Leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a global health problem. At present, prior exposure to Mtb can be determined by blood-based interferon-gamma release assay (IGRA), but active TB is not always detectable by blood tests such as CRP and ESR. This study was undertaken to i...
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description | Tuberculosis (TB) caused by
Mycobacterium tuberculosis
(Mtb) is a global health problem. At present, prior exposure to Mtb can be determined by blood-based interferon-gamma release assay (IGRA), but active TB is not always detectable by blood tests such as CRP and ESR. This study was undertaken to investigate whether leucine-rich alpha-2 glycoprotein (LRG), a new inflammatory biomarker, could be used to assess active disease of TB. Cynomolgus macaques pretreated with or without Bacille Calmette-Guerin (BCG) vaccination were inoculated with Mtb to induce active TB. Blood was collected over time from these animals and levels of LRG as well as CRP and ESR were quantified. In the macaques without BCG vaccination, Mtb inoculation caused extensive TB and significantly increased plasma CRP and LRG levels, but not ESR. In the macaques with BCG vaccination, whereas Mtb challenge caused pulmonary TB, only LRG levels were significantly elevated. By immunohistochemical analysis of the lung, LRG was visualized in epithelioid cells and giant cells of the granulation tissue. In humans, serum LRG levels in TB patients were significantly higher than those in healthy controls and declined one month after anti-tubercular therapy. These findings suggest that LRG is a promising biomarker when performed following IGRA for the detection of active TB. |
doi_str_mv | 10.1038/s41598-020-60450-3 |
format | Article |
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Mycobacterium tuberculosis
(Mtb) is a global health problem. At present, prior exposure to Mtb can be determined by blood-based interferon-gamma release assay (IGRA), but active TB is not always detectable by blood tests such as CRP and ESR. This study was undertaken to investigate whether leucine-rich alpha-2 glycoprotein (LRG), a new inflammatory biomarker, could be used to assess active disease of TB. Cynomolgus macaques pretreated with or without Bacille Calmette-Guerin (BCG) vaccination were inoculated with Mtb to induce active TB. Blood was collected over time from these animals and levels of LRG as well as CRP and ESR were quantified. In the macaques without BCG vaccination, Mtb inoculation caused extensive TB and significantly increased plasma CRP and LRG levels, but not ESR. In the macaques with BCG vaccination, whereas Mtb challenge caused pulmonary TB, only LRG levels were significantly elevated. By immunohistochemical analysis of the lung, LRG was visualized in epithelioid cells and giant cells of the granulation tissue. In humans, serum LRG levels in TB patients were significantly higher than those in healthy controls and declined one month after anti-tubercular therapy. These findings suggest that LRG is a promising biomarker when performed following IGRA for the detection of active TB.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-60450-3</identifier><identifier>PMID: 32099022</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/51 ; 692/53/2421 ; 692/699/255/1856 ; 82/1 ; Animals ; Bacillus Calmette-Guerin vaccine ; BCG ; BCG Vaccine - immunology ; Biomarkers ; Biomarkers - blood ; Blood ; Blood Sedimentation ; C-Reactive Protein - analysis ; Case-Control Studies ; Disease Models, Animal ; Giant cells ; Global health ; Glycoproteins ; Glycoproteins - blood ; Humanities and Social Sciences ; Humans ; Immunization ; Inflammation ; Inoculation ; Interleukin-6 - blood ; Leucine ; Lung - metabolism ; Lung - pathology ; Macaca fascicularis ; multidisciplinary ; Mycobacterium tuberculosis - pathogenicity ; Science ; Science (multidisciplinary) ; Tuberculosis ; Tuberculosis - blood ; Tuberculosis - diagnosis ; Vaccination ; γ-Interferon</subject><ispartof>Scientific reports, 2020-02, Vol.10 (1), p.3384-3384, Article 3384</ispartof><rights>The Author(s) 2020</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-13e189e58d7ea52bb2a975ecb28a98ba3ddb49e3063fd9710026292fff1504123</citedby><cites>FETCH-LOGICAL-c540t-13e189e58d7ea52bb2a975ecb28a98ba3ddb49e3063fd9710026292fff1504123</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/PMC7042324/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042324/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,41101,42170,51557,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32099022$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fujimoto, Minoru</creatorcontrib><creatorcontrib>Matsumoto, Tomoshige</creatorcontrib><creatorcontrib>Serada, Satoshi</creatorcontrib><creatorcontrib>Tsujimura, Yusuke</creatorcontrib><creatorcontrib>Hashimoto, Shoji</creatorcontrib><creatorcontrib>Yasutomi, Yasuhiro</creatorcontrib><creatorcontrib>Naka, Tetsuji</creatorcontrib><title>Leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Tuberculosis (TB) caused by
Mycobacterium tuberculosis
(Mtb) is a global health problem. At present, prior exposure to Mtb can be determined by blood-based interferon-gamma release assay (IGRA), but active TB is not always detectable by blood tests such as CRP and ESR. This study was undertaken to investigate whether leucine-rich alpha-2 glycoprotein (LRG), a new inflammatory biomarker, could be used to assess active disease of TB. Cynomolgus macaques pretreated with or without Bacille Calmette-Guerin (BCG) vaccination were inoculated with Mtb to induce active TB. Blood was collected over time from these animals and levels of LRG as well as CRP and ESR were quantified. In the macaques without BCG vaccination, Mtb inoculation caused extensive TB and significantly increased plasma CRP and LRG levels, but not ESR. In the macaques with BCG vaccination, whereas Mtb challenge caused pulmonary TB, only LRG levels were significantly elevated. By immunohistochemical analysis of the lung, LRG was visualized in epithelioid cells and giant cells of the granulation tissue. In humans, serum LRG levels in TB patients were significantly higher than those in healthy controls and declined one month after anti-tubercular therapy. These findings suggest that LRG is a promising biomarker when performed following IGRA for the detection of active TB.</description><subject>13/51</subject><subject>692/53/2421</subject><subject>692/699/255/1856</subject><subject>82/1</subject><subject>Animals</subject><subject>Bacillus Calmette-Guerin vaccine</subject><subject>BCG</subject><subject>BCG Vaccine - immunology</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Blood</subject><subject>Blood Sedimentation</subject><subject>C-Reactive Protein - analysis</subject><subject>Case-Control Studies</subject><subject>Disease Models, Animal</subject><subject>Giant cells</subject><subject>Global health</subject><subject>Glycoproteins</subject><subject>Glycoproteins - blood</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Immunization</subject><subject>Inflammation</subject><subject>Inoculation</subject><subject>Interleukin-6 - blood</subject><subject>Leucine</subject><subject>Lung - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fujimoto, Minoru</au><au>Matsumoto, Tomoshige</au><au>Serada, Satoshi</au><au>Tsujimura, Yusuke</au><au>Hashimoto, Shoji</au><au>Yasutomi, Yasuhiro</au><au>Naka, Tetsuji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-02-25</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>3384</spage><epage>3384</epage><pages>3384-3384</pages><artnum>3384</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Tuberculosis (TB) caused by
Mycobacterium tuberculosis
(Mtb) is a global health problem. At present, prior exposure to Mtb can be determined by blood-based interferon-gamma release assay (IGRA), but active TB is not always detectable by blood tests such as CRP and ESR. This study was undertaken to investigate whether leucine-rich alpha-2 glycoprotein (LRG), a new inflammatory biomarker, could be used to assess active disease of TB. Cynomolgus macaques pretreated with or without Bacille Calmette-Guerin (BCG) vaccination were inoculated with Mtb to induce active TB. Blood was collected over time from these animals and levels of LRG as well as CRP and ESR were quantified. In the macaques without BCG vaccination, Mtb inoculation caused extensive TB and significantly increased plasma CRP and LRG levels, but not ESR. In the macaques with BCG vaccination, whereas Mtb challenge caused pulmonary TB, only LRG levels were significantly elevated. By immunohistochemical analysis of the lung, LRG was visualized in epithelioid cells and giant cells of the granulation tissue. In humans, serum LRG levels in TB patients were significantly higher than those in healthy controls and declined one month after anti-tubercular therapy. These findings suggest that LRG is a promising biomarker when performed following IGRA for the detection of active TB.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32099022</pmid><doi>10.1038/s41598-020-60450-3</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 13/51 692/53/2421 692/699/255/1856 82/1 Animals Bacillus Calmette-Guerin vaccine BCG BCG Vaccine - immunology Biomarkers Biomarkers - blood Blood Blood Sedimentation C-Reactive Protein - analysis Case-Control Studies Disease Models, Animal Giant cells Global health Glycoproteins Glycoproteins - blood Humanities and Social Sciences Humans Immunization Inflammation Inoculation Interleukin-6 - blood Leucine Lung - metabolism Lung - pathology Macaca fascicularis multidisciplinary Mycobacterium tuberculosis - pathogenicity Science Science (multidisciplinary) Tuberculosis Tuberculosis - blood Tuberculosis - diagnosis Vaccination γ-Interferon |
title | Leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis |
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