Improving T-cell assays for the diagnosis of latent TB infection: potential of a diagnostic test based on IP-10
There is a need for simple tools such as the M.tuberculosis specific IFN-gamma release assays (IGRA) to improve diagnosis of M.tuberculosis-infection in children. The aim of the study was to evaluate the performance of an IP-10 and IL-2 based tests for the diagnosis of M.tuberculosis-infection in re...
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| creator | Ruhwald, Morten Petersen, Janne Kofoed, Kristian Nakaoka, Hiroshi Cuevas, Luis Eduardo Lawson, Lovett Squire, Stephen Bertil Eugen-Olsen, Jesper Ravn, Pernille |
| description | There is a need for simple tools such as the M.tuberculosis specific IFN-gamma release assays (IGRA) to improve diagnosis of M.tuberculosis-infection in children. The aim of the study was to evaluate the performance of an IP-10 and IL-2 based tests for the diagnosis of M.tuberculosis-infection in recently exposed children from Nigeria.
Samples were obtained from 59 children at high risk of infection with M.tuberculosis (contacts of adults with smear and culture-positive tuberculosis) and 61 at low risk (contacts of smear-negative/culture-positive tuberculosis or community controls). IP-10 and IL-2 was measured in plasma after stimulation of whole-blood with M.tuberculosis specific antigens and mitogen. Previously developed criteria for positive IP-10 and IL-2 tests were used and the diagnostic performances of the IP-10 and IL-2 tests were compared with the Quantiferon In-Tube (QFT-IT) and the Tuberculin Skin Tests (TST). In response to M.tuberculosis specific antigens, the high-risk children expressed significantly higher levels of IP-10 (1358 pg/ml[IQR 278-2535 pg/ml]) and IL-2 (164 pg/ml[11-590 pg/ml]) than low risk groups 149 pg/ml(25-497 pg/ml), and 0 pg/ml(0-3 pg/ml), respectively. There was excellent agreement (>89%,k>0.80) between IP-10, IL-2 tests and QFT-IT, better than with TST (>74%,k>0.49). The IP-10 and IL-2 responses were strongly associated with M.tuberculosis exposure and with grade of infectiousness of the index cases (p |
| doi_str_mv | 10.1371/journal.pone.0002858 |
| format | Article |
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Samples were obtained from 59 children at high risk of infection with M.tuberculosis (contacts of adults with smear and culture-positive tuberculosis) and 61 at low risk (contacts of smear-negative/culture-positive tuberculosis or community controls). IP-10 and IL-2 was measured in plasma after stimulation of whole-blood with M.tuberculosis specific antigens and mitogen. Previously developed criteria for positive IP-10 and IL-2 tests were used and the diagnostic performances of the IP-10 and IL-2 tests were compared with the Quantiferon In-Tube (QFT-IT) and the Tuberculin Skin Tests (TST). In response to M.tuberculosis specific antigens, the high-risk children expressed significantly higher levels of IP-10 (1358 pg/ml[IQR 278-2535 pg/ml]) and IL-2 (164 pg/ml[11-590 pg/ml]) than low risk groups 149 pg/ml(25-497 pg/ml), and 0 pg/ml(0-3 pg/ml), respectively. There was excellent agreement (>89%,k>0.80) between IP-10, IL-2 tests and QFT-IT, better than with TST (>74%,k>0.49). The IP-10 and IL-2 responses were strongly associated with M.tuberculosis exposure and with grade of infectiousness of the index cases (p<0.0001). IP-10, IL-2, and TST but not QFT-IT was associated with age of the child in the low risk groups (p<0.02).
IP-10 is expressed in high levels and results of the IP-10 test were comparable to the QFT-IT. IL-2 was released in low amounts in response to the antigens and not in response to the mitogen therefore IL-2 seems a less useful marker. We have demonstrated that IP-10 and possibly IL-2 could be alternative or adjunct markers to IFN-gamma in the diagnosis infection with M.tuberculosis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0002858</identifier><identifier>PMID: 18682747</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Adults ; Antigens ; Biomarkers ; Cell culture ; Chemokine CXCL10 - blood ; Chemokines ; Chemotherapy ; Child ; Child, Preschool ; Children ; Cytokines ; Diagnosis ; Diagnostic systems ; Diagnostic tests ; Enzyme-Linked Immunosorbent Assay ; Enzymes ; Female ; Health risks ; Hospitals ; Households ; Humans ; Immunology/Immune Response ; Infections ; Infectious diseases ; Infectious Diseases/Bacterial Infections ; Interferon ; Interferon-gamma - blood ; Interleukin 2 ; Interleukin-2 - blood ; IP-10 protein ; Lymphocytes T ; Male ; Medical diagnosis ; Medical research ; Medical tests ; Medicine ; Mycobacterium ; Mycobacterium tuberculosis ; Nigeria ; Performance evaluation ; Proteins ; Quality ; Respiratory Medicine/Respiratory Infections ; Risk ; Risk groups ; Sensitivity and Specificity ; Skin tests ; Smear ; Surveillance ; T cells ; T-Lymphocytes - immunology ; Th1 Cells - immunology ; Tuberculin ; Tuberculosis ; Tuberculosis - diagnosis ; Tuberculosis - immunology ; γ-Interferon</subject><ispartof>PloS one, 2008-08, Vol.3 (8), p.e2858-e2858</ispartof><rights>COPYRIGHT 2008 Public Library of Science</rights><rights>2008 Ruhwald et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (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>Ruhwald et al. 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c693t-f418a9a91dec99ced933a2142091eed5d482fbd6f84f56af26a711f65003c3f13</citedby><cites>FETCH-LOGICAL-c693t-f418a9a91dec99ced933a2142091eed5d482fbd6f84f56af26a711f65003c3f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483344/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483344/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2106,2932,23875,27933,27934,53800,53802</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18682747$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Dheda, Keertan</contributor><creatorcontrib>Ruhwald, Morten</creatorcontrib><creatorcontrib>Petersen, Janne</creatorcontrib><creatorcontrib>Kofoed, Kristian</creatorcontrib><creatorcontrib>Nakaoka, Hiroshi</creatorcontrib><creatorcontrib>Cuevas, Luis Eduardo</creatorcontrib><creatorcontrib>Lawson, Lovett</creatorcontrib><creatorcontrib>Squire, Stephen Bertil</creatorcontrib><creatorcontrib>Eugen-Olsen, Jesper</creatorcontrib><creatorcontrib>Ravn, Pernille</creatorcontrib><title>Improving T-cell assays for the diagnosis of latent TB infection: potential of a diagnostic test based on IP-10</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>There is a need for simple tools such as the M.tuberculosis specific IFN-gamma release assays (IGRA) to improve diagnosis of M.tuberculosis-infection in children. The aim of the study was to evaluate the performance of an IP-10 and IL-2 based tests for the diagnosis of M.tuberculosis-infection in recently exposed children from Nigeria.
Samples were obtained from 59 children at high risk of infection with M.tuberculosis (contacts of adults with smear and culture-positive tuberculosis) and 61 at low risk (contacts of smear-negative/culture-positive tuberculosis or community controls). IP-10 and IL-2 was measured in plasma after stimulation of whole-blood with M.tuberculosis specific antigens and mitogen. Previously developed criteria for positive IP-10 and IL-2 tests were used and the diagnostic performances of the IP-10 and IL-2 tests were compared with the Quantiferon In-Tube (QFT-IT) and the Tuberculin Skin Tests (TST). In response to M.tuberculosis specific antigens, the high-risk children expressed significantly higher levels of IP-10 (1358 pg/ml[IQR 278-2535 pg/ml]) and IL-2 (164 pg/ml[11-590 pg/ml]) than low risk groups 149 pg/ml(25-497 pg/ml), and 0 pg/ml(0-3 pg/ml), respectively. There was excellent agreement (>89%,k>0.80) between IP-10, IL-2 tests and QFT-IT, better than with TST (>74%,k>0.49). The IP-10 and IL-2 responses were strongly associated with M.tuberculosis exposure and with grade of infectiousness of the index cases (p<0.0001). IP-10, IL-2, and TST but not QFT-IT was associated with age of the child in the low risk groups (p<0.02).
IP-10 is expressed in high levels and results of the IP-10 test were comparable to the QFT-IT. IL-2 was released in low amounts in response to the antigens and not in response to the mitogen therefore IL-2 seems a less useful marker. We have demonstrated that IP-10 and possibly IL-2 could be alternative or adjunct markers to IFN-gamma in the diagnosis infection with M.tuberculosis.</description><subject>Adolescent</subject><subject>Adults</subject><subject>Antigens</subject><subject>Biomarkers</subject><subject>Cell culture</subject><subject>Chemokine CXCL10 - blood</subject><subject>Chemokines</subject><subject>Chemotherapy</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Cytokines</subject><subject>Diagnosis</subject><subject>Diagnostic systems</subject><subject>Diagnostic tests</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Enzymes</subject><subject>Female</subject><subject>Health risks</subject><subject>Hospitals</subject><subject>Households</subject><subject>Humans</subject><subject>Immunology/Immune Response</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Infectious Diseases/Bacterial Infections</subject><subject>Interferon</subject><subject>Interferon-gamma - 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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>Ruhwald, Morten</au><au>Petersen, Janne</au><au>Kofoed, Kristian</au><au>Nakaoka, Hiroshi</au><au>Cuevas, Luis Eduardo</au><au>Lawson, Lovett</au><au>Squire, Stephen Bertil</au><au>Eugen-Olsen, Jesper</au><au>Ravn, Pernille</au><au>Dheda, Keertan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improving T-cell assays for the diagnosis of latent TB infection: potential of a diagnostic test based on IP-10</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2008-08-06</date><risdate>2008</risdate><volume>3</volume><issue>8</issue><spage>e2858</spage><epage>e2858</epage><pages>e2858-e2858</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>There is a need for simple tools such as the M.tuberculosis specific IFN-gamma release assays (IGRA) to improve diagnosis of M.tuberculosis-infection in children. The aim of the study was to evaluate the performance of an IP-10 and IL-2 based tests for the diagnosis of M.tuberculosis-infection in recently exposed children from Nigeria.
Samples were obtained from 59 children at high risk of infection with M.tuberculosis (contacts of adults with smear and culture-positive tuberculosis) and 61 at low risk (contacts of smear-negative/culture-positive tuberculosis or community controls). IP-10 and IL-2 was measured in plasma after stimulation of whole-blood with M.tuberculosis specific antigens and mitogen. Previously developed criteria for positive IP-10 and IL-2 tests were used and the diagnostic performances of the IP-10 and IL-2 tests were compared with the Quantiferon In-Tube (QFT-IT) and the Tuberculin Skin Tests (TST). In response to M.tuberculosis specific antigens, the high-risk children expressed significantly higher levels of IP-10 (1358 pg/ml[IQR 278-2535 pg/ml]) and IL-2 (164 pg/ml[11-590 pg/ml]) than low risk groups 149 pg/ml(25-497 pg/ml), and 0 pg/ml(0-3 pg/ml), respectively. There was excellent agreement (>89%,k>0.80) between IP-10, IL-2 tests and QFT-IT, better than with TST (>74%,k>0.49). The IP-10 and IL-2 responses were strongly associated with M.tuberculosis exposure and with grade of infectiousness of the index cases (p<0.0001). IP-10, IL-2, and TST but not QFT-IT was associated with age of the child in the low risk groups (p<0.02).
IP-10 is expressed in high levels and results of the IP-10 test were comparable to the QFT-IT. IL-2 was released in low amounts in response to the antigens and not in response to the mitogen therefore IL-2 seems a less useful marker. We have demonstrated that IP-10 and possibly IL-2 could be alternative or adjunct markers to IFN-gamma in the diagnosis infection with M.tuberculosis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>18682747</pmid><doi>10.1371/journal.pone.0002858</doi><tpages>e2858</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2008-08, Vol.3 (8), p.e2858-e2858 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1317856676 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adolescent Adults Antigens Biomarkers Cell culture Chemokine CXCL10 - blood Chemokines Chemotherapy Child Child, Preschool Children Cytokines Diagnosis Diagnostic systems Diagnostic tests Enzyme-Linked Immunosorbent Assay Enzymes Female Health risks Hospitals Households Humans Immunology/Immune Response Infections Infectious diseases Infectious Diseases/Bacterial Infections Interferon Interferon-gamma - blood Interleukin 2 Interleukin-2 - blood IP-10 protein Lymphocytes T Male Medical diagnosis Medical research Medical tests Medicine Mycobacterium Mycobacterium tuberculosis Nigeria Performance evaluation Proteins Quality Respiratory Medicine/Respiratory Infections Risk Risk groups Sensitivity and Specificity Skin tests Smear Surveillance T cells T-Lymphocytes - immunology Th1 Cells - immunology Tuberculin Tuberculosis Tuberculosis - diagnosis Tuberculosis - immunology γ-Interferon |
| title | Improving T-cell assays for the diagnosis of latent TB infection: potential of a diagnostic test based on IP-10 |
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