New synthetic lipid antigens for rapid serological diagnosis of tuberculosis
During pulmonary tuberculosis (PTB) antibodies are generated to trehalose esters of mycolic acids which are cell wall lipids of Mycobacterium tuberculosis (Mtb). Attempts have been made to use these complex natural mixtures in serological tests for PTB diagnosis. The aim of this work was to determin...
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| creator | Jones, Alison Pitts, Mark Al Dulayymi, Juma'a R Gibbons, James Ramsay, Andrew Goletti, Delia Gwenin, Christopher D Baird, Mark S |
| description | During pulmonary tuberculosis (PTB) antibodies are generated to trehalose esters of mycolic acids which are cell wall lipids of Mycobacterium tuberculosis (Mtb). Attempts have been made to use these complex natural mixtures in serological tests for PTB diagnosis.
The aim of this work was to determine whether a serological test based on a panel of defined individual trehalose esters of characteristic synthetic mycolic acids has improved diagnostic accuracy in distinguishing patients with culture positive PTB from individuals who were Mtb culture negative.
One hundred serum samples from well-characterized patients with presumptive tuberculosis, and diagnosed as having pulmonary smear and culture positive TB, or being culture and smear negative were evaluated by ELISA using different combinations of synthetic antigens and secondary antibodies. Using cut-off values determined from these samples, we validated this study blind in samples from a further 249 presumptive TB patients.
With the first 100 samples, detailed responses depended both on the precise structure of the antigen and on the secondary antibody. Using a single antigen, a sensitivity/specificity combination for smear and culture positive PTB detection of 85 and 88% respectively was achieved; this increased to 96% and 95% respectively by a statistical combination of the results with seven antigens. In the blind study a sensitivity/specificity of 87% and 83% was reached with a single antigen. With some synthetic antigens, the responses from all 349 samples were significantly better than those with the natural mixture. Combining the results for seven antigens allowed a distinction between culture positive and negative with a ROC AUC of 0.95.
We have identified promising antigen candidates for serological assays that could be used to diagnose PTB and which could be the basis of a much-needed, simple, rapid diagnostic test that would bring care closer to communities. |
| doi_str_mv | 10.1371/journal.pone.0181414 |
| format | Article |
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The aim of this work was to determine whether a serological test based on a panel of defined individual trehalose esters of characteristic synthetic mycolic acids has improved diagnostic accuracy in distinguishing patients with culture positive PTB from individuals who were Mtb culture negative.
One hundred serum samples from well-characterized patients with presumptive tuberculosis, and diagnosed as having pulmonary smear and culture positive TB, or being culture and smear negative were evaluated by ELISA using different combinations of synthetic antigens and secondary antibodies. Using cut-off values determined from these samples, we validated this study blind in samples from a further 249 presumptive TB patients.
With the first 100 samples, detailed responses depended both on the precise structure of the antigen and on the secondary antibody. Using a single antigen, a sensitivity/specificity combination for smear and culture positive PTB detection of 85 and 88% respectively was achieved; this increased to 96% and 95% respectively by a statistical combination of the results with seven antigens. In the blind study a sensitivity/specificity of 87% and 83% was reached with a single antigen. With some synthetic antigens, the responses from all 349 samples were significantly better than those with the natural mixture. Combining the results for seven antigens allowed a distinction between culture positive and negative with a ROC AUC of 0.95.
We have identified promising antigen candidates for serological assays that could be used to diagnose PTB and which could be the basis of a much-needed, simple, rapid diagnostic test that would bring care closer to communities.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0181414</identifier><identifier>PMID: 28806423</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Adult ; Algorithms ; Antibodies ; Antigens ; Antigens, Bacterial - chemistry ; Antigens, Bacterial - metabolism ; Biology and Life Sciences ; Cell culture ; Cell walls ; Demography ; Diagnosis ; Diagnostic systems ; Disease ; Enzyme-Linked Immunosorbent Assay ; Esters ; Female ; Health aspects ; Humans ; Immunoglobulins ; Immunology ; Infections ; Lipids ; Male ; Medical diagnosis ; Medicine and Health Sciences ; Methods ; Middle Aged ; Mycolic acids ; Mycolic Acids - chemistry ; Patients ; Physical Sciences ; Predictive Value of Tests ; Research and Analysis Methods ; Sensitivity ; Serologic Tests - methods ; Serological tests ; Smear ; Statistical analysis ; Statistical methods ; Trehalose ; Tuberculosis ; Tuberculosis, Pulmonary - blood ; Tuberculosis, Pulmonary - diagnosis ; Tuberculosis, Pulmonary - microbiology ; Young Adult</subject><ispartof>PloS one, 2017-08, Vol.12 (8), p.e0181414-e0181414</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Jones et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Jones et al 2017 Jones et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-b89ba5465656dd3b20cd7a784a412ec5047ec23a9a18e252d8e760f169394ffc3</citedby><cites>FETCH-LOGICAL-c692t-b89ba5465656dd3b20cd7a784a412ec5047ec23a9a18e252d8e760f169394ffc3</cites><orcidid>0000-0001-5340-8745</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555574/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555574/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28806423$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>García-García, José-María</contributor><creatorcontrib>Jones, Alison</creatorcontrib><creatorcontrib>Pitts, Mark</creatorcontrib><creatorcontrib>Al Dulayymi, Juma'a R</creatorcontrib><creatorcontrib>Gibbons, James</creatorcontrib><creatorcontrib>Ramsay, Andrew</creatorcontrib><creatorcontrib>Goletti, Delia</creatorcontrib><creatorcontrib>Gwenin, Christopher D</creatorcontrib><creatorcontrib>Baird, Mark S</creatorcontrib><title>New synthetic lipid antigens for rapid serological diagnosis of tuberculosis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>During pulmonary tuberculosis (PTB) antibodies are generated to trehalose esters of mycolic acids which are cell wall lipids of Mycobacterium tuberculosis (Mtb). Attempts have been made to use these complex natural mixtures in serological tests for PTB diagnosis.
The aim of this work was to determine whether a serological test based on a panel of defined individual trehalose esters of characteristic synthetic mycolic acids has improved diagnostic accuracy in distinguishing patients with culture positive PTB from individuals who were Mtb culture negative.
One hundred serum samples from well-characterized patients with presumptive tuberculosis, and diagnosed as having pulmonary smear and culture positive TB, or being culture and smear negative were evaluated by ELISA using different combinations of synthetic antigens and secondary antibodies. Using cut-off values determined from these samples, we validated this study blind in samples from a further 249 presumptive TB patients.
With the first 100 samples, detailed responses depended both on the precise structure of the antigen and on the secondary antibody. Using a single antigen, a sensitivity/specificity combination for smear and culture positive PTB detection of 85 and 88% respectively was achieved; this increased to 96% and 95% respectively by a statistical combination of the results with seven antigens. In the blind study a sensitivity/specificity of 87% and 83% was reached with a single antigen. With some synthetic antigens, the responses from all 349 samples were significantly better than those with the natural mixture. Combining the results for seven antigens allowed a distinction between culture positive and negative with a ROC AUC of 0.95.
We have identified promising antigen candidates for serological assays that could be used to diagnose PTB and which could be the basis of a much-needed, simple, rapid diagnostic test that would bring care closer to communities.</description><subject>Acids</subject><subject>Adult</subject><subject>Algorithms</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Antigens, Bacterial - chemistry</subject><subject>Antigens, Bacterial - metabolism</subject><subject>Biology and Life Sciences</subject><subject>Cell culture</subject><subject>Cell walls</subject><subject>Demography</subject><subject>Diagnosis</subject><subject>Diagnostic systems</subject><subject>Disease</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Esters</subject><subject>Female</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Immunology</subject><subject>Infections</subject><subject>Lipids</subject><subject>Male</subject><subject>Medical diagnosis</subject><subject>Medicine and Health Sciences</subject><subject>Methods</subject><subject>Middle Aged</subject><subject>Mycolic acids</subject><subject>Mycolic Acids - chemistry</subject><subject>Patients</subject><subject>Physical Sciences</subject><subject>Predictive Value of Tests</subject><subject>Research and Analysis Methods</subject><subject>Sensitivity</subject><subject>Serologic Tests - methods</subject><subject>Serological tests</subject><subject>Smear</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Trehalose</subject><subject>Tuberculosis</subject><subject>Tuberculosis, Pulmonary - blood</subject><subject>Tuberculosis, Pulmonary - diagnosis</subject><subject>Tuberculosis, Pulmonary - microbiology</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkttu1DAQhiMEoqXwBggiISG42MXHxL5BqioOK62oxOnWcnzIuvLGWzsB-vY4u2m1Qb0gvogz-eYfz_gviucQLCGu4burMMRO-uUudGYJIIMEkgfFKeQYLSoE8MOj_UnxJKUrAChmVfW4OEGMgYogfFqsv5jfZbrp-o3pnSq92zldyq53relSaUMsoxxDycTgQ-uU9KV2su1CcqkMtuyHxkQ1-PH7afHISp_Ms-l9Vvz4-OH7xefF-vLT6uJ8vVAVR_2iYbyRlFQ0L61xg4DStawZkQQioyggtVEISy4hM4gizUxdAQsrjjmxVuGz4uVBd5fLimkQSUCOWE05rEkmVgdCB3kldtFtZbwRQTqxD4TYChlzw96IxhLbNEopyhmhDeFQWw2o5hZjqq3NWu-nakOzNVqZro_Sz0Tnfzq3EW34Jej47A_zZhKI4XowqRdbl5TxXnYmDPtzcwgorGFGX_2D3t_dRLUyN-A6G3JdNYqKc5pvuSaUjdTyHiovbbZOZddYl-OzhLezhMz05k_fyiElsfr29f_Zy59z9vURuzHS95sU_NC70KU5SA6giiGlaOzdkCEQo-lvpyFG04vJ9DntxfEF3SXduhz_BSnc_Po</recordid><startdate>20170814</startdate><enddate>20170814</enddate><creator>Jones, Alison</creator><creator>Pitts, Mark</creator><creator>Al Dulayymi, Juma'a R</creator><creator>Gibbons, James</creator><creator>Ramsay, Andrew</creator><creator>Goletti, Delia</creator><creator>Gwenin, Christopher D</creator><creator>Baird, Mark S</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5340-8745</orcidid></search><sort><creationdate>20170814</creationdate><title>New synthetic lipid antigens for rapid serological diagnosis of tuberculosis</title><author>Jones, Alison ; Pitts, Mark ; Al Dulayymi, Juma'a R ; Gibbons, James ; Ramsay, Andrew ; Goletti, Delia ; Gwenin, Christopher D ; Baird, Mark S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-b89ba5465656dd3b20cd7a784a412ec5047ec23a9a18e252d8e760f169394ffc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acids</topic><topic>Adult</topic><topic>Algorithms</topic><topic>Antibodies</topic><topic>Antigens</topic><topic>Antigens, Bacterial - chemistry</topic><topic>Antigens, Bacterial - metabolism</topic><topic>Biology and Life Sciences</topic><topic>Cell culture</topic><topic>Cell walls</topic><topic>Demography</topic><topic>Diagnosis</topic><topic>Diagnostic systems</topic><topic>Disease</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Esters</topic><topic>Female</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>Immunology</topic><topic>Infections</topic><topic>Lipids</topic><topic>Male</topic><topic>Medical diagnosis</topic><topic>Medicine and Health Sciences</topic><topic>Methods</topic><topic>Middle Aged</topic><topic>Mycolic acids</topic><topic>Mycolic Acids - chemistry</topic><topic>Patients</topic><topic>Physical Sciences</topic><topic>Predictive Value of Tests</topic><topic>Research and Analysis Methods</topic><topic>Sensitivity</topic><topic>Serologic Tests - methods</topic><topic>Serological tests</topic><topic>Smear</topic><topic>Statistical analysis</topic><topic>Statistical methods</topic><topic>Trehalose</topic><topic>Tuberculosis</topic><topic>Tuberculosis, Pulmonary - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jones, Alison</au><au>Pitts, Mark</au><au>Al Dulayymi, Juma'a R</au><au>Gibbons, James</au><au>Ramsay, Andrew</au><au>Goletti, Delia</au><au>Gwenin, Christopher D</au><au>Baird, Mark S</au><au>García-García, José-María</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New synthetic lipid antigens for rapid serological diagnosis of tuberculosis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-08-14</date><risdate>2017</risdate><volume>12</volume><issue>8</issue><spage>e0181414</spage><epage>e0181414</epage><pages>e0181414-e0181414</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>During pulmonary tuberculosis (PTB) antibodies are generated to trehalose esters of mycolic acids which are cell wall lipids of Mycobacterium tuberculosis (Mtb). Attempts have been made to use these complex natural mixtures in serological tests for PTB diagnosis.
The aim of this work was to determine whether a serological test based on a panel of defined individual trehalose esters of characteristic synthetic mycolic acids has improved diagnostic accuracy in distinguishing patients with culture positive PTB from individuals who were Mtb culture negative.
One hundred serum samples from well-characterized patients with presumptive tuberculosis, and diagnosed as having pulmonary smear and culture positive TB, or being culture and smear negative were evaluated by ELISA using different combinations of synthetic antigens and secondary antibodies. Using cut-off values determined from these samples, we validated this study blind in samples from a further 249 presumptive TB patients.
With the first 100 samples, detailed responses depended both on the precise structure of the antigen and on the secondary antibody. Using a single antigen, a sensitivity/specificity combination for smear and culture positive PTB detection of 85 and 88% respectively was achieved; this increased to 96% and 95% respectively by a statistical combination of the results with seven antigens. In the blind study a sensitivity/specificity of 87% and 83% was reached with a single antigen. With some synthetic antigens, the responses from all 349 samples were significantly better than those with the natural mixture. Combining the results for seven antigens allowed a distinction between culture positive and negative with a ROC AUC of 0.95.
We have identified promising antigen candidates for serological assays that could be used to diagnose PTB and which could be the basis of a much-needed, simple, rapid diagnostic test that would bring care closer to communities.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28806423</pmid><doi>10.1371/journal.pone.0181414</doi><tpages>e0181414</tpages><orcidid>https://orcid.org/0000-0001-5340-8745</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2017-08, Vol.12 (8), p.e0181414-e0181414 |
| issn | 1932-6203 1932-6203 |
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| recordid | cdi_plos_journals_1928759174 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acids Adult Algorithms Antibodies Antigens Antigens, Bacterial - chemistry Antigens, Bacterial - metabolism Biology and Life Sciences Cell culture Cell walls Demography Diagnosis Diagnostic systems Disease Enzyme-Linked Immunosorbent Assay Esters Female Health aspects Humans Immunoglobulins Immunology Infections Lipids Male Medical diagnosis Medicine and Health Sciences Methods Middle Aged Mycolic acids Mycolic Acids - chemistry Patients Physical Sciences Predictive Value of Tests Research and Analysis Methods Sensitivity Serologic Tests - methods Serological tests Smear Statistical analysis Statistical methods Trehalose Tuberculosis Tuberculosis, Pulmonary - blood Tuberculosis, Pulmonary - diagnosis Tuberculosis, Pulmonary - microbiology Young Adult |
| title | New synthetic lipid antigens for rapid serological diagnosis of tuberculosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T21%3A52%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=New%20synthetic%20lipid%20antigens%20for%20rapid%20serological%20diagnosis%20of%20tuberculosis&rft.jtitle=PloS%20one&rft.au=Jones,%20Alison&rft.date=2017-08-14&rft.volume=12&rft.issue=8&rft.spage=e0181414&rft.epage=e0181414&rft.pages=e0181414-e0181414&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0181414&rft_dat=%3Cgale_plos_%3EA500574584%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1928759174&rft_id=info:pmid/28806423&rft_galeid=A500574584&rft_doaj_id=oai_doaj_org_article_bf4fbbccc59845b491dfd05d9f335dff&rfr_iscdi=true |