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In tuberculosis (TB) endemic countries, IRIS is often associated with mycobacterial infections or Bacille\u2010Calmette\u2010Guerin (BCG) vaccination in children. With no predictive or confirmatory tests at present, IRIS remains a diagnosis of exclusion.<\/jats:p><jats:p>We tested whether RISK6 and Sweeney3, validated immune\u2010based blood transcriptomic signatures for TB, could predict or diagnose IRIS in HIV+ children and adults.<\/jats:p><jats:p>Transcripts were measured by RT\u2010qPCR in BCG\u2010vaccinated children and by microarray in HIV+ adults with TB including TB meningitis (TBM). Signature scores before ART initiation and up to IRIS diagnosis were compared between participants who did or did not develop IRIS.<\/jats:p><jats:p>In children, RISK6 and Sweeney3 discriminated IRIS cases from non\u2010IRIS controls before ART, and at diagnosis. In adults with TB, RISK6 discriminated IRIS cases from controls after half\u2010week on ART and at TB\u2010IRIS onset. In adults with TBM, only Sweeney3 discriminated IRIS cases from controls before ART, while both signatures distinguished cases from controls at TB\u2010IRIS onset.<\/jats:p><jats:p>Parsimonious whole blood transcriptomic signatures for TB showed potential to predict and diagnose IRIS in HIV+ children and adults.<\/jats:p>","DOI":"10.1002\/eji.202249815","type":"journal-article","created":{"date-parts":[[2022,4,10]],"date-time":"2022-04-10T06:19:02Z","timestamp":1649571542000},"page":"1112-1119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Host transcriptomic signatures of tuberculosis can predict immune reconstitution inflammatory syndrome in HIV patients"],"prefix":"10.1002","volume":"52","author":[{"given":"Stanley Kimbung","family":"Mbandi","sequence":"first","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative (SATVI) Institute of Infectious Disease and Molecular Medicine and Division of Immunology Department of Pathology University of Cape Town  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Painter","sequence":"additional","affiliation":[{"name":"Department of Infection Biology London School of Hygiene &amp; Tropical Medicine  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Penn\u2010Nicholson","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative (SATVI) Institute of Infectious Disease and Molecular Medicine and Division of Immunology Department of Pathology University of Cape Town  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asma","family":"Toefy","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative (SATVI) Institute of Infectious Disease and Molecular Medicine and Division of Immunology Department of Pathology University of Cape Town  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mzwandile","family":"Erasmus","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative (SATVI) Institute of Infectious Disease and Molecular Medicine and Division of Immunology Department of Pathology University of Cape Town  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willem A.","family":"Hanekom","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative (SATVI) Institute of Infectious Disease and Molecular Medicine and Division of Immunology Department of Pathology University of Cape Town  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Scriba","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative (SATVI) Institute of Infectious Disease and Molecular Medicine and Division of Immunology Department of Pathology University of Cape Town  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel P.J.","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Imperial College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzaan","family":"Marais","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Infectious Diseases Research in Africa University of Cape Town  Observatory South Africa"},{"name":"Institute of Infectious Disease and Molecular Medicine and Department of Medicine University of Cape Town  Observatory South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen A.","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Department of Infection Biology London School of Hygiene &amp; Tropical Medicine  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graeme","family":"Meintjes","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Infectious Diseases Research in Africa University of Cape Town  Observatory South Africa"},{"name":"Institute of Infectious Disease and Molecular Medicine and Department of Medicine University of Cape Town  Observatory South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Imperial College London  London UK"},{"name":"Wellcome Centre for Infectious Diseases Research in Africa University of Cape Town  Observatory South Africa"},{"name":"Institute of Infectious Disease and Molecular Medicine and Department of Medicine University of Cape Town  Observatory South Africa"},{"name":"Francis Crick Institute  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark F.","family":"Cotton","sequence":"additional","affiliation":[{"name":"Family Center for Research with Ubuntu Department of Pediatrics &amp; Child Health Faculty of Medicine and Health Sciences Stellenbosch University  Tygerberg South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Savita","family":"Pahwa","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Miami Center for AIDS Research University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J.","family":"Cameron","sequence":"additional","affiliation":[{"name":"Department of Population &amp; Quantitative Health Sciences Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1662-4961","authenticated-orcid":false,"given":"Elisa","family":"Nemes","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative (SATVI) Institute of Infectious Disease and Molecular Medicine and Division of Immunology Department of Pathology University of Cape Town  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"65","article-title":"Systemic inflammation associated with immune reconstitution inflammatory syndrome in persons living with HIV","volume":"11","author":"Vinhaes C. 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