{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T23:57:53Z","timestamp":1770422273345,"version":"3.49.0"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008065","name":"Georgia Research Alliance","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>MENSA (<jats:bold>M<\/jats:bold>edium <jats:bold>E<\/jats:bold>nriched for <jats:bold>N<\/jats:bold>ewly <jats:bold>S<\/jats:bold>ynthesized <jats:bold>A<\/jats:bold>ntibodies) 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>In this observational, case-control study, we developed the MicroB-plex Anti-C6\/Anti-pepC10 Immunoassay to measure antibodies specific for the <jats:italic>Borrelia burgdorferi<\/jats:italic> 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>MENSA-based immunoassays present a promising complement to serum immunoassays for diagnosis and tracking therapeutic success in Lyme infections.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0293203","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T17:31:53Z","timestamp":1699032713000},"page":"e0293203","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Circulating antibody-secreting cells are a biomarker for early diagnosis in patients with Lyme disease"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1348-3094","authenticated-orcid":true,"given":"Natalie S.","family":"Haddad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophia","family":"Nozick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shant","family":"Ohanian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Elias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul G.","family":"Auwaerter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. Eun-Hyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9690-7701","authenticated-orcid":true,"given":"John L.","family":"Daiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,11,3]]},"reference":[{"issue":"4","key":"pone.0293203.ref001","first-page":"515","article-title":"Discovery of the Lyme disease spirochete and its relation to tick vectors.","volume":"57","author":"W. Burgdorfer","year":"1984","journal-title":"Yale J Biol Med."},{"issue":"8","key":"pone.0293203.ref002","first-page":"1935","article-title":"Identifying the vector of Lyme disease.","volume":"69","author":"V Lo Re","year":"2004","journal-title":"Am Fam Physician."},{"issue":"2","key":"pone.0293203.ref003","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1093\/jme\/tjv237","article-title":"County-Scale Distribution of Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae) in the Continental United States.","volume":"53","author":"RJ Eisen","year":"2016","journal-title":"J Med Entomol"},{"key":"pone.0293203.ref004","doi-asserted-by":"crossref","first-page":"16090","DOI":"10.1038\/nrdp.2016.90","article-title":"Lyme borreliosis.","volume":"2","author":"AC Steere","year":"2016","journal-title":"Nat Rev Dis Primers"},{"issue":"2","key":"pone.0293203.ref005","doi-asserted-by":"crossref","DOI":"10.1128\/CMR.00018-19","article-title":"Laboratory Diagnosis of Lyme Borreliosis","volume":"34","author":"JA Branda","year":"2021","journal-title":"Clin Microbiol Rev"},{"issue":"7","key":"pone.0293203.ref006","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1093\/cid\/ciw427","article-title":"Evaluation of the C6 Lyme Enzyme Immunoassay for the Diagnosis of Lyme Disease in Children and Adolescents","volume":"63","author":"SC Lipsett","year":"2016","journal-title":"Clin Infect Dis"},{"issue":"1","key":"pone.0293203.ref007","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/ciaa1215","article-title":"Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.","volume":"72","author":"PM Lantos","year":"2021","journal-title":"Clin Infect Dis"},{"issue":"6","key":"pone.0293203.ref008","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1086\/322669","article-title":"Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10\u201320 years after active Lyme disease","volume":"33","author":"RA Kalish","year":"2001","journal-title":"Clin Infect Dis"},{"issue":"6","key":"pone.0293203.ref009","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.4269\/ajtmh.2006.75.1090","article-title":"Reinfection and relapse in early Lyme disease","volume":"75","author":"PJ Krause","year":"2006","journal-title":"Am J Trop Med Hyg"},{"issue":"20","key":"pone.0293203.ref010","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1056\/NEJMoa1114362","article-title":"Differentiation of reinfection from relapse in recurrent Lyme disease","volume":"367","author":"RB Nadelman","year":"2012","journal-title":"N Engl J Med"},{"issue":"8","key":"pone.0293203.ref011","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1086\/521256","article-title":"Reinfection in patients with Lyme disease","volume":"45","author":"RB Nadelman","year":"2007","journal-title":"Clin Infect Dis"},{"key":"pone.0293203.ref012","doi-asserted-by":"crossref","first-page":"630","DOI":"10.3389\/fimmu.2017.00630","article-title":"The Antibody-Secreting Cell Response to Infection: Kinetics and Clinical Applications.","volume":"8","author":"MJ Carter","year":"2017","journal-title":"Front Immunol"},{"key":"pone.0293203.ref013","first-page":"78","article-title":"Origin and Function of Circulating Plasmablasts during Acute Viral Infections.","volume":"3","author":"K Fink","year":"2012"},{"issue":"9","key":"pone.0293203.ref014","doi-asserted-by":"crossref","first-page":"5514","DOI":"10.4049\/jimmunol.1002932","article-title":"Circulating human antibody-secreting cells during vaccinations and respiratory viral infections are characterized by high specificity and lack of bystander effect","volume":"186","author":"FE Lee","year":"2011","journal-title":"J Immunol"},{"issue":"3","key":"pone.0293203.ref015","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1128\/CMR.18.3.484-509.2005","article-title":"Diagnosis of lyme borreliosis","volume":"18","author":"ME Aguero-Rosenfeld","year":"2005","journal-title":"Clin Microbiol Rev"},{"issue":"6","key":"pone.0293203.ref016","doi-asserted-by":"crossref","first-page":"339","DOI":"10.4049\/immunohorizons.2000024","article-title":"A Bioinformatic Approach to Utilize a Patient\u2019s Antibody-Secreting Cells against Staphylococcus aureus to Detect Challenging Musculoskeletal Infections.","volume":"4","author":"G Muthukrishnan","year":"2020","journal-title":"Immunohorizons."},{"issue":"12","key":"pone.0293203.ref017","article-title":"Tracking Anti-Staphylococcus aureus Antibodies Produced In Vivo and Ex Vivo during Foot Salvage Therapy for Diabetic Foot Infections Reveals Prognostic Insights and Evidence of Diversified Humoral Immunity","volume":"86","author":"I Oh","year":"2018","journal-title":"Infect Immun"},{"key":"pone.0293203.ref018","doi-asserted-by":"crossref","first-page":"112932","DOI":"10.1016\/j.jim.2020.112932","article-title":"Novel immunoassay for diagnosis of ongoing Clostridioides difficile infections using serum and medium enriched for newly synthesized antibodies (MENSA).","volume":"492","author":"NS Haddad","year":"2021","journal-title":"J Immunol Methods"},{"issue":"3","key":"pone.0293203.ref019","doi-asserted-by":"crossref","first-page":"e0220121","DOI":"10.1128\/jcm.02201-21","article-title":"Detection of Newly Secreted Antibodies Predicts Nonrecurrence in Primary Clostridioides difficile Infection","volume":"60","author":"NS Haddad","year":"2022","journal-title":"J Clin Microbiol"},{"issue":"10","key":"pone.0293203.ref020","doi-asserted-by":"crossref","first-page":"3755","DOI":"10.1128\/JCM.01409-14","article-title":"Collection and characterization of samples for establishment of a serum repository for lyme disease diagnostic test development and evaluation","volume":"52","author":"CR Molins","year":"2014","journal-title":"J Clin Microbiol"},{"issue":"1","key":"pone.0293203.ref021","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.5504\/BBEQ.2012.0100","article-title":"C6 Peptides from Borrelia Burgdorferi Sensu Stricto, Borrelia Afzelii and Borrelia Garinii as Antigens for Serological Diagnosis of Lyme Borreliosis.","volume":"27","author":"I Christova","year":"2013","journal-title":"Biotechnology & Biotechnological Equipment."},{"issue":"12","key":"pone.0293203.ref022","doi-asserted-by":"crossref","first-page":"3990","DOI":"10.1128\/JCM.37.12.3990-3996.1999","article-title":"Sensitive and specific serodiagnosis of Lyme disease by enzyme-linked immunosorbent assay with a peptide based on an immunodominant conserved region of Borrelia burgdorferi vlsE","volume":"37","author":"FT Liang","year":"1999","journal-title":"J Clin Microbiol"},{"issue":"8","key":"pone.0293203.ref023","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1086\/374395","article-title":"Serodiagnosis of Lyme disease by kinetic enzyme-linked immunosorbent assay using recombinant VlsE1 or peptide antigens of Borrelia burgdorferi compared with 2-tiered testing using whole-cell lysates","volume":"187","author":"RM Bacon","year":"2003","journal-title":"J Infect Dis"},{"issue":"10","key":"pone.0293203.ref024","doi-asserted-by":"crossref","first-page":"5566","DOI":"10.4049\/jimmunol.163.10.5566","article-title":"An immunodominant conserved region within the variable domain of VlsE, the variable surface antigen of Borrelia burgdorferi","volume":"163","author":"FT Liang","year":"1999","journal-title":"J Immunol"},{"issue":"5","key":"pone.0293203.ref025","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1128\/CVI.00409-10","article-title":"Multiplex immunoassay for Lyme disease using VlsE1-IgG and pepC10-IgM antibodies: improving test performance through bioinformatics","volume":"18","author":"RB Porwancher","year":"2011","journal-title":"Clin Vaccine Immunol"},{"issue":"9","key":"pone.0293203.ref026","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.1073\/pnas.0306845101","article-title":"Outer-surface protein C of the Lyme disease spirochete: a protein induced in ticks for infection of mammals","volume":"101","author":"D Grimm","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0293203.ref027","volume-title":"StatPearls. Treasure Island (FL) ineligible companies","author":"J Shreffler","year":"2023"},{"issue":"11","key":"pone.0293203.ref028","doi-asserted-by":"crossref","first-page":"e0259644","DOI":"10.1371\/journal.pone.0259644","article-title":"Diagnosis of Streptococcus pneumoniae infection using circulating antibody secreting cells.","volume":"16","author":"S Kyu","year":"2021","journal-title":"PLoS One."},{"issue":"4","key":"pone.0293203.ref029","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1128\/CVI.00685-15","article-title":"Five-Antigen Fluorescent Bead-Based Assay for Diagnosis of Lyme Disease.","volume":"23","author":"ME Embers","year":"2016","journal-title":"Clin Vaccine Immunol"},{"issue":"11","key":"pone.0293203.ref030","doi-asserted-by":"crossref","first-page":"e0134421","DOI":"10.1128\/JCM.01344-21","article-title":"Serologic Response to Borrelia Antigens Varies with Clinical Phenotype in Children and Young Adults with Lyme Disease","volume":"59","author":"FA Radtke","year":"2021","journal-title":"J Clin Microbiol"},{"issue":"2","key":"pone.0293203.ref031","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/BF00328982","article-title":"Immunodominant proteins of Borrelia burgdorferi, the etiological agent of lyme borreliosis","volume":"7","author":"B Wilske","year":"1991","journal-title":"World J Microbiol Biotechnol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0293203","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T17:32:12Z","timestamp":1699032732000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0293203"}},"subtitle":[],"editor":[{"given":"Ulrike Gertrud","family":"Munderloh","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,11,3]]},"references-count":31,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0293203","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,3]]}}}