Circulating antibody-secreting cells are a biomarker for early diagnosis in patients with Lyme disease

• Type of Material: Article
• Authors: Natalie S. Haddad, MicroB-plex, Inc.; Sophia Nozick, MicroB-plex, Inc.; Shant Ohanian, MicroB-plex, Inc.; Robert Smith, MaineHealth Institute for Research; Susan Elias, MaineHealth Institute for Research; Paul G. Auwaerter, Johns Hopkins University; Frances Eun-Hyung Lee, Emory University; john L. Daiss, MicroB-plex, Inc.
• Language: English
• Date: 2023-11-03
• Publisher: PLOS One
• Publication Version: Final Published Version
• Copyright Statement: © 2023 Haddad et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1371/journal.pone.0293203
• Title of Journal or Parent Work: PLOS
• Volume: 18
• Issue: 11
• Start Page: e0293203
• Grant/Funding Information: The work presented here was supported by the Georgia Research Alliance (GRA) through a GRA Ventures Phase IIA Grant in 2017. The grant was awarded to MicroB-plex, Inc., and titled “Use of Circulating Plasmablasts in the Diagnosis of Early Lyme Disease”; Principal Investigator: F. Eun-Hyung Lee, M.D.
• Keywords: Borrelia burgdorferi; MENSA (Medium Enriched for Newly Synthesized Antibodies); Lyme disease
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

Abstract

Background Diagnostic immunoassays for Lyme disease have several limitations including: 1) not all patients seroconvert; 2) seroconversion occurs later than symptom onset; and 3) serum antibody levels remain elevated long after resolution of the infection. Introduction MENSA (Medium Enriched for Newly Synthesized Antibodies) is a novel diagnostic fluid that contains antibodies produced in vitro by circulating antibody-secreting cells (ASC). It enables measurement of the active humoral immune response. Methods In this observational, case-control study, we developed the MicroB-plex Anti-C6/Anti-pepC10 Immunoassay to measure antibodies specific for the Borrelia burgdorferi peptide antigens C6 and pepC10 and validated it using a CDC serum sample collection. Then we examined serum and MENSA samples from 36 uninfected Control subjects and 12 Newly Diagnosed Lyme Disease Patients. Results Among the CDC samples, antibodies against C6 and/or pepC10 were detected in all seropositive Lyme patients (8/8), but not in sera from seronegative patients or healthy controls (0/24). Serum antibodies against C6 and pepC10 were detected in one of 36 uninfected control subjects (1/36); none were detected in the corresponding MENSA samples (0/36). In samples from newly diagnosed patients, serum antibodies identified 8/12 patients; MENSA antibodies also detected 8/12 patients. The two measures agreed on six positive individuals and differed on four others. In combination, the serum and MENSA tests identified 10/12 early Lyme patients. Typically, serum antibodies persisted 80 days or longer while MENSA antibodies declined to baseline within 40 days of successful treatment. Discussion MENSA-based immunoassays present a promising complement to serum immunoassays for diagnosis and tracking therapeutic success in Lyme infections.