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Peptidylarginine deiminase 4 concentration,but not PADI4 polymorphisms,is associated with ICU mortality in septic shock patients
Authors:Nara Aline Costa  Ana Lúcia Gut  Paula Schmidt Azevedo  Bertha Furlan Polegato  Eloá Siqueira Magalhães  Larissa Lumi Watanabe Ishikawa  Rita de Cassia Siqueira Bruder  Evelyn Aparecida da Silva  Renan Braga Gonçalves  Suzana Erico Tanni  Marcelo Macedo Rogero  Marina Maintinguer Norde  Natália Baraldi Cunha  Leonardo Antonio Mamede Zornoff  Sergio Alberto Rupp de Paiva  Marcos Ferreira Minicucci
Institution:1. Department of Internal Medicine, Botucatu Medical School, UNESP – Univ Estadual Paulista, Botucatu, Brazil;2. Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, UNESP ‐ Univ. Estadual Paulista, Botucatu, Brazil;3. Nutrition Department, School of Public Health, University of S?o Paulo, S?o Paulo, Brazil
Abstract:The objective of our study was to evaluate the association between peptidylarginine deiminase 4 (PAD4) concentration and its polymorphisms with mortality in patients with septic shock . We prospectively evaluated 175 patients aged over 18 years with septic shock upon intensive care unit (ICU) admission. However, 48 patients were excluded. Thus, 127 patients were enrolled in the study. At the time of the patients’ enrollment, demographic information was recorded. Blood samples were taken within the first 24 hours of the patient's admission to determine serum PAD4 concentrations and its polymorphism PADI4_89 rs11203366], PADI4_94 rs2240340] and PADI4_104 rs1748033]. The mean age was 63.3 ± 15.2 years, 56.7% were male, PAD4 concentration was 4.62 (2.48‐6.20) ng/mL and the ICU mortality rate was 67.7%. The patients who died in the ICU had higher APACHE II and Sequential Organ Failure Assessment (SOFA) scores. In addition, PAD4 concentration was higher in patients who died during ICU stay. However, there were no differences regarding PADI4 polymorphisms and ICU mortality. In the logistic regression models, PAD4 concentrations were associated with ICU mortality when adjusted for APACHE II score and lactate (OR: 1.477; CI 95%: 1.186‐1.839; P < .001), and when adjusted for age, gender and APACHE II score (OR: 1.392; CI 95%: 1.145‐1.692; P < .001). In conclusion, PAD4 concentration, but not PADI4_89, PADI4_94 and PADI4_104 polymorphisms, is associated with ICU mortality in septic shock patients.
Keywords:citrullination  neutrophils extracellular traps  peptidylarginine deiminase 4  sepsis  single nucleotide polymorphisms
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