Combined quantification of procalcitonin and HLA-DR improves sepsis detection in surgical patients

Raquel Almansa,Marta Aragón,Mario Lorenzo-López,Diana Benavides,Silvia Martín,Esther Gómez-Sánchez,César Aldecoa,María Heredia-Rodríguez,Cristina Andrés,Esther Zarca,José Ignacio Gómez-Herreras ,Íñigo López De Cenarruzabeitia ,Luís Muñoz‐Bellvís ,Elisa Sánchez-Barrado ,Alberto Ríos‐Llorente ,Eduardo Tamayo,Agustín Diaz ,Estefanía Gómez-Pesquera ,Jesús Rico-Feijoó ,Cristina Doncel,Alicia Ortega,Marta Martín-Fernández ,J.m Calvo Vecino ,Dolores Calvo,Maria Carmen Esteban‐Velasco ,Juan Beltrán De Heredia ,Carmen González-Sanchez ,Jaime López‐Sánchez ,Luis Mario Vaquero‐Roncero ,Jesús F Bermejo‐Martin

doi:10.1038/s41598-018-30505-7

Abstract

Early recognition of sepsis is a key factor to improve survival to this disease in surgical patients, since it allows prompt control of the infectious source. Combining pro-inflammatory and immunosupression biomarkers could represent a good strategy to improve sepsis detection. Here we evaluated the combination of procalcitonin (PCT) with gene expression levels of HLA-DRA to detect sepsis in a cohort of 154 surgical patients (101 with sepsis and 53 with no infection). HLA-DRA expression was quantified using droplet digital PCR, a next-generation PCR technology. Area under the receiver operating curve analysis (AUROC) showed that the PCT/HLA-DRA ratio outperformed PCT to detect sepsis (AUROC [CI95%], p): PCT: 0.80 [0.73–0.88], <0.001; PCT/HLA-DRA: 0.85 [0.78–0.91], <0.001. In the multivariate analysis, the ratio showed a superior ability to predict sepsis compared to that of PCT (OR [CI 95%], p): PCT/HLA-DRA: 7.66 [1.82–32.29], 0.006; PCT: 4.21 [1.15–15.43] 0.030. Multivariate analysis was confirmed using a new surgical cohort with 74 sepsis patients and 21 controls: PCT/HLA-DRA: 34.86 [1.22–995.08], 0.038; PCT: 5.52 [0.40–75.78], 0.201. In conclusion, the combination of PCT with HLA-DRA is a promising strategy for improving sepsis detection in surgical patients.

Highlights

Recognition of sepsis is a key factor to improve survival to this disease in surgical patients, since it allows prompt control of the infectious source
Recognition and timely treatment largely determine outcome of sepsis[18]. This is important in surgical sepsis, where prompt intervention to control the source of infection is a central element to increase survival[19]
Our study, using a derivation-validation approach, demonstrates for the first time that combining quantification of PCT, a peptide reflecting the host pro-inflammatory response to the infection, with that of HLA-DRA, a transcript reflecting the immunological suppression occurring in sepsis, is a good strategy to enhance chances of detecting this disease in surgical patients

Summary

Introduction

Recognition of sepsis is a key factor to improve survival to this disease in surgical patients, since it allows prompt control of the infectious source. We evaluated the combination of procalcitonin (PCT) with gene expression levels of HLA-DRA to detect sepsis in a cohort of 154 surgical patients (101 with sepsis and 53 with no infection). The combination of PCT with HLA-DRA is a promising strategy for improving sepsis detection in surgical patients. Measuring gene expression levels in blood of HLA-DRA (encoding the non-polymorphic region of the alpha-chain of the HLA-DR molecule) has been proposed as a promising tool for evaluating the degree of immunosupression associated to sepsis[13,14], and significantly predicts mortality in this disease[15]. We employed droplet digital PCR (ddPCR)[16], a next-generation polymerase chain reaction, to quantify gene expression of HLA-DRA in blood

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