False-Positive Results for Immunoglobulin M Serologic Results: Explanations and Examples

Extract

The false-positive rate of any diagnostic test is a function of the specificity of the test and prevalence of the disease in the population represented by the patient. For serologic assays, the presence of antibodies that cross-react with microbial antigens used in the assay or interfering substances that interact with assay components can also lead to false-positive results. Technical performance issues such as over-reading of weakly reactive bands on immunoblots can also lead to false-positive serologic tests results for microbes for which these assays are used (eg, Borrelia burgdorferi) [1]. Thus, positive IgM assay results can require cautious interpretation—consideration of clinical course compatibility and epidemiological factors—and/or confirmation by other serological or molecular testing methods. The issue of reactivation of IgM production against herpes viruses is beyond the scope of this review.

Cross-reacting Antibodies

Cross-reacting antibodies have been described for many infections. The association of acute human parvovirus infection with false-positive measles IgM was first described in Alaska in 1994 [2]. Subsequently, human parvovirus, rubella, and human herpesvirus (HHV) 6 infections have been described as causes of false-positive IgM test results for measles [3–7]. Human parvovirus infection has also been implicated in false-positive IgM assays for Epstein-Barr virus (EBV), herpes simplex virus, and HHV 6 virus infections [6, 8]. False-positive IgM serologic results for EBV (capsid antigen) and cytomegalovirus may occur in approximately 3% of patients with acute human immunodeficiency virus infection and 30% of patients with acute hepatitis A infection [9]. West Nile virus (WNV) is known to cross-react with St. Louis encephalitis virus and other flaviviruses [10].