A Community Study of Borrelia burgdorferi Antibodies among Individuals with Prior Lyme Disease in Endemic Areas

Abstract

The objective was to examine the prevalence of Borrelia antibodies among symptomatic individuals with recent and past Lyme disease in endemic communities using standard assays and novel assays employing next-generation antigenic substrates. Single- and two-tiered algorithms included different anti-Borrelia ELISAs and immunoblots. Antibody prevalence was examined in sera from 32 individuals with recent erythema migrans (EM), 335 individuals with persistent symptoms following treatment for Lyme disease (PTLS), and 41 community controls without a history of Lyme disease. Among convalescent EM cases, sensitivity was highest using the C6 ELISA (93.8%) compared to other single assays; specificity was 92.7% for the C6 ELISA vs. 85.4–97.6% for other assays. The two-tiered ELISA-EUROLINE IgG immunoblot combinations enhanced case detection substantially compared to the respective ELISA-IgG Western blot combinations (75.0% vs. 34.4%) despite similar specificity (95.1% vs. 97.6%, respectively). For PTLS cohorts, two-tier ELISA-IgG-blot positivity ranged from 10.1% to 47.4%, depending upon assay combination, time from initial infection, and clinical history. For controls, the two-tier positivity rate was 0–14.6% across assays. A two-tier algorithm of two-ELISA assays yielded a high positivity rate of 87.5% among convalescent EM cases with specificity of 92.7%. For convalescent EM, combinations of the C6 ELISA with a second-tier ELISA or line blot may provide useful alternatives to WB-based testing algorithms.

Anti-lysoganglioside and other anti-neuronal autoantibodies in post-treatment Lyme Disease and Erythema Migrans after repeat infection

“…It is possible that there was variation in the level of autoantibodies based on the Bb serostatus of the individuals within the LD case groups. We examined the distribution of antineuronal autoantibodies and serum activation of CaMKII activity in cases testing negative vs positive for Bb antibodies using two classification methods - the single tier C6 ELISA (C6 ELISA) and the more specific two-tier algorithm (C6 ELISA and EUROLINE –RN-AT IgG) as described previously ( Strobino et al., 2018 ). Bb serostatus at the time of sample collection was not associated with significant differences in autoantibodies or CaM kinase activation, regardless of whether serostatus was categorized based on the C6 ELISA alone or the two-tier algorithm.…”

“…Stored serum samples from a community serosurvey conducted in hyperendemic LD areas of New York, New Jersey, and Connecticut were examined; the NYS Psychiatric Institute IRB approved the study sample collection and all participants signed informed consent ( Strobino et al., 2018 ). Clinical details of LD history were obtained through questionnaires at the time of the survey and through follow-up telephone contact to obtain additional information.…”

“…A total of 179 individual samples were included in this study, drawn from four cohorts. Further information about this community sample has been published ( Strobino et al., 2018 ).…”

<p>Precision medicine: retrospective chart review and data analysis of 200 patients on dapsone combination therapy for chronic Lyme disease/post-treatment Lyme disease syndrome: part 1</p>

“…A 2018 publication by Strobino et al61 indicated that for convalescent EM, combinations of the C6 ELISA with a second-tier ELISA or line blot may provide useful alternatives to WB-based testing algorithms, but this needs to be confirmed in larger clinical studies. For those without an EM rash (and not meeting the definition of PTLDS), the two-tiered testing strategy for diagnosing B. burgdorferi misses a large proportion of cases,62 and this approach cannot diagnose new species of Borrelia, including B. miyamotoi and B. burgdorferi sensu lato , which are also known to cause chronic illness 63,64.…”

Recent Progress in Lyme Disease and Remaining Challenges

“…Seroconversion was also rare in samples from the Lyme Disease Biobank, where only 3 of 83 samples (3.6%) from patients with EM > 5 cm seroconverted at the convalescent draw (2-3 months after the acute draw) (23). Other widely known limitations of serological tests are that they are unable to distinguish between a prior exposure to Bb and an active infection, may crossreact with non-Bb antibodies, are subject to variable results depending the selection of antigens used in the first-tier test (31) and some assays, especially the Western immunoblot, require interpretation that may introduce bias (32,33).…”