Abstract

Lyme disease is commonly diagnosed by serologic response to Borrelia burgdorferi and related species, but the relationship between serologic targets and clinical features is unknown. We developed a multi-antigen Luminex-based panel and evaluated IgG responses in 527 children 1 to 21 years of age assessed for Lyme disease across 4 Pedi Lyme Net emergency departments, including 127 Lyme cases defined by either an erythema migrans (EM) lesion or positive C6 enzyme immunoassay followed by immunoblot and 400 patients considered clinical mimics. Of 42 antigens tested, 26 elicited specific reactivity in Lyme patients, without marked age-dependent variation. Children with single EM lesions typically lacked Borrelia-specific IgG. By principal component analysis, children with early disseminated and late Lyme disease clustered separately from clinical mimics and also from each other. Neurological disease and arthritis exhibited distinct serologic responses, with OspC variants overrepresented in neurological disease and p100, BmpA, p58 and p45 overrepresented in arthritis. Machine learning identified a 3-antigen panel (VlsE_Bb, p41_Bb, OspC_Bafz) that distinguished Lyme disease from clinical mimics with a sensitivity of 86.6% (95% confidence interval [CI] 80.3-92.1) and a specificity of 95.5% (95% CI 93.4-97.4). Sensitivity was much lower in early Lyme disease (38.5%, 95% CI 15.4-69.2). Interestingly, 17 children classified as Lyme mimics had a positive 3-antigen panel, suggesting that more comprehensive serologic analysis could help refine Lyme diagnosis. In conclusion, multiplex antigen panels provide a novel approach to understanding the immune response in Lyme disease, potentially helping to facilitate accurate diagnosis and to understand differences between clinical stages.

View details for DOI 10.1128/JCM.01344-21

View details for PubMedID 34379528