{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:09:39Z","timestamp":1785409779887,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,1]]},"group-title":"Immunology","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["INV-004048),"],"award-info":[{"award-number":["INV-004048),"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01-AI152157"],"award-info":[{"award-number":["R01-AI152157"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R56-AI171023"],"award-info":[{"award-number":["R56-AI171023"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001774","name":"New Jersey Health Foundation","doi-asserted-by":"crossref","award":["PC 92-20"],"award-info":[{"award-number":["PC 92-20"]}],"id":[{"id":"10.13039\/100001774","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Lipoarabinomannan (LAM) is a useful biomarker for detection of\n                  <jats:italic>M. tuberculosis<\/jats:italic>\n                  infection and disease. Related antigens can be detected in urine samples of TB patients by combinations of monoclonal antibodies (mAbs) directed against specific epitopes expressed in LAM. While sensitive for samples from patients with active TB disease who have HIV-1 co-infections, these assays are less effective for other populations, and there is therefore a need for more sensitive antibodies that can improve the sensitivity of these assays. Here we characterize the antigen and epitope specificities, sequence diversity and isotype dependencies of eight LAM-specific human mAbs that target five distinct arabinose- and mannose-dependent epitopes present in LAM and lipoarabinomannan (LM). Whereas all of the mAbs recognized ManLAM, only a few, including A194-01, consistently detected antigens in TB+ urine samples. Converting A194-01 from the IgG1 to the IgM isotype resulted in broader recognition of poly-Ara glycan epitopes, and increased sensitivity for clinical antigens when combined with several capture reagents, including RU95-C1, a novel antibody targeting the mannan domain of LAM. These results define novel epitopes that are differentially expressed in bacterial and urinary forms of LAM, and identify novel antibody combinations which possess enhanced diagnostic utility for clinical forms of LAM.\n                <\/jats:p>","DOI":"10.64898\/2026.06.28.735056","type":"posted-content","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T18:30:21Z","timestamp":1782930621000},"source":"Crossref","is-referenced-by-count":0,"title":["Novel human monoclonal antibodies with enhanced sensitivity for lipoarabinomannan antigens present in urines of TB patients"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2933-9812","authenticated-orcid":false,"given":"Alok","family":"Choudhary","sequence":"first","affiliation":[{"name":"Rutgers Health, New Jersey Medical School, N.J., USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4483-638X","authenticated-orcid":false,"given":"Deendayal","family":"Patel","sequence":"additional","affiliation":[{"name":"Rutgers Health, New Jersey Medical School, N.J., USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3320-2162","authenticated-orcid":false,"given":"William J.","family":"Honnen","sequence":"additional","affiliation":[{"name":"Rutgers Health, New Jersey Medical School, N.J., USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4840-1685","authenticated-orcid":false,"given":"Afsal","family":"Kolloli","sequence":"additional","affiliation":[{"name":"Rutgers Health, New Jersey Medical School, N.J., USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3465-3774","authenticated-orcid":false,"given":"Charles","family":"Reichman","sequence":"additional","affiliation":[{"name":"Rutgers Health, New Jersey Medical School, N.J., USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamaljit","family":"Kaur","sequence":"additional","affiliation":[{"name":"Rutgers Health, New Jersey Medical School, N.J., USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8200-6534","authenticated-orcid":false,"given":"Ruixiang Blake","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Univeristy of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6161-6720","authenticated-orcid":false,"given":"Elizabeth","family":"Nakabugo","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasinghe","family":"Emmanuel","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7263-3198","authenticated-orcid":false,"given":"Lydia","family":"Nakiyingi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8331-8211","authenticated-orcid":false,"given":"Todd","family":"Lowary","sequence":"additional","affiliation":[{"name":"Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan"},{"name":"Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3262-3304","authenticated-orcid":false,"given":"Abraham","family":"Pinter","sequence":"additional","affiliation":[{"name":"Rutgers Health, New Jersey Medical School, N.J., USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026073003300558000_2026.06.28.735056v2.1","unstructured":"WHO. Meeting Report: Target product profiles for tuberculosis diagnosis and detection of drug resistance. Geneva: World Health Organization; 2024. . World Health Organization Press. 2024;Licence: CC BY-NC-SA 3.0 IGO"},{"key":"2026073003300558000_2026.06.28.735056v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70251-1"},{"key":"2026073003300558000_2026.06.28.735056v2.3","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3283553685"},{"key":"2026073003300558000_2026.06.28.735056v2.4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103285"},{"key":"2026073003300558000_2026.06.28.735056v2.5","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-016-1837-z"},{"key":"2026073003300558000_2026.06.28.735056v2.6","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-016-0603-9"},{"key":"2026073003300558000_2026.06.28.735056v2.7","unstructured":"WHO. The Use of Lateral Flow Urine Lipoarabinomannan Assay (LF-LAM) for the Diagnosis and Screening of Active Tuberculosis in People Living with HIV:. Vol. http:\/\/www.who.int\/tb\/publications\/use-of-lf-lam-tb-hiv\/en\/. 2015. Policy Update: World Health Organization ."},{"key":"2026073003300558000_2026.06.28.735056v2.8","unstructured":"WHO. Lateral flow urine lipoarabinomannan assay (LF-LAM) for the diagnosis of active tuberculosis in people living with HIV. Policy update. Geneva: World Health Organization; 2019 Licence: CC BY-NC-SA 30 IGO. 2019;"},{"key":"2026073003300558000_2026.06.28.735056v2.9","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701673"},{"key":"2026073003300558000_2026.06.28.735056v2.10","doi-asserted-by":"crossref","unstructured":"Sigal GB , Pinter A , Lowary TL , et al. A novel sensitive immunoassay targeting the MTX-Lipoarabinomannan epitope meets the WHO\u2019s performance target for Tuberculosis diagnosis. Journal of Clinical Microbiology, In press. Journal of Clinical Microbiology. 2018;December 2018 Volume 56 Issue (12):e01338-18.","DOI":"10.1128\/JCM.01338-18"},{"key":"2026073003300558000_2026.06.28.735056v2.11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0215443"},{"key":"2026073003300558000_2026.06.28.735056v2.12","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.4c00079"},{"key":"2026073003300558000_2026.06.28.735056v2.13","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30001-5"},{"key":"2026073003300558000_2026.06.28.735056v2.14","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz530"},{"key":"2026073003300558000_2026.06.28.735056v2.15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI140461"},{"key":"2026073003300558000_2026.06.28.735056v2.16","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(22)00463-6"},{"key":"2026073003300558000_2026.06.28.735056v2.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2022.115879"},{"key":"2026073003300558000_2026.06.28.735056v2.18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0274415"},{"key":"2026073003300558000_2026.06.28.735056v2.19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0297828"},{"issue":"11","key":"2026073003300558000_2026.06.28.735056v2.20","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.1128\/iai.55.11.2860-2863.1987","article-title":"Most Mycobacterium leprae carbohydrate-reactive monoclonal antibodies are directed to lipoarabinomannan","volume":"55","year":"1987","journal-title":"Infect Immun"},{"issue":"9","key":"2026073003300558000_2026.06.28.735056v2.21","first-page":"6234","article-title":"Lipoarabinomannan of Mycobacterium tuberculosis","volume":"267","year":"1992","journal-title":"Capping with mannosyl residues in some strains. J Biol Chem"},{"key":"2026073003300558000_2026.06.28.735056v2.22","doi-asserted-by":"publisher","DOI":"10.1038\/srep10281"},{"key":"2026073003300558000_2026.06.28.735056v2.23","unstructured":"Macary PA , Chan CEZ , Hanson BJ , Wenk MR , inventors; Pathogenic mycobacteria-derived mannose-capped lipoarabinomannan antigen binding proteins U.S. 2013."},{"key":"2026073003300558000_2026.06.28.735056v2.24","unstructured":"Katsuragi K , Togashi M , Oda T , et al , inventors; Otsuka Pharmaceutical Co Ltd, assignee. Anti-lipoarabinomannan antibody and immunoassay for mycobacteriosis using said antibody. patent application EP2821415A1. 2013."},{"key":"2026073003300558000_2026.06.28.735056v2.25","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606330"},{"key":"2026073003300558000_2026.06.28.735056v2.26","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02714-w"},{"key":"2026073003300558000_2026.06.28.735056v2.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2022.07.001"},{"key":"2026073003300558000_2026.06.28.735056v2.28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41431-2"},{"key":"2026073003300558000_2026.06.28.735056v2.29","doi-asserted-by":"publisher","DOI":"10.1081\/CAR-120025322"},{"key":"2026073003300558000_2026.06.28.735056v2.30","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.7b00797"},{"issue":"17","key":"2026073003300558000_2026.06.28.735056v2.31","doi-asserted-by":"crossref","first-page":"12401","DOI":"10.1016\/S0021-9258(18)31404-2","article-title":"Structural features of lipoarabinomannan from Mycobacterium bovis BCG. Determination of molecular mass by laser desorption mass spectrometry","volume":"268","year":"1993","journal-title":"J Biol Chem"},{"key":"2026073003300558000_2026.06.28.735056v2.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jasms.2005.02.023"},{"key":"2026073003300558000_2026.06.28.735056v2.33","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.5317"},{"key":"2026073003300558000_2026.06.28.735056v2.34","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200454119"},{"key":"2026073003300558000_2026.06.28.735056v2.35","doi-asserted-by":"publisher","DOI":"10.1021\/ja057373q"},{"key":"2026073003300558000_2026.06.28.735056v2.36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.599415"},{"key":"2026073003300558000_2026.06.28.735056v2.37","doi-asserted-by":"publisher","DOI":"10.1038\/s42004-020-00356-3"},{"issue":"16","key":"2026073003300558000_2026.06.28.735056v2.38","doi-asserted-by":"crossref","first-page":"9272","DOI":"10.1016\/S0021-9258(19)38843-X","article-title":"Evidence for the presence of a phosphatidylinositol anchor on the lipoarabinomannan and lipomannan of Mycobacterium tuberculosis","volume":"265","year":"1990","journal-title":"J Biol Chem"},{"key":"2026073003300558000_2026.06.28.735056v2.39","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12175"},{"key":"2026073003300558000_2026.06.28.735056v2.40","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.4.2014"},{"key":"2026073003300558000_2026.06.28.735056v2.41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1112660108"},{"key":"2026073003300558000_2026.06.28.735056v2.42","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2067-2074.2004"},{"key":"2026073003300558000_2026.06.28.735056v2.43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04183.x"},{"key":"2026073003300558000_2026.06.28.735056v2.44","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics15030291"},{"key":"2026073003300558000_2026.06.28.735056v2.45","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702690200"},{"key":"2026073003300558000_2026.06.28.735056v2.46","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119433"},{"key":"2026073003300558000_2026.06.28.735056v2.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108065"},{"key":"2026073003300558000_2026.06.28.735056v2.48","doi-asserted-by":"publisher","DOI":"10.1006\/bcmd.1996.0020"},{"key":"2026073003300558000_2026.06.28.735056v2.49","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160201"},{"key":"2026073003300558000_2026.06.28.735056v2.50","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0879-y"},{"key":"2026073003300558000_2026.06.28.735056v2.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109604"},{"key":"2026073003300558000_2026.06.28.735056v2.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.05.008"},{"key":"2026073003300558000_2026.06.28.735056v2.53","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1406974111"},{"key":"2026073003300558000_2026.06.28.735056v2.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.06.026"},{"key":"2026073003300558000_2026.06.28.735056v2.55","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msab120"},{"key":"2026073003300558000_2026.06.28.735056v2.56","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msy096"},{"key":"2026073003300558000_2026.06.28.735056v2.57","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a040454"},{"key":"2026073003300558000_2026.06.28.735056v2.58","doi-asserted-by":"publisher","DOI":"10.2307\/2408678"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.06.28.735056","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:30:17Z","timestamp":1785407417000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.06.28.735056"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":58,"URL":"https:\/\/doi.org\/10.64898\/2026.06.28.735056","relation":{},"subject":[],"published":{"date-parts":[[2026,7,1]]},"subtype":"preprint"}}