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

Oct 3, 2026

Lyme disease diagnosis is limited by delayed seroconversion, incomplete immune detection, and persistence of serum antibodies long after infection resolution. In an observational case-control design, a MENSA-based approach was used to measure active humoral responses from circulating antibody-secreting cells. A MicroB-plex Anti-C6/AntipepC10 Immunoassay was developed and validated with CDC sera, then compared in uninfected controls and newly diagnosed patients. Combined serum and MENSA results identified early Lyme patients and showed differing kinetics after treatment.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Abstract

Background

Introduction

Methods

Results

Discussion

Introduction

Clinical context and early diagnosis

Immunological basis

PLOS ONE OPEN ACCESS Citation: Haddad NS, Nozick S, Ohanian S, Smith R, Elias S, Auwaerter PG, et al. (2023) Circulating antibody-secreting cells are a biomarker for early diagnosis in patients with Lyme disease. PLoS ONE 18(11): e0293203 . [https://doi.org/10.1371/journal](https://doi.org/10.1371/journal). pone.0293203 Editor: Ulrike Gertrud Munderloh, University of Minnesota, UNITED STATES Received: April 6, 2023 Accepted: October 7, 2023 Published: November 3, 2023 Copyright: © 2023 Haddad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files. Funding: 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. EunHyung Lee, M. D. The funders had no role in the RESEARCH ARTICLE Circulating antibody-secreting cells are abiomarker for early diagnosis in patients with Lyme disease Natalie S. Haddad1, Sophia Nozick1, Shant Ohanian1, Robert Smith2, Susan Elias2, Paul G. Auwaerter3, F. Eun-Hyung Lee1,4‡, John L. Daiss1 * 1 MicroB-plex, Inc. , Atlanta, GA, United States of America, 2 Division of Infectious Diseases, Maine Medical Center, MaineHealth Institute for Research, Portland, ME, United States of America, 3 Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases, The Johns Hopkins School of Medicine, Baltimore, MD, United States of America, 4 Division of Pulmonary, Allergy & Immunology, Emory University, Atlanta, GA, United States of America ‡ FEHL is co-senior author on this work. * [jdaiss52@gmail.com](jdaiss52@gmail.com) 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/AntipepC10 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 PLOS ONE | [https://doi.org/10.1371/journal.pone.0293203](https://doi.org/10.1371/journal.pone.0293203) November 3, 2023 1 / 17 study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: During the performance of the presented work, Author Natalie S. Haddad was a full-time employee of MicroB-plex, Inc. Sophia Nozick and Shant Ohanian were full-time employees of MicroB-plex, Inc., and generated samples and data reported in this manuscript. Frances Eun-Hyung

FAQs

Why are conventional serological immunoassays insufficient for early Lyme disease diagnosis?

They may miss patients who do not seroconvert, detect antibodies later than symptom onset, and serum antibody levels can remain elevated long after infection resolves.

What is MENSA and what does it measure in this study?

MENSA (Medium Enriched for Newly Synthesized Antibodies) is a diagnostic fluid containing antibodies produced in vitro by circulating antibody-secreting cells, enabling measurement of the active humoral immune response.

How were antibodies against Borrelia antigens detected in serum and MENSA samples?

The MicroB-plex Anti-C6/AntipepC10 Immunoassay measured antibodies specific for C6 and pepC10, using validated serum samples and then applying the assay to uninfected controls and newly diagnosed patients.

Oct 3, 2026

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