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TIM-3 Genetic Variants Are Associated with Altered Clinical Outcome and Susceptibility to Gram-Positive Infections in Patients with Sepsis

Background: Previous studies have reported the fundamental role of immunoregulatory proteins in the clinical phenotype and outcome of sepsis. This study investigated two functional single nucleotide polymorphisms (SNPs) of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), which ha...

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Autores principales: Mewes, Caspar, Alexander, Tessa, Büttner, Benedikt, Hinz, José, Alpert, Ayelet, Popov, Aron-F., Ghadimi, Michael, Beißbarth, Tim, Tzvetkov, Mladen, Grade, Marian, Quintel, Michael, Bergmann, Ingo, Mansur, Ashham
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664272/
https://www.ncbi.nlm.nih.gov/pubmed/33171904
http://dx.doi.org/10.3390/ijms21218318
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author Mewes, Caspar
Alexander, Tessa
Büttner, Benedikt
Hinz, José
Alpert, Ayelet
Popov, Aron-F.
Ghadimi, Michael
Beißbarth, Tim
Tzvetkov, Mladen
Grade, Marian
Quintel, Michael
Bergmann, Ingo
Mansur, Ashham
author_facet Mewes, Caspar
Alexander, Tessa
Büttner, Benedikt
Hinz, José
Alpert, Ayelet
Popov, Aron-F.
Ghadimi, Michael
Beißbarth, Tim
Tzvetkov, Mladen
Grade, Marian
Quintel, Michael
Bergmann, Ingo
Mansur, Ashham
author_sort Mewes, Caspar
collection PubMed
description Background: Previous studies have reported the fundamental role of immunoregulatory proteins in the clinical phenotype and outcome of sepsis. This study investigated two functional single nucleotide polymorphisms (SNPs) of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), which has a negative stimulatory function in the T cell immune response. Methods: Patients with sepsis (n = 712) were prospectively enrolled from three intensive care units (ICUs) at the University Medical Center Goettingen since 2012. All patients were genotyped for the TIM-3 SNPs rs1036199 and rs10515746. The primary outcome was 28-day mortality. Disease severity and microbiological findings were secondary endpoints. Results: Kaplan–Meier survival analysis demonstrated a significantly lower 28-day mortality for TIM-3 rs1036199 AA homozygous patients compared to C-allele carriers (18% vs. 27%, p = 0.0099) and TIM-3 rs10515746 CC homozygous patients compared to A-allele carriers (18% vs. 26%, p = 0.0202). The TIM-3 rs1036199 AA genotype and rs10515746 CC genotype remained significant predictors for 28-day mortality in the multivariate Cox regression analysis after adjustment for relevant confounders (adjusted hazard ratios: 0.67 and 0.70). Additionally, patients carrying the rs1036199 AA genotype presented more Gram-positive and Staphylococcus epidermidis infections, and rs10515746 CC homozygotes presented more Staphylococcus epidermidis infections. Conclusion: The studied TIM-3 genetic variants are associated with altered 28-day mortality and susceptibility to Gram-positive infections in sepsis.
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spelling pubmed-76642722020-11-14 TIM-3 Genetic Variants Are Associated with Altered Clinical Outcome and Susceptibility to Gram-Positive Infections in Patients with Sepsis Mewes, Caspar Alexander, Tessa Büttner, Benedikt Hinz, José Alpert, Ayelet Popov, Aron-F. Ghadimi, Michael Beißbarth, Tim Tzvetkov, Mladen Grade, Marian Quintel, Michael Bergmann, Ingo Mansur, Ashham Int J Mol Sci Article Background: Previous studies have reported the fundamental role of immunoregulatory proteins in the clinical phenotype and outcome of sepsis. This study investigated two functional single nucleotide polymorphisms (SNPs) of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), which has a negative stimulatory function in the T cell immune response. Methods: Patients with sepsis (n = 712) were prospectively enrolled from three intensive care units (ICUs) at the University Medical Center Goettingen since 2012. All patients were genotyped for the TIM-3 SNPs rs1036199 and rs10515746. The primary outcome was 28-day mortality. Disease severity and microbiological findings were secondary endpoints. Results: Kaplan–Meier survival analysis demonstrated a significantly lower 28-day mortality for TIM-3 rs1036199 AA homozygous patients compared to C-allele carriers (18% vs. 27%, p = 0.0099) and TIM-3 rs10515746 CC homozygous patients compared to A-allele carriers (18% vs. 26%, p = 0.0202). The TIM-3 rs1036199 AA genotype and rs10515746 CC genotype remained significant predictors for 28-day mortality in the multivariate Cox regression analysis after adjustment for relevant confounders (adjusted hazard ratios: 0.67 and 0.70). Additionally, patients carrying the rs1036199 AA genotype presented more Gram-positive and Staphylococcus epidermidis infections, and rs10515746 CC homozygotes presented more Staphylococcus epidermidis infections. Conclusion: The studied TIM-3 genetic variants are associated with altered 28-day mortality and susceptibility to Gram-positive infections in sepsis. MDPI 2020-11-06 /pmc/articles/PMC7664272/ /pubmed/33171904 http://dx.doi.org/10.3390/ijms21218318 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mewes, Caspar
Alexander, Tessa
Büttner, Benedikt
Hinz, José
Alpert, Ayelet
Popov, Aron-F.
Ghadimi, Michael
Beißbarth, Tim
Tzvetkov, Mladen
Grade, Marian
Quintel, Michael
Bergmann, Ingo
Mansur, Ashham
TIM-3 Genetic Variants Are Associated with Altered Clinical Outcome and Susceptibility to Gram-Positive Infections in Patients with Sepsis
title TIM-3 Genetic Variants Are Associated with Altered Clinical Outcome and Susceptibility to Gram-Positive Infections in Patients with Sepsis
title_full TIM-3 Genetic Variants Are Associated with Altered Clinical Outcome and Susceptibility to Gram-Positive Infections in Patients with Sepsis
title_fullStr TIM-3 Genetic Variants Are Associated with Altered Clinical Outcome and Susceptibility to Gram-Positive Infections in Patients with Sepsis
title_full_unstemmed TIM-3 Genetic Variants Are Associated with Altered Clinical Outcome and Susceptibility to Gram-Positive Infections in Patients with Sepsis
title_short TIM-3 Genetic Variants Are Associated with Altered Clinical Outcome and Susceptibility to Gram-Positive Infections in Patients with Sepsis
title_sort tim-3 genetic variants are associated with altered clinical outcome and susceptibility to gram-positive infections in patients with sepsis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664272/
https://www.ncbi.nlm.nih.gov/pubmed/33171904
http://dx.doi.org/10.3390/ijms21218318
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