PMID- 35398886
OWN - NLM
STAT- MEDLINE
DCOM- 20220712
LR  - 20240211
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 52
IP  - 7
DP  - 2022 Jul
TI  - Host transcriptomic signatures of tuberculosis can predict immune reconstitution 
      inflammatory syndrome in HIV patients.
PG  - 1112-1119
LID - 10.1002/eji.202249815 [doi]
AB  - Immune reconstitution inflammatory syndrome (IRIS) can be a complication of 
      antiretroviral therapy (ART) in patients with advanced HIV, but its pathogenesis 
      is uncertain. In tuberculosis (TB) endemic countries, IRIS is often associated 
      with mycobacterial infections or Bacille-Calmette-Guerin (BCG) vaccination in 
      children. With no predictive or confirmatory tests at present, IRIS remains a 
      diagnosis of exclusion. We tested whether RISK6 and Sweeney3, validated 
      immune-based blood transcriptomic signatures for TB, could predict or diagnose 
      IRIS in HIV+ children and adults. Transcripts were measured by RT-qPCR in 
      BCG-vaccinated 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. In children, 
      RISK6 and Sweeney3 discriminated IRIS cases from non-IRIS controls before ART, 
      and at diagnosis. In adults with TB, RISK6 discriminated IRIS cases from controls 
      after half-week on ART and at TB-IRIS onset. In adults with TBM, only Sweeney3 
      discriminated IRIS cases from controls before ART, while both signatures 
      distinguished cases from controls at TB-IRIS onset. Parsimonious whole blood 
      transcriptomic signatures for TB showed potential to predict and diagnose IRIS in 
      HIV+ children and adults.
CI  - (c) 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
FAU - Mbandi, Stanley Kimbung
AU  - Mbandi SK
AD  - 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.
FAU - Painter, Hannah
AU  - Painter H
AD  - Department of Infection Biology, London School of Hygiene & Tropical Medicine, 
      London, UK.
FAU - Penn-Nicholson, Adam
AU  - Penn-Nicholson A
AD  - 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.
FAU - Toefy, Asma
AU  - Toefy A
AD  - 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.
FAU - Erasmus, Mzwandile
AU  - Erasmus M
AD  - 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.
FAU - Hanekom, Willem A
AU  - Hanekom WA
AD  - 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.
FAU - Scriba, Thomas J
AU  - Scriba TJ
AD  - 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.
FAU - Lai, Rachel P J
AU  - Lai RPJ
AD  - Department of Infectious Diseases, Imperial College London, London, UK.
FAU - Marais, Suzaan
AU  - Marais S
AD  - Wellcome Centre for Infectious Diseases Research in Africa, University of Cape 
      Town, Observatory, South Africa.
AD  - Institute of Infectious Disease and Molecular Medicine and Department of 
      Medicine, University of Cape Town, Observatory, South Africa.
FAU - Fletcher, Helen A
AU  - Fletcher HA
AD  - Department of Infection Biology, London School of Hygiene & Tropical Medicine, 
      London, UK.
FAU - Meintjes, Graeme
AU  - Meintjes G
AD  - Wellcome Centre for Infectious Diseases Research in Africa, University of Cape 
      Town, Observatory, South Africa.
AD  - Institute of Infectious Disease and Molecular Medicine and Department of 
      Medicine, University of Cape Town, Observatory, South Africa.
FAU - Wilkinson, Robert J
AU  - Wilkinson RJ
AD  - Department of Infectious Diseases, Imperial College London, London, UK.
AD  - Wellcome Centre for Infectious Diseases Research in Africa, University of Cape 
      Town, Observatory, South Africa.
AD  - Institute of Infectious Disease and Molecular Medicine and Department of 
      Medicine, University of Cape Town, Observatory, South Africa.
AD  - Francis Crick Institute, London, UK.
FAU - Cotton, Mark F
AU  - Cotton MF
AD  - Family Center for Research with Ubuntu, Department of Pediatrics & Child Health, 
      Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, 
      South Africa.
FAU - Pahwa, Savita
AU  - Pahwa S
AD  - Department of Microbiology and Immunology, Miami Center for AIDS Research, 
      University of Miami Miller School of Medicine, Miami, Florida, USA.
FAU - Cameron, Mark J
AU  - Cameron MJ
AD  - Department of Population & Quantitative Health Sciences, Case Western Reserve 
      University School of Medicine, Cleveland, Ohio, USA.
FAU - Nemes, Elisa
AU  - Nemes E
AUID- ORCID: 0000-0003-1662-4961
AD  - 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.
LA  - eng
GR  - 098316/WT_/Wellcome Trust/United Kingdom
GR  - 203135/Z/16/Z/WT_/Wellcome Trust/United Kingdom
GR  - HHSN275201800001C/HD/NICHD NIH HHS/United States
GR  - UM1 AI068632/AI/NIAID NIH HHS/United States
GR  - UM1 AI068616/AI/NIAID NIH HHS/United States
GR  - MR/R008922/1/MRC_/Medical Research Council/United Kingdom
GR  - MR/N013638/1/MRC_/Medical Research Council/United Kingdom
GR  - HHSN275201800001I/HD/NICHD NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 214321/Z/18/Z/WT_/Wellcome Trust/United Kingdom
GR  - CRUK_/Cancer Research UK/United Kingdom
GR  - UM1 AI106716/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220427
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (BCG Vaccine)
SB  - IM
MH  - Adult
MH  - BCG Vaccine
MH  - Child
MH  - *HIV Infections/complications/drug therapy
MH  - Humans
MH  - *Immune Reconstitution Inflammatory Syndrome/complications/diagnosis
MH  - Transcriptome
MH  - *Tuberculosis/diagnosis
PMC - PMC9276552
MID - NIHMS1796795
OTO - NOTNLM
OT  - Bacille-Calmette-Guerin
OT  - host biomarker
OT  - immune reconstitution inflammatory syndrome
OT  - transcriptomic signature
OT  - tuberculosis
COIS- TJS, APN, and WAH are coinventors of a patent of the RISK6 signature. The other 
      authors declare no conflict of interest.
EDAT- 2022/04/11 06:00
MHDA- 2022/07/14 06:00
PMCR- 2022/10/07
CRDT- 2022/04/10 20:33
PHST- 2022/04/06 00:00 [revised]
PHST- 2022/01/14 00:00 [received]
PHST- 2022/04/07 00:00 [accepted]
PHST- 2022/04/11 06:00 [pubmed]
PHST- 2022/07/14 06:00 [medline]
PHST- 2022/04/10 20:33 [entrez]
PHST- 2022/10/07 00:00 [pmc-release]
AID - EJI5270 [pii]
AID - 10.1002/eji.202249815 [doi]
PST - ppublish
SO  - Eur J Immunol. 2022 Jul;52(7):1112-1119. doi: 10.1002/eji.202249815. Epub 2022 
      Apr 27.