OBJECTIVES: To quantify immunological dysfunction in surgical patients with presence/absence of sepsis using a droplet digital polymerase chain reaction (ddPCR) transcriptomic analysis. The study also aims to evaluate this approach for improving identification of sepsis in these patients. BACKGROUND: Immune dysregulation is a central event in sepsis. Quantification of the expression of immunological genes participating in the pathogenesis of sepsis could represent a new avenue to improve its diagnosis. METHODS: Expression of 6 neutrophil protease genes (MMP8, OLFM4, LCN2/NGAL, LTF, PRTN3, MPO) and also of 5 genes involved in the immunological synapse (HLA-DRA, CD40LG, CD3E, CD28, ICOS) was quantified in blood from 101 surgical patients with sepsis, 53 uninfected surgical patients, and 16 blood donors by using ddPCR. Areas under receiver operating characteristic curves (AUROC) and multivariate regression analysis were employed to test individual genes and gene ratios to identify sepsis, in comparison with procalcitonin. RESULTS: Sepsis-induced overexpression of neutrophil protease genes and depressed expression of immunological synapse genes. MMP8/HLA-DRA, LCN2/HLA-DRA outperformed procalcitonin in differentiating between patients with sepsis and surgical controls in the AUROC analysis: LCN2/HLA-DRA: 0.90 (0.85-0.96), MMP8/HLA-DRA: 0.89 (0.84-0.95), procalcitonin: 0.80 (0.73-0.88) (AUROC, confidence interval 95%), and also in the multivariate analysis: LCN2/HLA-DRA: 8.57 (2.25-32.62); MMP8/HLA-DRA: 8.03 (2.10-30.76), procalcitonin: 4.20 (1.15-15.43) [odds ratio (confidence interval 95%)]. Gene expression levels of HLA-DRA were an independent marker of hospital mortality. CONCLUSIONS: Quantifying the transcriptomic ratios MMP8/HLA-DRA, LCN2/HLA-DRA by ddPCR is a promising approach to improve sepsis diagnosis in surgical patients.
OBJECTIVES: To quantify immunological dysfunction in surgical patients with presence/absence of sepsis using a droplet digital polymerase chain reaction (ddPCR) transcriptomic analysis. The study also aims to evaluate this approach for improving identification of sepsis in these patients. BACKGROUND: Immune dysregulation is a central event in sepsis. Quantification of the expression of immunological genes participating in the pathogenesis of sepsis could represent a new avenue to improve its diagnosis. METHODS: Expression of 6 neutrophil protease genes (MMP8, OLFM4, LCN2/NGAL, LTF, PRTN3, MPO) and also of 5 genes involved in the immunological synapse (HLA-DRA, CD40LG, CD3E, CD28, ICOS) was quantified in blood from 101 surgical patients with sepsis, 53 uninfected surgical patients, and 16 blood donors by using ddPCR. Areas under receiver operating characteristic curves (AUROC) and multivariate regression analysis were employed to test individual genes and gene ratios to identify sepsis, in comparison with procalcitonin. RESULTS:Sepsis-induced overexpression of neutrophil protease genes and depressed expression of immunological synapse genes. MMP8/HLA-DRA, LCN2/HLA-DRA outperformed procalcitonin in differentiating between patients with sepsis and surgical controls in the AUROC analysis: LCN2/HLA-DRA: 0.90 (0.85-0.96), MMP8/HLA-DRA: 0.89 (0.84-0.95), procalcitonin: 0.80 (0.73-0.88) (AUROC, confidence interval 95%), and also in the multivariate analysis: LCN2/HLA-DRA: 8.57 (2.25-32.62); MMP8/HLA-DRA: 8.03 (2.10-30.76), procalcitonin: 4.20 (1.15-15.43) [odds ratio (confidence interval 95%)]. Gene expression levels of HLA-DRA were an independent marker of hospital mortality. CONCLUSIONS: Quantifying the transcriptomic ratios MMP8/HLA-DRA, LCN2/HLA-DRA by ddPCR is a promising approach to improve sepsis diagnosis in surgical patients.
Authors: Raquel Almansa; Leonor Nogales; Marta Martín-Fernández; Montse Batlle; Esther Villareal; Lucia Rico; Alicia Ortega; Guillermo López-Campos; David Andaluz-Ojeda; Paula Ramírez; Lorenzo Socias; Luis Tamayo; Jordi Vallés; Jesús F Bermejo-Martín; Ignacio Martín-Loeches Journal: Ann Transl Med Date: 2018-11
Authors: Kirsten N Kangelaris; Regina Clemens; Xiaohui Fang; Alejandra Jauregui; Tom Liu; Kathryn Vessel; Thomas Deiss; Pratik Sinha; Aleksandra Leligdowicz; Kathleen D Liu; Hanjing Zhuo; Matthew N Alder; Hector R Wong; Carolyn S Calfee; Clifford Lowell; Michael A Matthay Journal: Am J Physiol Lung Cell Mol Physiol Date: 2020-12-23 Impact factor: 5.464
Authors: Jesus F Bermejo-Martin; Catia Cilloniz; Raul Mendez; Raquel Almansa; Albert Gabarrus; Adrian Ceccato; Antoni Torres; Rosario Menendez Journal: EBioMedicine Date: 2017-09-21 Impact factor: 8.143
Authors: M Martin-Fernandez; L M Vaquero-Roncero; R Almansa; E Gómez-Sánchez; S Martín; E Tamayo; M C Esteban-Velasco; P Ruiz-Granado; M Aragón; D Calvo; J Rico-Feijoo; A Ortega; E Gómez-Pesquera; M Lorenzo-López; J López; C Doncel; C González-Sanchez; D Álvarez; E Zarca; A Ríos-Llorente; A Diaz-Alvarez; E Sanchez-Barrado; D Andaluz-Ojeda; J M Calvo-Vecino; L Muñoz-Bellvís; J I Gomez-Herreras; C Abad-Molina; J F Bermejo-Martin; C Aldecoa; M Heredia-Rodríguez Journal: BJS Open Date: 2020-02-19
Authors: Raquel Almansa; Silvia Martín; Marta Martin-Fernandez; María Heredia-Rodríguez; Esther Gómez-Sánchez; Marta Aragón; Cristina Andrés; Dolores Calvo; Jesus Rico-Feijoo; Maria Carmen Esteban-Velasco; Luis Mario Vaquero-Roncero; Alicia Ortega; Estefania Gómez-Pesquera; Mario Lorenzo-López; Iñigo López de Cenarruzabeitia; Diana Benavides; Jaime López-Sanchez; Cristina Doncel; Carmen González-Sanchez; Esther Zarca; Alberto Ríos-Llorente; Agustín Diaz; Elisa Sanchez-Barrado; Juan Beltran de Heredia; Jose Maria Calvo-Vecino; Luis Muñoz-Bellvís; Jose Ignacio Gomez-Herreras; César Aldecoa; Eduardo Tamayo; Jesus F Bermejo-Martin Journal: Sci Rep Date: 2018-08-10 Impact factor: 4.379
Authors: Pedro Martínez-Paz; Marta Aragón-Camino; Esther Gómez-Sánchez; Mario Lorenzo-López; Estefanía Gómez-Pesquera; Rocío López-Herrero; Belén Sánchez-Quirós; Olga de la Varga; Álvaro Tamayo-Velasco; Christian Ortega-Loubon; Emilio García-Morán; Hugo Gonzalo-Benito; María Heredia-Rodríguez; Eduardo Tamayo Journal: J Clin Med Date: 2020-04-28 Impact factor: 4.241