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Serum proteome profiles in patients treated with targeted temperature management after out-of-hospital cardiac arrest

Lileikyte, Gabriele LU orcid ; Bakochi, Anahita LU orcid ; Ali, Ashfaq LU orcid ; Moseby-Knappe, Marion LU ; Cronberg, Tobias LU ; Friberg, Hans LU ; Lilja, Gisela LU ; Levin, Helena LU ; Årman, Filip LU and Kjellström, Sven LU , et al. (2023) In Intensive Care Medicine Experimental 11(1).
Abstract

BACKGROUND: Definition of temporal serum proteome profiles after out-of-hospital cardiac arrest may identify biological processes associated with severe hypoxia-ischaemia and reperfusion. It may further explore intervention effects for new mechanistic insights, identify candidate prognostic protein biomarkers and potential therapeutic targets. This pilot study aimed to investigate serum proteome profiles from unconscious patients admitted to hospital after out-of-hospital cardiac arrest according to temperature treatment and neurological outcome.

METHODS: Serum samples at 24, 48, and 72 h after cardiac arrest at three centres included in the Target Temperature Management after out-of-hospital cardiac arrest trial underwent... (More)

BACKGROUND: Definition of temporal serum proteome profiles after out-of-hospital cardiac arrest may identify biological processes associated with severe hypoxia-ischaemia and reperfusion. It may further explore intervention effects for new mechanistic insights, identify candidate prognostic protein biomarkers and potential therapeutic targets. This pilot study aimed to investigate serum proteome profiles from unconscious patients admitted to hospital after out-of-hospital cardiac arrest according to temperature treatment and neurological outcome.

METHODS: Serum samples at 24, 48, and 72 h after cardiac arrest at three centres included in the Target Temperature Management after out-of-hospital cardiac arrest trial underwent data-independent acquisition mass spectrometry analysis (DIA-MS) to find changes in serum protein concentrations associated with neurological outcome at 6-month follow-up and targeted temperature management (TTM) at 33 °C as compared to 36 °C. Neurological outcome was defined according to Cerebral Performance Category (CPC) scale as "good" (CPC 1-2, good cerebral performance or moderate disability) or "poor" (CPC 3-5, severe disability, unresponsive wakefulness syndrome, or death).

RESULTS: Of 78 included patients [mean age 66 ± 12 years, 62 (80.0%) male], 37 (47.4%) were randomised to TTM at 36 °C. Six-month outcome was poor in 47 (60.3%) patients. The DIA-MS analysis identified and quantified 403 unique human proteins. Differential protein abundance testing comparing poor to good outcome showed 19 elevated proteins in patients with poor outcome (log
2-fold change (FC) range 0.28-1.17) and 16 reduced proteins (log
2(FC) between - 0.22 and - 0.68), involved in inflammatory/immune responses and apoptotic signalling pathways for poor outcome and proteolysis for good outcome. Analysis according to level of TTM showed a significant protein abundance difference for six proteins [five elevated proteins in TTM 36 °C (log
2(FC) between 0.33 and 0.88), one reduced protein (log
2(FC) - 0.6)] mainly involved in inflammatory/immune responses only at 48 h after cardiac arrest.

CONCLUSIONS: Serum proteome profiling revealed an increase in inflammatory/immune responses and apoptosis in patients with poor outcome. In patients with good outcome, an increase in proteolysis was observed, whereas TTM-level only had a modest effect on the proteome profiles. Further validation of the differentially abundant proteins in response to neurological outcome is necessary to validate novel biomarker candidates that may predict prognosis after cardiac arrest.

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publishing date
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Contribution to journal
publication status
published
subject
in
Intensive Care Medicine Experimental
volume
11
issue
1
article number
43
publisher
Springer
external identifiers
  • scopus:85165272345
  • pmid:37455296
ISSN
2197-425X
DOI
10.1186/s40635-023-00528-0
language
English
LU publication?
yes
id
c1f830ab-ceca-452b-89bf-937539e00d94
date added to LUP
2023-07-19 09:05:19
date last changed
2024-06-29 05:56:52
@article{c1f830ab-ceca-452b-89bf-937539e00d94,
  abstract     = {{<p>BACKGROUND: Definition of temporal serum proteome profiles after out-of-hospital cardiac arrest may identify biological processes associated with severe hypoxia-ischaemia and reperfusion. It may further explore intervention effects for new mechanistic insights, identify candidate prognostic protein biomarkers and potential therapeutic targets. This pilot study aimed to investigate serum proteome profiles from unconscious patients admitted to hospital after out-of-hospital cardiac arrest according to temperature treatment and neurological outcome.</p><p>METHODS: Serum samples at 24, 48, and 72 h after cardiac arrest at three centres included in the Target Temperature Management after out-of-hospital cardiac arrest trial underwent data-independent acquisition mass spectrometry analysis (DIA-MS) to find changes in serum protein concentrations associated with neurological outcome at 6-month follow-up and targeted temperature management (TTM) at 33 °C as compared to 36 °C. Neurological outcome was defined according to Cerebral Performance Category (CPC) scale as "good" (CPC 1-2, good cerebral performance or moderate disability) or "poor" (CPC 3-5, severe disability, unresponsive wakefulness syndrome, or death).</p><p>RESULTS: Of 78 included patients [mean age 66 ± 12 years, 62 (80.0%) male], 37 (47.4%) were randomised to TTM at 36 °C. Six-month outcome was poor in 47 (60.3%) patients. The DIA-MS analysis identified and quantified 403 unique human proteins. Differential protein abundance testing comparing poor to good outcome showed 19 elevated proteins in patients with poor outcome (log<br>
 2-fold change (FC) range 0.28-1.17) and 16 reduced proteins (log<br>
 2(FC) between - 0.22 and - 0.68), involved in inflammatory/immune responses and apoptotic signalling pathways for poor outcome and proteolysis for good outcome. Analysis according to level of TTM showed a significant protein abundance difference for six proteins [five elevated proteins in TTM 36 °C (log<br>
 2(FC) between 0.33 and 0.88), one reduced protein (log<br>
 2(FC) - 0.6)] mainly involved in inflammatory/immune responses only at 48 h after cardiac arrest.<br>
 </p><p>CONCLUSIONS: Serum proteome profiling revealed an increase in inflammatory/immune responses and apoptosis in patients with poor outcome. In patients with good outcome, an increase in proteolysis was observed, whereas TTM-level only had a modest effect on the proteome profiles. Further validation of the differentially abundant proteins in response to neurological outcome is necessary to validate novel biomarker candidates that may predict prognosis after cardiac arrest.</p>}},
  author       = {{Lileikyte, Gabriele and Bakochi, Anahita and Ali, Ashfaq and Moseby-Knappe, Marion and Cronberg, Tobias and Friberg, Hans and Lilja, Gisela and Levin, Helena and Årman, Filip and Kjellström, Sven and Dankiewicz, Josef and Hassager, Christian and Malmström, Johan and Nielsen, Niklas}},
  issn         = {{2197-425X}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{1}},
  publisher    = {{Springer}},
  series       = {{Intensive Care Medicine Experimental}},
  title        = {{Serum proteome profiles in patients treated with targeted temperature management after out-of-hospital cardiac arrest}},
  url          = {{http://dx.doi.org/10.1186/s40635-023-00528-0}},
  doi          = {{10.1186/s40635-023-00528-0}},
  volume       = {{11}},
  year         = {{2023}},
}