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Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study

(1) Background: Sepsis is a leading cause of death and a global public health problem. Accordingly, deciphering the underlying molecular mechanisms of this disease and the determinants of its morbidity and mortality is pivotal. This study examined the effect of the rs951818 SNP of the negative costi...

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Autores principales: Mewes, Caspar, Alexander, Tessa, Büttner, Benedikt, Hinz, José, Alpert, Ayelet, Popov, Aron-F., Beißbarth, Tim, Tzvetkov, Mladen, Grade, Marian, Quintel, Michael, Bergmann, Ingo, Mansur, Ashham
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621793/
https://www.ncbi.nlm.nih.gov/pubmed/34830585
http://dx.doi.org/10.3390/jcm10225302
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author Mewes, Caspar
Alexander, Tessa
Büttner, Benedikt
Hinz, José
Alpert, Ayelet
Popov, Aron-F.
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.
Beißbarth, Tim
Tzvetkov, Mladen
Grade, Marian
Quintel, Michael
Bergmann, Ingo
Mansur, Ashham
author_sort Mewes, Caspar
collection PubMed
description (1) Background: Sepsis is a leading cause of death and a global public health problem. Accordingly, deciphering the underlying molecular mechanisms of this disease and the determinants of its morbidity and mortality is pivotal. This study examined the effect of the rs951818 SNP of the negative costimulatory lymphocyte-activation gene 3 (LAG-3) on sepsis mortality and disease severity. (2) Methods: 707 consecutive patients with sepsis were prospectively enrolled into the present study from three surgical ICUs at University Medical Center Goettingen. Both 28- and 90-day mortality were analyzed as the primary outcome, while parameters of disease severity served as secondary endpoints. (3) Results: In the Kaplan–Meier analysis LAG-3 rs951818 AA-homozygote patients showed a significantly lower 28-day mortality (17.3%) compared to carriers of the C-allele (23.7%, p = 0.0476). In addition, these patients more often received invasive mechanical ventilation (96%) during the course of disease than C-allele carriers (92%, p = 0.0466). (4) Conclusions: Genetic profiling of LAG-3 genetic variants alone or in combination with other genetic biomarkers may represent a promising approach for risk stratification of patients with sepsis. Patient-individual therapeutic targeting of immune checkpoints, such as LAG-3, may be a future component of sepsis therapy. Further detailed investigations in clinically relevant sepsis models are necessary.
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spelling pubmed-86217932021-11-27 Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study Mewes, Caspar Alexander, Tessa Büttner, Benedikt Hinz, José Alpert, Ayelet Popov, Aron-F. Beißbarth, Tim Tzvetkov, Mladen Grade, Marian Quintel, Michael Bergmann, Ingo Mansur, Ashham J Clin Med Article (1) Background: Sepsis is a leading cause of death and a global public health problem. Accordingly, deciphering the underlying molecular mechanisms of this disease and the determinants of its morbidity and mortality is pivotal. This study examined the effect of the rs951818 SNP of the negative costimulatory lymphocyte-activation gene 3 (LAG-3) on sepsis mortality and disease severity. (2) Methods: 707 consecutive patients with sepsis were prospectively enrolled into the present study from three surgical ICUs at University Medical Center Goettingen. Both 28- and 90-day mortality were analyzed as the primary outcome, while parameters of disease severity served as secondary endpoints. (3) Results: In the Kaplan–Meier analysis LAG-3 rs951818 AA-homozygote patients showed a significantly lower 28-day mortality (17.3%) compared to carriers of the C-allele (23.7%, p = 0.0476). In addition, these patients more often received invasive mechanical ventilation (96%) during the course of disease than C-allele carriers (92%, p = 0.0466). (4) Conclusions: Genetic profiling of LAG-3 genetic variants alone or in combination with other genetic biomarkers may represent a promising approach for risk stratification of patients with sepsis. Patient-individual therapeutic targeting of immune checkpoints, such as LAG-3, may be a future component of sepsis therapy. Further detailed investigations in clinically relevant sepsis models are necessary. MDPI 2021-11-15 /pmc/articles/PMC8621793/ /pubmed/34830585 http://dx.doi.org/10.3390/jcm10225302 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mewes, Caspar
Alexander, Tessa
Büttner, Benedikt
Hinz, José
Alpert, Ayelet
Popov, Aron-F.
Beißbarth, Tim
Tzvetkov, Mladen
Grade, Marian
Quintel, Michael
Bergmann, Ingo
Mansur, Ashham
Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study
title Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study
title_full Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study
title_fullStr Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study
title_full_unstemmed Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study
title_short Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study
title_sort effect of the lymphocyte activation gene 3 polymorphism rs951818 on mortality and disease progression in patients with sepsis—a prospective genetic association study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621793/
https://www.ncbi.nlm.nih.gov/pubmed/34830585
http://dx.doi.org/10.3390/jcm10225302
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