{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T15:10:39Z","timestamp":1783177839827,"version":"3.54.6"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["RO1AI132680"],"award-info":[{"award-number":["RO1AI132680"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-008079"],"award-info":[{"award-number":["INV-008079"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Lipoarabinomannan (LAM), a component of the\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (MTB) cell wall, is detectable in the urine of MTB infected patients with active tuberculosis (TB). LAM-specific antibodies (Igs) have been developed by a variety of traditional and recombinant methods for potential use in a rapid diagnostic test (RDT). We evaluated the analytical performance of the TB LAM Igs to identify pairs that offer superior performance over existing urine LAM tests. We assessed 25 new and 4 existing Igs in a matrixed format using a multiplex electrochemiluminescence-based liquid immunoassay. A total of 841 paired Ig combinations were challenged with\n                    <jats:italic>in vitro<\/jats:italic>\n                    cultured LAM (cLAM) derived from MTB strains representing diverse phylogenetic lineages, alongside urinary LAM (uLAM) from the urine of adults with active pulmonary TB. Analytical sensitivity of down-selected Ig pairs was determined using MTB Aoyama-B cLAM, while diagnostic accuracy was determined using clinical samples. When testing cLAM, the reactivity of Ig pairs was similar across MTB lineages 1\u20134 but lineage 5:6 had significantly more reactivity among Ig pairs. Overall, 41 Ig pairs had a strong binding affinity to cLAM, as compared to the reference pair of S4-20\/A194-01, and 28 Ig pairs therein exhibited a strong affinity for both cLAM and uLAM. Retrospective testing on clinical urine specimens demonstrated varying sensitivities (12\u201380%) and specificities (14\u2013100%). The five top pairs had a similar analytical limit of detection to the reference pair but in four instances, the sensitivity and specificity with clinical uLAM samples was poor. Overall, epitopes presented by uLAM are different from cLAM, which may affect antibody performance when testing uLAM in patient samples. Several new Ig pairs had similar ranges of high sensitivity to cLAM but overall, there were no new candidate Ig pairs identified in this round of screening with increased performance with uLAM as compared to an existing optimal pair.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0274415","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T13:52:00Z","timestamp":1664545920000},"page":"e0274415","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Performance of novel antibodies for lipoarabinomannan to develop diagnostic tests for Mycobacterium tuberculosis"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7665-5458","authenticated-orcid":true,"given":"Jason L.","family":"Cantera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine 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K.","family":"Drain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Andama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham","family":"Pinter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Kawasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunilla","family":"K\u00e4llenius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6138-690X","authenticated-orcid":true,"given":"Christopher","family":"Sundling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen M.","family":"Dobos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danara","family":"Flores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5215-4699","authenticated-orcid":true,"given":"Delphi","family":"Chatterjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia R.","family":"Halas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4019-9037","authenticated-orcid":true,"given":"David S.","family":"Boyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"pone.0274415.ref001","first-page":"57","author":"World Health Organization","year":"2021","journal-title":"Global Tuberculosis Report"},{"key":"pone.0274415.ref002","doi-asserted-by":"crossref","first-page":"e907","DOI":"10.1016\/S2214-109X(16)30248-0","article-title":"Location, location, location: tuberculosis services in highest burden countries","volume":"4","author":"S Huddart","year":"2016","journal-title":"Lancet Glob Health"},{"key":"pone.0274415.ref003","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/S1473-3099(03)00609-1","article-title":"Clinical diagnosis of smear-negative pulmonary tuberculosis in low-income countries: the current evidence","volume":"3","author":"K Siddiqi","year":"2003","journal-title":"Lancet Infect 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[cited 11 Aug 2021]. 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Hamasur","year":"2019","journal-title":"Poster. 50th Union World Conference on Lung Health"},{"key":"pone.0274415.ref028","doi-asserted-by":"crossref","first-page":"18012","DOI":"10.1038\/s41598-019-54537-9","article-title":"Improved Alere Determine Lipoarabinomannan Antigen Detection Test for the Diagnosis of Human and Bovine Tuberculosis by Manipulating Urine and Milk.","volume":"9","author":"JI Garc\u00eda","year":"2019","journal-title":"Sci Rep"},{"key":"pone.0274415.ref029","doi-asserted-by":"crossref","first-page":"e0257615","DOI":"10.1371\/journal.pone.0257615","article-title":"Immobilization of Proteinase K for urine pretreatment to improve diagnostic accuracy of active tuberculosis","volume":"16","author":"Y Panraksa","year":"2021","journal-title":"PLoS One"},{"key":"pone.0274415.ref030","article-title":"Automated liquid handling robot for rapid lateral flow assay development","author":"CE Anderson","year":"2022","journal-title":"Anal Bioanal 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Organization","year":"2015"},{"key":"pone.0274415.ref040","first-page":"28","article-title":"Lateral flow urine lipoarabinomannan assay (LF-LAM) for the diagnosis of active tuberculosis in people living with HIV","author":"World Health Organization","year":"2019"},{"key":"pone.0274415.ref041","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.tube.2018.06.004","article-title":"Detection of lipoarabinomannan in urine and serum of HIV-positive and HIV-negative TB suspects using an improved capture-enzyme linked immuno absorbent assay and gas chromatography\/mass spectrometry","volume":"111","author":"AG Amin","year":"2018","journal-title":"Tuberculosis (Edinb)."},{"key":"pone.0274415.ref042","doi-asserted-by":"crossref","first-page":"13944","DOI":"10.1038\/s41598-020-70669-9","article-title":"Lipoarabinomannan antigenic epitope differences in tuberculosis disease subtypes","volume":"10","author":"R Magni","year":"2020","journal-title":"Sci 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