Mass spectrometry-based methods for the detection of circulating histones h3 and h2b in plasma from sepsis or septic shock (SS) patients

A septic shock, circulatory group technology, applied in the field of disease diagnosis/prognosis, medicine, can solve the problems of reproducibility difference, high error range, erroneous results, etc.

Pending Publication Date: 2019-10-11
CENT DE INVESTIGACION BIOMEDICA & RED CIBER ISCIII +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Immunoassays (IAs) for the detection of free histones circulating in plasma have been used previously, but results obtained by IA showed low reproducibility, high error margins and low sensitivity
Furthermore, semi-quantitative IA exhibits many drawbacks, for example, poor agreement between assays, differences in reproducibility when using different kits from the manufacturer using different proprietary antibodies (recognizing different epitopes in each assay), and variable cross-reactivity
In addition, various interferences can occur in IA, including the presence of anti-reagent antibodies and endogenous autoantibodies in the tested biological sample, which can produce erroneous results and cause clinical side effects

Method used

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  • Mass spectrometry-based methods for the detection of circulating histones h3 and h2b in plasma from sepsis or septic shock (SS) patients
  • Mass spectrometry-based methods for the detection of circulating histones h3 and h2b in plasma from sepsis or septic shock (SS) patients
  • Mass spectrometry-based methods for the detection of circulating histones h3 and h2b in plasma from sepsis or septic shock (SS) patients

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0087] Example 1. Results

[0088] General description of the queue

[0089] A total of 17 patients who were clinically diagnosed with SS on admission to the medical ICU were analyzed. The median age was 67 years (range, 37 to 85 years), and male patients accounted for 67% of cases. The median APACHE II score was 25 (14-44), and the median SOFA score was 10 (3 to 19).

[0090] Table 1 shows the clinical characteristics of the patients.

[0091]

[0092]

[0093]

[0094] SD = standard deviation, APACHE = acute physiology and chronic health assessment, SOFA = sequential organ failure assessment, SSTI = skin and soft tissue infection, MDR = multidrug resistant organisms, RRT = renal replacement therapy, ICU = intensive care unit, LOS = length of residence CRP = C-reactive protein, PaO2 / FiO2 ratio = partial pressure of arterial oxygen to fraction of inspired oxygen

[0095] a MDR (extended-spectrum beta-lactamase-producing Escherichia coli and Meticilin-resistant...

Embodiment 2

[0116] Example 2. Differentiated diagnosis

[0117] A total of 40 samples were analyzed and the following group distribution was included in the study: 11 controls selected in the ICU without infectious conditions (non-septic ICU control patients), 11 controls selected from the general healthy population, 8 septic cases of septic shock and 10 cases of septic shock.

[0118] For histone H2B, the average levels found in the 40 plasmas were as follows (Table 2):

[0119] Group [H2B]ng / mL (CI 95%) ICU control group 132.63(92.68-172.59) common control group 108.87(84.23-133.50) sepsis 219.63(162.05-277.21) septic shock 1305.32(587.42-2023.23)

[0120] Figure 5 The results are shown in , where the levels of circulating histone H2B in plasma from controls (ICU and general population), sepsis and septic shock patients are shown. Box-and-whisker plots represent H2B levels in the four groups. Boxes indicate interquartile ranges, horizontal ...

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Abstract

The present invention proposes a novel method for the detection of circulating histones H3 and H2B in plasma from sepsis or septic shock (SS) patients, based on mass spectrometry-based methods, in particular based on multiple reaction monitoring targeted mass spectrometry (MRM-MS). Such methods allow quantification of histones using an internal standard and show strong specificity and sensitivityvalues.

Description

technical field [0001] The present invention relates to the field of medicine, in particular to the field of disease diagnosis / prognosis based on detection of plasma biomarkers by using mass spectrometry-based methods. More specifically, the present invention relates to a mass spectrometry-based method for the detection of circulating histone H3 and H2B in the plasma of patients suspected of having sepsis or septic shock for those patients undergoing sepsis or septic shock diagnosis / prognosis. Background technique [0002] Sepsis is defined as a systemic host inflammatory response to a serious, life-threatening infection with biochemical abnormalities and organ dysfunction. This is a major healthcare problem that affects millions of people around the world every year. The incidence of sepsis is increasing due to population aging, immunosenescence, and resulting compromised immunity. Additionally, sepsis is the most common cause of death in most intensive care units (ICUs)...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68
CPCG01N33/6848G01N33/6893G01N2800/26G01N2800/56
Inventor 何塞·路易斯·加西亚·吉梅内斯卡洛斯·罗马·马特奥费德里科·V·帕拉德·卡拉塔尤德
Owner CENT DE INVESTIGACION BIOMEDICA & RED CIBER ISCIII
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