The potential to improve Lyme disease diagnostics through quantification of immunoglobulin class switching patterns.

N. Nair, A. Marques , E. J. Horn, G. Brown et al., J Clin Microbiol 63:e0034725, 2025, https://doi.org/10.1128/jcm.00347-25 present data to demonstrate that infection by Borrelia burgdorferi, the primary causative agent of Lyme disease in the USA, leads to immunoglobulin class switching in antibodies specifically against the immunodominant antigen, VlsE (variable major protein-like sequence, expressed), in a predictable pattern between the early acute (<1 month illness duration) to late-stage Lyme arthritis stages. Detection of anti-VlsE isotypes in sera was highly specific to Lyme disease patients, and the frequencies and abundances of IgM, IgG, and IgA isotypes progressed in a pattern consistent with the development of an anti-B. burgdorferi antibody response. Applying multivariate and machine learning modeling methods, they found the profile of isotypes quantified performed particularly well at correctly classifying early acute sera samples. They also identified IgG4 as a potential biomarker unique to Lyme arthritis patients. Overall, the findings suggest that improvements in Lyme disease diagnostics may be attained by quantifying specific antibody isotypes against B. burgdorferi antigens.