PMID- 21826013
OWN - NLM
STAT- MEDLINE
DCOM- 20111207
LR  - 20220408
IS  - 1944-7884 (Electronic)
IS  - 1525-4135 (Print)
IS  - 1525-4135 (Linking)
VI  - 58
IP  - 3
DP  - 2011 Nov 1
TI  - Natural killer cell activation distinguishes Mycobacterium tuberculosis-mediated 
      immune reconstitution syndrome from chronic HIV and HIV/MTB coinfection.
PG  - 309-18
LID - 10.1097/QAI.0b013e31822e0d15 [doi]
AB  - BACKGROUND: With increased access to antiretroviral treatment (ART), immune 
      reconstitution inflammatory syndrome (IRIS) in Mycobacterium tuberculosis 
      (MTB)-infected populations remains a clinical challenge. We studied a 
      cross-sectional cohort of HIV-infected subjects in Johannesburg (South Africa) to 
      help define the immune correlates that best distinguish IRIS from ongoing MTB 
      cases. METHODS: We studied HIV+ subjects developing MTB-related unmasking 
      tuberculosis-related immune reconstitution inflammatory syndrome (uTB-IRIS) after 
      ART initiation; control groups were subjects with HIV and 
      HIV/tuberculosis-coinfected subjects with comparable ART treatment. Testing was 
      conducted with whole blood-based 4-color flow cytometry and plasma-based Luminex 
      cytokine assessment. RESULTS: Natural killer cell activation, C-reactive protein, 
      and interleukin 8 serum concentration were significantly higher in uTB-IRIS 
      subjects compared with both control groups. In addition, all MTB-coinfected 
      subjects, independent of clinical presentation, had higher neutrophils and T-cell 
      activation, together with lower lymphocytes, CD4(+) T-cell, and myeloid dendritic 
      cell counts. Using conditional inference tree analysis, we show that elevated 
      natural killer cell activation in combination with lymphocyte count characterizes 
      the immunological profile of uTB-IRIS. CONCLUSION: Our results support a role for 
      innate immune effectors in the immunopathogenesis of unmasking MTB-related IRIS 
      and identify new immune parameters defining this pathology.
FAU - Conradie, Francesca
AU  - Conradie F
AD  - Clinical HIV Research Unit, Department of Medicine, University of the 
      Witwatersrand, Johannesburg, South Africa.
FAU - Foulkes, Andrea S
AU  - Foulkes AS
FAU - Ive, Prudence
AU  - Ive P
FAU - Yin, Xiangfan
AU  - Yin X
FAU - Roussos, Katerina
AU  - Roussos K
FAU - Glencross, Deborah K
AU  - Glencross DK
FAU - Lawrie, Denise
AU  - Lawrie D
FAU - Stevens, Wendy
AU  - Stevens W
FAU - Montaner, Luis J
AU  - Montaner LJ
FAU - Sanne, Ian
AU  - Sanne I
FAU - Azzoni, Livio
AU  - Azzoni L
LA  - eng
GR  - R01 HL107196/HL/NHLBI NIH HHS/United States
GR  - R01 AI069996/AI/NIAID NIH HHS/United States
GR  - P30 CA010815/CA/NCI NIH HHS/United States
GR  - P30 AI045008/AI/NIAID NIH HHS/United States
GR  - P30 CA10815/CA/NCI NIH HHS/United States
GR  - P30 AI 045008/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Acquir Immune Defic Syndr
JT  - Journal of acquired immune deficiency syndromes (1999)
JID - 100892005
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Cytokines)
SB  - IM
MH  - Adult
MH  - Anti-HIV Agents/administration & dosage
MH  - Antiretroviral Therapy, Highly Active/methods
MH  - Cohort Studies
MH  - Cross-Sectional Studies
MH  - Cytokines/metabolism
MH  - Female
MH  - Flow Cytometry
MH  - HIV Infections/complications/*drug therapy/*immunology
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/*diagnosis/*immunology
MH  - Killer Cells, Natural/*immunology
MH  - Male
MH  - Mycobacterium tuberculosis/*immunology
MH  - South Africa
MH  - Tuberculosis/complications/*immunology
PMC - PMC3196770
MID - NIHMS315735
COIS- Conflict of interest Conradie, F.: no conflict of interest declared Foulkes A.S.: 
      no conflict of interest declared Ive, P.: no conflict of interest declared Yin 
      X.: no conflict of interest declared Roussos K.: no conflict of interest declared 
      Glencross D.: no conflict of interest declared Lawrie D.: no conflict of interest 
      declared Stevens W.: no conflict of interest declared Montaner L.J.: no conflict 
      of interest declared Sanne I.: no conflict of interest declared Azzoni L.: no 
      conflict of interest declared
EDAT- 2011/08/10 06:00
MHDA- 2011/12/13 00:00
PMCR- 2011/11/01
CRDT- 2011/08/10 06:00
PHST- 2011/08/10 06:00 [entrez]
PHST- 2011/08/10 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2011/11/01 00:00 [pmc-release]
AID - 10.1097/QAI.0b013e31822e0d15 [doi]
PST - ppublish
SO  - J Acquir Immune Defic Syndr. 2011 Nov 1;58(3):309-18. doi: 
      10.1097/QAI.0b013e31822e0d15.