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

  • 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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Author: Caspar Mewes, Tessa Alexander, Benedikt Büttner, José Hinz, Ayelet Alpert, Aron-F. Popov, Michael Ghadimi, Tim Beißbarth, Mladen Tzvetkov, Marian Grade, Michael Quintel, Ingo Bergmann, Ashham Mansur
Parent Title (English):International Journal of Molecular Sciences
Place of publication:Basel
Document Type:Article
Date of first Publication:2020/11/06
Release Date:2022/11/22
Tag:Gram-positive infections; TIM-3; mortality; predictor; sepsis; single nucleotide polymorphism (SNP)
GND Keyword:-
Page Number:16
Faculties:Universitätsmedizin / Institut für Pharmakologie
Licence (German):License LogoCreative Commons - Namensnennung