensitive first test (EIA or indirect fluorescent antibody test) followed by Western immunoblot to confirm equivocal or positive results 1
• Testing should begin with an IgM and IgG EIA, and only if positive or equivocal should be followed by Western blot testing 1
• Performing Western immunoblot without a first-tier EIA is not recommended for clinical diagnosis, although it may be accepted for surveillance purposes 1

Limitations of IgM Testing

• IgM antibodies often persist for months or years after successfully treated or untreated infection, so seroreactivity alone cannot be used as a marker of active disease 1, 2
• Studies have shown that IgM or IgG antibody responses to B. burgdorferi may persist for 10-20 years, but these responses are not indicative of active infection 2
• Early antibiotic treatment can blunt the antibody response, potentially leading to false-negative results 1

Clinical Correlation is Essential

• Erythema migrans (EM) is the only manifestation of Lyme disease in the United States that is sufficiently distinctive to allow clinical diagnosis without laboratory confirmation 1
• For patients with EM, laboratory testing is not necessary, and treatment should be initiated based on the clinical presentation 1
• Pretest probability based on exposure history is crucial when interpreting Lyme disease test results 1
• In areas with low incidence of Lyme disease, positive serologic results have poor predictive value without a history of travel to endemic regions 1

Common Pitfalls in Lyme Disease Testing

• Misinterpreting isolated band patterns without considering the complete clinical picture 1
• Relying on IgM results beyond the 4-week window when they are no longer reliable indicators of current infection 1
• Using unvalidated tests or non-standard interpretation criteria that may lead to false-positive results 1
• Failing to consider the possibility of reinfection versus persistent antibody response from previous infection 1

Recommendations for Accurate Diagnosis

• For suspected early Lyme disease (symptoms <4 weeks), use the two-tiered approach with both IgM and IgG Western blots if the first-tier test is positive 1
• For suspected late Lyme disease (symptoms >4 weeks), only IgG Western blot should be performed following a positive first-tier test 1
• In cases of suspected reinfection, consider acute and convalescent serologic testing to detect an increase in EIA titer or an increase in the number of antibody bands 1
• Always interpret serologic results in the context of exposure history, clinical presentation, and duration of symptoms 1