Use of QuantiFERON®-TB Gold in-tube culture supernatants for measurement of antibody responses
QuantiFERON®-TB Gold in-tube (QFT-GIT) supernatants may be important samples for use in assessment of anti-tuberculosis (TB) antibodies when only limited volumes of blood can be collected and when a combination of antibody and cytokine measurements are required. These analytes, when used together, m...
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| Veröffentlicht in: | PloS one 2017-11, Vol.12 (11), p.e0188396-e0188396 |
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| creator | Kimuda, Simon G Andia-Biraro, Irene Egesa, Moses Bagaya, Bernard S Raynes, John G Levin, Jonathan Elliott, Alison M Cose, Stephen |
| description | QuantiFERON®-TB Gold in-tube (QFT-GIT) supernatants may be important samples for use in assessment of anti-tuberculosis (TB) antibodies when only limited volumes of blood can be collected and when a combination of antibody and cytokine measurements are required. These analytes, when used together, may also have the potential to differentiate active pulmonary TB (APTB) from latent TB infection (LTBI). However, few studies have explored the use of QFT-GIT supernatants for investigations of antibody responses. This study determined the correlation and agreement between anti-CFP-10 and anti-ESAT-6 antibody concentrations in QFT-GIT nil supernatant and serum pairs from 68 TB household contacts. We also explored the ability of Mycobacterium tuberculosis (M.tb) specific antibodies, or ratios of antibody to interferon gamma (IFN-γ) in QFT-GIT supernatants, to differentiate 97 APTB cases from 58 individuals with LTBI. Sputum smear microscopy was used to define APTB, whereas the QFT-GIT and tuberculin skin test were used to define LTBI. There were strong and statistically significant correlations between anti-CFP-10 and anti-ESAT-6 antibodies in unstimulated QFT-GIT supernatants and sera (r = 0.89; p |
| doi_str_mv | 10.1371/journal.pone.0188396 |
| format | Article |
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These analytes, when used together, may also have the potential to differentiate active pulmonary TB (APTB) from latent TB infection (LTBI). However, few studies have explored the use of QFT-GIT supernatants for investigations of antibody responses. This study determined the correlation and agreement between anti-CFP-10 and anti-ESAT-6 antibody concentrations in QFT-GIT nil supernatant and serum pairs from 68 TB household contacts. We also explored the ability of Mycobacterium tuberculosis (M.tb) specific antibodies, or ratios of antibody to interferon gamma (IFN-γ) in QFT-GIT supernatants, to differentiate 97 APTB cases from 58 individuals with LTBI. Sputum smear microscopy was used to define APTB, whereas the QFT-GIT and tuberculin skin test were used to define LTBI. There were strong and statistically significant correlations between anti-CFP-10 and anti-ESAT-6 antibodies in unstimulated QFT-GIT supernatants and sera (r = 0.89; p<0.0001 for both), and no significant differences in antibody concentration between them. Anti-CFP-10 & anti-ESAT-6 antibodies differentiated APTB from LTBI with sensitivities of 88.7% & 71.1% and specificities of 41.4% & 51.7% respectively. Anti-CFP-10 antibody/M.tb specific IFN-γ and anti-ESAT-6 antibody/M.tb specific IFN-γ ratios had sensitivities of 48.5% & 54.6% and specificities of 89.7% and 75.9% respectively. We conclude that QFT-GIT nil supernatants may be used in the place of sera when measuring antibody responses, reducing blood volumes needed for such investigations. Antibodies in QFT-GIT nil supernatants on their own discriminate APTB from LTBI with high sensitivity but have poor specificity, whereas the reverse is true when antibodies are used in combination with M.tb specific cytokines. Further antibody and antibody/cytokine combinations need to be explored to achieve better diagnostic accuracy.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0188396</identifier><identifier>PMID: 29161328</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; Adolescent ; Adult ; Aged ; AIDS ; Analytical chemistry ; Antibodies ; Antibodies, Anti-Idiotypic - immunology ; Antibodies, Anti-Idiotypic - isolation & purification ; Antibody Formation - immunology ; Antigens ; Antigens, Bacterial - immunology ; Antigens, Bacterial - isolation & purification ; Bacterial Proteins - immunology ; Bacterial Proteins - isolation & purification ; Biology and Life Sciences ; Blood ; Care and treatment ; Child ; Child, Preschool ; Correlation ; Correlation analysis ; Cytokines ; Diagnosis ; Diagnostic systems ; ESAT-6 antigen ; Female ; Health sciences ; HIV ; Human immunodeficiency virus ; Humans ; Hygiene ; Immunoassay ; Immunoglobulins ; Infant ; Infections ; Interferon ; Interferon-gamma - immunology ; Latent Tuberculosis - blood ; Latent Tuberculosis - immunology ; Latent Tuberculosis - microbiology ; Male ; Medicine ; Medicine and Health Sciences ; Methods ; Microscopy ; Middle Aged ; Mycobacterium tuberculosis ; Research and Analysis Methods ; Sensitivity ; Skin ; Skin tests ; Smear ; Sputum ; Sputum - immunology ; Sputum - microbiology ; Statistical analysis ; Statistical methods ; Tuberculin ; Tuberculosis ; Tuberculosis, Pulmonary - blood ; Tuberculosis, Pulmonary - immunology ; Tuberculosis, Pulmonary - microbiology ; Vaccines ; Young Adult ; γ-Interferon</subject><ispartof>PloS one, 2017-11, Vol.12 (11), p.e0188396-e0188396</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Kimuda 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 Kimuda et al 2017 Kimuda et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-e15691601fcf9cc2ff07db660ab92cf4705e3a0198ab17a5890a8ded69bb0b63</citedby><cites>FETCH-LOGICAL-c692t-e15691601fcf9cc2ff07db660ab92cf4705e3a0198ab17a5890a8ded69bb0b63</cites><orcidid>0000-0001-6818-617X</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/PMC5697869/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697869/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29161328$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Cardona, Pere-Joan</contributor><creatorcontrib>Kimuda, Simon G</creatorcontrib><creatorcontrib>Andia-Biraro, Irene</creatorcontrib><creatorcontrib>Egesa, Moses</creatorcontrib><creatorcontrib>Bagaya, Bernard S</creatorcontrib><creatorcontrib>Raynes, John G</creatorcontrib><creatorcontrib>Levin, Jonathan</creatorcontrib><creatorcontrib>Elliott, Alison M</creatorcontrib><creatorcontrib>Cose, Stephen</creatorcontrib><title>Use of QuantiFERON®-TB Gold in-tube culture supernatants for measurement of antibody responses</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>QuantiFERON®-TB Gold in-tube (QFT-GIT) supernatants may be important samples for use in assessment of anti-tuberculosis (TB) antibodies when only limited volumes of blood can be collected and when a combination of antibody and cytokine measurements are required. These analytes, when used together, may also have the potential to differentiate active pulmonary TB (APTB) from latent TB infection (LTBI). However, few studies have explored the use of QFT-GIT supernatants for investigations of antibody responses. This study determined the correlation and agreement between anti-CFP-10 and anti-ESAT-6 antibody concentrations in QFT-GIT nil supernatant and serum pairs from 68 TB household contacts. We also explored the ability of Mycobacterium tuberculosis (M.tb) specific antibodies, or ratios of antibody to interferon gamma (IFN-γ) in QFT-GIT supernatants, to differentiate 97 APTB cases from 58 individuals with LTBI. Sputum smear microscopy was used to define APTB, whereas the QFT-GIT and tuberculin skin test were used to define LTBI. There were strong and statistically significant correlations between anti-CFP-10 and anti-ESAT-6 antibodies in unstimulated QFT-GIT supernatants and sera (r = 0.89; p<0.0001 for both), and no significant differences in antibody concentration between them. Anti-CFP-10 & anti-ESAT-6 antibodies differentiated APTB from LTBI with sensitivities of 88.7% & 71.1% and specificities of 41.4% & 51.7% respectively. Anti-CFP-10 antibody/M.tb specific IFN-γ and anti-ESAT-6 antibody/M.tb specific IFN-γ ratios had sensitivities of 48.5% & 54.6% and specificities of 89.7% and 75.9% respectively. We conclude that QFT-GIT nil supernatants may be used in the place of sera when measuring antibody responses, reducing blood volumes needed for such investigations. Antibodies in QFT-GIT nil supernatants on their own discriminate APTB from LTBI with high sensitivity but have poor specificity, whereas the reverse is true when antibodies are used in combination with M.tb specific cytokines. Further antibody and antibody/cytokine combinations need to be explored to achieve better diagnostic accuracy.</description><subject>Acquired immune deficiency syndrome</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>AIDS</subject><subject>Analytical chemistry</subject><subject>Antibodies</subject><subject>Antibodies, Anti-Idiotypic - immunology</subject><subject>Antibodies, Anti-Idiotypic - isolation & purification</subject><subject>Antibody Formation - immunology</subject><subject>Antigens</subject><subject>Antigens, Bacterial - immunology</subject><subject>Antigens, Bacterial - isolation & purification</subject><subject>Bacterial Proteins - immunology</subject><subject>Bacterial Proteins - isolation & purification</subject><subject>Biology and Life Sciences</subject><subject>Blood</subject><subject>Care and treatment</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Correlation</subject><subject>Correlation analysis</subject><subject>Cytokines</subject><subject>Diagnosis</subject><subject>Diagnostic systems</subject><subject>ESAT-6 antigen</subject><subject>Female</subject><subject>Health sciences</subject><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Hygiene</subject><subject>Immunoassay</subject><subject>Immunoglobulins</subject><subject>Infant</subject><subject>Infections</subject><subject>Interferon</subject><subject>Interferon-gamma - immunology</subject><subject>Latent Tuberculosis - blood</subject><subject>Latent Tuberculosis - immunology</subject><subject>Latent Tuberculosis - microbiology</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Methods</subject><subject>Microscopy</subject><subject>Middle Aged</subject><subject>Mycobacterium tuberculosis</subject><subject>Research and Analysis Methods</subject><subject>Sensitivity</subject><subject>Skin</subject><subject>Skin tests</subject><subject>Smear</subject><subject>Sputum</subject><subject>Sputum - immunology</subject><subject>Sputum - microbiology</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Tuberculin</subject><subject>Tuberculosis</subject><subject>Tuberculosis, Pulmonary - blood</subject><subject>Tuberculosis, Pulmonary - immunology</subject><subject>Tuberculosis, Pulmonary - microbiology</subject><subject>Vaccines</subject><subject>Young Adult</subject><subject>γ-Interferon</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>eNqNk8Fu1DAQhiMEomXhDRBEQkJwyGLHiWNfkErVlpUqVpSFq-U4492sknixnap9KR6CJ8Nh02qDekA5JLK_-Wfmz0wUvcRojkmBP2xNbzvZzHemgznCjBFOH0XHmJM0oSkijw--j6Jnzm0Rygmj9Gl0lHJMMUnZcSS-O4iNjr_2svP1-dnV8svvX8nqU3xhmiquu8T3JcSqb3xvIXb9DkJSH1gXa2PjFqQLFy10flAZNEpT3cYWXKjLgXsePdGycfBifM-i1fnZ6vRzcrm8WJyeXCaK8tQngHMaakJYK82VSrVGRVVSimTJU6WzAuVAJMKcyRIXMmccSVZBRXlZopKSWfR6L7trjBOjNU5gTguUIZKSQCz2RGXkVuxs3Up7K4ysxd8DY9dCWl-rBgRJi6xkMqNMsywlSILirFJFjlSZy2DiLPo4ZuvLFioVureymYhOb7p6I9bmWoQmC0Z5EHg3CljzswfnRVs7BU0jOzD9vu6MIsaHut_8gz7c3UitZWig7rQJedUgKk5ynGOek3Rwaf4AFZ4K2lqFOdJ1OJ8EvJ8EBMbDjV_L3jmx-Hb1_-zyx5R9e8BuQDZ-40zT-zoMzRTM9qCyxjkL-t5kjMSwBnduiGENxLgGIezV4Q-6D7qbe_IHhowC_w</recordid><startdate>20171121</startdate><enddate>20171121</enddate><creator>Kimuda, Simon G</creator><creator>Andia-Biraro, Irene</creator><creator>Egesa, Moses</creator><creator>Bagaya, Bernard S</creator><creator>Raynes, John G</creator><creator>Levin, Jonathan</creator><creator>Elliott, Alison M</creator><creator>Cose, Stephen</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/0000-0001-6818-617X</orcidid></search><sort><creationdate>20171121</creationdate><title>Use of QuantiFERON®-TB Gold in-tube culture supernatants for measurement of antibody responses</title><author>Kimuda, Simon G ; Andia-Biraro, Irene ; Egesa, Moses ; Bagaya, Bernard S ; Raynes, John G ; Levin, Jonathan ; Elliott, Alison M ; Cose, Stephen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-e15691601fcf9cc2ff07db660ab92cf4705e3a0198ab17a5890a8ded69bb0b63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>AIDS</topic><topic>Analytical chemistry</topic><topic>Antibodies</topic><topic>Antibodies, Anti-Idiotypic - 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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>Kimuda, Simon G</au><au>Andia-Biraro, Irene</au><au>Egesa, Moses</au><au>Bagaya, Bernard S</au><au>Raynes, John G</au><au>Levin, Jonathan</au><au>Elliott, Alison M</au><au>Cose, Stephen</au><au>Cardona, Pere-Joan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Use of QuantiFERON®-TB Gold in-tube culture supernatants for measurement of antibody responses</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-11-21</date><risdate>2017</risdate><volume>12</volume><issue>11</issue><spage>e0188396</spage><epage>e0188396</epage><pages>e0188396-e0188396</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>QuantiFERON®-TB Gold in-tube (QFT-GIT) supernatants may be important samples for use in assessment of anti-tuberculosis (TB) antibodies when only limited volumes of blood can be collected and when a combination of antibody and cytokine measurements are required. These analytes, when used together, may also have the potential to differentiate active pulmonary TB (APTB) from latent TB infection (LTBI). However, few studies have explored the use of QFT-GIT supernatants for investigations of antibody responses. This study determined the correlation and agreement between anti-CFP-10 and anti-ESAT-6 antibody concentrations in QFT-GIT nil supernatant and serum pairs from 68 TB household contacts. We also explored the ability of Mycobacterium tuberculosis (M.tb) specific antibodies, or ratios of antibody to interferon gamma (IFN-γ) in QFT-GIT supernatants, to differentiate 97 APTB cases from 58 individuals with LTBI. Sputum smear microscopy was used to define APTB, whereas the QFT-GIT and tuberculin skin test were used to define LTBI. There were strong and statistically significant correlations between anti-CFP-10 and anti-ESAT-6 antibodies in unstimulated QFT-GIT supernatants and sera (r = 0.89; p<0.0001 for both), and no significant differences in antibody concentration between them. Anti-CFP-10 & anti-ESAT-6 antibodies differentiated APTB from LTBI with sensitivities of 88.7% & 71.1% and specificities of 41.4% & 51.7% respectively. Anti-CFP-10 antibody/M.tb specific IFN-γ and anti-ESAT-6 antibody/M.tb specific IFN-γ ratios had sensitivities of 48.5% & 54.6% and specificities of 89.7% and 75.9% respectively. We conclude that QFT-GIT nil supernatants may be used in the place of sera when measuring antibody responses, reducing blood volumes needed for such investigations. Antibodies in QFT-GIT nil supernatants on their own discriminate APTB from LTBI with high sensitivity but have poor specificity, whereas the reverse is true when antibodies are used in combination with M.tb specific cytokines. Further antibody and antibody/cytokine combinations need to be explored to achieve better diagnostic accuracy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29161328</pmid><doi>10.1371/journal.pone.0188396</doi><tpages>e0188396</tpages><orcidid>https://orcid.org/0000-0001-6818-617X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-11, Vol.12 (11), p.e0188396-e0188396 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1967040323 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acquired immune deficiency syndrome Adolescent Adult Aged AIDS Analytical chemistry Antibodies Antibodies, Anti-Idiotypic - immunology Antibodies, Anti-Idiotypic - isolation & purification Antibody Formation - immunology Antigens Antigens, Bacterial - immunology Antigens, Bacterial - isolation & purification Bacterial Proteins - immunology Bacterial Proteins - isolation & purification Biology and Life Sciences Blood Care and treatment Child Child, Preschool Correlation Correlation analysis Cytokines Diagnosis Diagnostic systems ESAT-6 antigen Female Health sciences HIV Human immunodeficiency virus Humans Hygiene Immunoassay Immunoglobulins Infant Infections Interferon Interferon-gamma - immunology Latent Tuberculosis - blood Latent Tuberculosis - immunology Latent Tuberculosis - microbiology Male Medicine Medicine and Health Sciences Methods Microscopy Middle Aged Mycobacterium tuberculosis Research and Analysis Methods Sensitivity Skin Skin tests Smear Sputum Sputum - immunology Sputum - microbiology Statistical analysis Statistical methods Tuberculin Tuberculosis Tuberculosis, Pulmonary - blood Tuberculosis, Pulmonary - immunology Tuberculosis, Pulmonary - microbiology Vaccines Young Adult γ-Interferon |
| title | Use of QuantiFERON®-TB Gold in-tube culture supernatants for measurement of antibody responses |
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