Prospective study of serologic tests for lyme disease

Abstract

Background: Tests to determine serum antibody levels-the 2-tier sonicate immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and Western blot method or the IgG of the variable major protein-like sequence-expressed (VlsE) sixth invariant region (C6) peptide ELISA method-are the major tests available for support of the diagnosis of Lyme disease. However, these tests have not been assessed prospectively.

Methods: We used these tests prospectively to determine serologic responses in 134 patients with various manifestations of Lyme disease, 89 patients with other illnesses (with or without a history of Lyme disease), and 136 healthy subjects from areas of endemicity and areas in which the infection was not endemic.

Results: With 2-tier tests and the C6 peptide ELISA, only approximately one-third of 76 patients with erythema migrans had results that were positive for IgM or IgG seroreactivity with Borrelia burgdorferi in acute-phase samples. During convalescence, 3-4 weeks later, almost two-thirds of patients had seroreactivity with the spirochete B. burgdorferi. The frequencies of seroreactivity were significantly greater among patients with spirochetal dissemination than they were among those who lacked evidence of disseminated disease. Of the 44 patients with Lyme disease who had neurologic, heart, or joint involvement, all had positive C6 peptide ELISA results, 42 had IgG responses with 2-tier tests, and 2 patients with facial palsy had only IgM responses. However, among the control groups, the IgG Western blot was slightly more specific than the C6 peptide ELISA. The differences between the 2 test systems (2-tier testing and C6 peptide ELISA) with respect to sensitivity and specificity were not statistically significant.

Conclusions: Except in patients with erythema migrans, both test systems were sensitive for support of the diagnosis of Lyme disease. However, with current methods, 2-tier testing was associated with slightly better specificity.

Figure 1

Antibody titers to Borrelia burgdorferi by sonicate IgM (A) or IgG (B) ELISA are shown for patients with erythema migrans (acute and convalescent [Conv] phase), acute-phase neurologic or cardiac involvement (Acute neuro carditis), arthritis or late neurologic abnormalities (Arthritis late neuro), and post-infection symptoms (Post Lyme disease). The antibody titers were plotted on a logarithmic scale. For IgG determinations, a titer of >1 :400 was defined as positive, a titer of 1:200 or 1:400 was defined as indeterminate, and a titer <1:100 was defined as negative. For IgM determinations, a titer>1:200 was defined as positive, a titer 1:100 was defined as indeterminate, and a titer <1:100 was defined as negative. The absorbance values with an ELISA that employs a 26-mer peptide from the sixth invariant region (C6) of the variable major protein-like sequence-expressed (VlsE) lipoprotein of the spirochete are shown for the same patient groups (C). The absorbance values are plotted on an arithmetic scale. In all 3 panels, the horizontal bars indicate mean values for patients with positive responses, vertical bars indicate 1 SD, stipled areas indicate indeterminate range, and cross-hatched areas indicate negative range.