PMID- 27932622
OWN - NLM
STAT- MEDLINE
DCOM- 20170509
LR  - 20220318
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 215
IP  - 5
DP  - 2017 Mar 1
TI  - Inflammasome Activation Underlying Central Nervous System Deterioration in 
      HIV-Associated Tuberculosis.
PG  - 677-686
LID - 10.1093/infdis/jiw561 [doi]
AB  - Tuberculous meningitis (TBM) is a frequent cause of meningitis in individuals 
      with human immunodeficiency virus (HIV) infection, resulting in death in 
      approximately 40% of affected patients. A severe complication of antiretroviral 
      therapy (ART) in these patients is neurological tuberculosis-immune 
      reconstitution inflammatory syndrome (IRIS), but its underlying cause remains 
      poorly understood. To investigate the pathogenesis of TBM-IRIS, we performed 
      longitudinal whole-blood microarray analysis of HIV-infected patients with TBM 
      and reflected the findings at the protein level. Patients in whom TBM-IRIS 
      eventually developed had significantly more abundant neutrophil-associated 
      transcripts, from before development of TBM-IRIS through IRIS symptom onset. 
      After ART initiation, a significantly higher abundance of transcripts associated 
      with canonical and noncanonical inflammasomes was detected in patients with 
      TBM-IRIS than in non-IRIS controls. Whole-blood transcriptome findings complement 
      protein measurement from the site of disease, which together suggest a dominant 
      role for the innate immune system in the pathogenesis of TBM-IRIS.
CI  - (c) The Author 2016. Published by Oxford University Press for the Infectious 
      Diseases Society of America.
FAU - Marais, Suzaan
AU  - Marais S
AD  - Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease 
      and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.
FAU - Lai, Rachel P J
AU  - Lai RPJ
AD  - Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease 
      and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.
FAU - Wilkinson, Katalin A
AU  - Wilkinson KA
AD  - Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease 
      and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.
AD  - Tuberculosis Laboratory, The Francis Crick Institute, 1 Midland Road, London, UK.
FAU - Meintjes, Graeme
AU  - Meintjes G
AD  - Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease 
      and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.
FAU - O'Garra, Anne
AU  - O'Garra A
AD  - Laboratory of Immuno regulation and Infection, The Francis Crick Institute, 
      London, UK.
AD  - National Heart and Lung Institute, Faculty of Medicine, Imperial College London, 
      London, United Kingdom.
FAU - Wilkinson, Robert J
AU  - Wilkinson RJ
AD  - Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease 
      and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.
AD  - Tuberculosis Laboratory, The Francis Crick Institute, 1 Midland Road, London, UK.
AD  - Department of Medicine, Imperial College London, United Kingdom.
LA  - eng
GR  - MC_U117565642/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Observational Study
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Inflammasomes)
RN  - 9007-36-7 (Complement System Proteins)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (CASP4 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases, Initiator)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
CIN - J Infect Dis. 2017 Mar 1;215(5):665-667. PMID: 27932621
MH  - Adult
MH  - Antiretroviral Therapy, Highly Active/adverse effects
MH  - Caspase 1/blood/cerebrospinal fluid
MH  - Caspase 3/blood/cerebrospinal fluid
MH  - Caspases, Initiator/blood/cerebrospinal fluid
MH  - Central Nervous System/*virology
MH  - Complement System Proteins/metabolism
MH  - Female
MH  - HIV Infections/drug therapy/*immunology/microbiology
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/*immunology
MH  - Inflammasomes/*blood
MH  - Lymphocyte Count
MH  - Male
MH  - Middle Aged
MH  - Neutrophils/metabolism
MH  - Prognosis
MH  - Prospective Studies
MH  - Transcriptome
MH  - Tuberculosis, Meningeal/*immunology/virology
PMC - PMC5388298
OTO - NOTNLM
OT  - HIV
OT  - Tuberculosis meningitis
OT  - inflammasomes
OT  - microarray
OT  - neutrophils
EDAT- 2016/12/10 06:00
MHDA- 2017/05/10 06:00
PMCR- 2016/12/08
CRDT- 2016/12/10 06:00
PHST- 2016/09/03 00:00 [received]
PHST- 2016/11/15 00:00 [accepted]
PHST- 2016/12/10 06:00 [pubmed]
PHST- 2017/05/10 06:00 [medline]
PHST- 2016/12/10 06:00 [entrez]
PHST- 2016/12/08 00:00 [pmc-release]
AID - jiw561 [pii]
AID - 10.1093/infdis/jiw561 [doi]
PST - ppublish
SO  - J Infect Dis. 2017 Mar 1;215(5):677-686. doi: 10.1093/infdis/jiw561.