Role of Serology in the Diagnosis of Lyme Disease

Abstract

Numerous concerns regarding the potential for misdiagnosis of Lyme disease using commercial assays have been voiced by the US Food and Drug Administration (FDA). We attempted to clarify the clinical value of serologic testing for Lyme disease using the results of commonly marketed assays for detecting antibody to Borrelia burgdorferi, the organism that causes Lyme disease. We reviewed published studies on B burgdorferi test performance published through 1998, package insert labeling from FDA-cleared test kits for B burgdorferi, and Lyme Disease Survey Set LY-A from the College of American Pathologists. We assessed the sensitivity and specificity of commercial serologic tests (enzyme-linked immunosorbent assay [ELISA], immunofluorescence antibody [IFA], and immunodot) for diagnosis of Lyme disease. To reduce this risk of misdiagnosis, it is important that clinicians understand the performance characteristics and limitations of these tests. These tests, in common use in clinical or commercial laboratories, should be used only to support a clinical diagnosis of Lyme disease, not as the primary basis for making diagnostic or treatment decisions. Serologic testing is not useful early in the course of Lyme disease because of the low sensitivity of tests in early disease. Serologic testing may be more useful in later disease, at which time sensitivity and specificity of the test are improved. Positive or equivocal results on an ELISA, IFA, or immunodot assay requires supplemental testing with a Western blot assay. A negative result on the Western blot or ELISA indicates that there is no serologic evidence of infection by B burgdorferi at the time the sample was drawn.

Evaluation of Two Commercial Systems for Automated Processing, Reading, and Interpretation of Lyme Borreliosis Western Blots

“…Preliminary studies in our laboratory have demonstrated considerable variation in Lyme WB results when strips are visually read by different laboratory technologists (M. Binnicker, unpublished data). This variation in WB results may contribute to inaccurate diagnoses, resulting in various consequences to patients, as described in past studies (4,13,14,17). Therefore, an important need of clinical laboratories is to enhance the objectivity and consistency of Lyme WB interpretation.…”

Antigenicity of borrelial protein BBK32 fragments in early Lyme borreliosis

“…When used to assess the first line of antibody response in LB, IgM serology is often prone to specificity problems due to cross-reactive antibodies from other infections (Brown et al, 1999).…”

“…For serologic confirmation of Borrelia burgdorferi infection, a two-step approach with ELISA as a screening test and Western blotting as a confirmatory test is recommended by the Centers for Disease Control (CDC) (Brown et al, 1999). This approach has been challenged not only because it is labour-intensive and time-consuming, but also because the criteria for a positive Western blot vary according to which Borrelia strains are used as antigens and to local variations in the infective species of Borrelia (Robertson et al, 2000).…”

Identification of Borrelia burgdorferi Ribosomal Protein L25 by the Phage Surface Display Method and Evaluation of the Protein's Value for Serodiagnosis

“…For serodiagnosis, a two-step process, including an enzyme-linked immunosorbent assay (ELISA) followed by Western immunoblot analysis, is recommended in Europe and the United States. Serological tests are widely used despite several shortcomings, such as the heterogeneity of antigen preparations and a lack of standardization causing interlaboratory variation (3,23). Furthermore, serological tests show insensitivity in the early stages of LB (1,13).…”