CN117288961A - Application of CRISP3 protein in preparation of biomarker for early warning of sepsis - Google Patents
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Abstract
The invention relates to application of CRISP3 protein in preparation of a biomarker for early warning of sepsis, and the invention uses CRISP3 protein in blood plasma or serum as the biomarker for early warning of sepsis occurrence risk of critically ill patients, so as to solve the problem of insufficient clinical application in early warning methods of sepsis in the prior art.
Description
Technical Field
The invention relates to the field of medicine, in particular to application of CRISP3 protein in preparation of biomarkers for early warning of sepsis.
Background
Sepsis (sepsis) is a life threatening multiple organ dysfunction caused by a host's immune dysfunction to infection. A large number of researches prove that the early accurate treatment can obviously reduce the incidence rate of patients with sepsis and improve the prognosis of the patients with sepsis. Among them, microbial culture is a gold standard for sepsis diagnosis, but microbial culture takes 3 to 5 days mostly, with high false negative results.
Therefore, new sepsis therapeutic targets and biomarkers are developed, early warning is carried out on patients with high sepsis risk, and the method plays an important role in reducing the incidence rate and the death rate of sepsis.
The ideal sepsis biological markers should have high efficiency, can rapidly identify the infection of potential pathogenic bacteria and accurately reflect the prognosis of anti-infection curative effect. The most widely used clinical indicators for monitoring sepsis include: c-reactive protein (CRP), procalcitonin (PCT) and interleukin 6 (IL-6), but its sensitivity and specificity have been underscored. PCT, CRP often appear elevated to varying degrees at the end of surgery, autoimmune disease and other underlying diseases, with low specificity; PCT and CRP can only reflect the extent of systemic inflammatory response of patients at the time of detection, and the results vary greatly with the detection time window; IL-6 has short residence time in blood, is difficult to accurately grasp proper detection time, and has limited influence on the outcome early warning of patients with sepsis.
CRISP3 belongs to the family of Cysteine-rich secreted proteins (CRISP-rich secretory protein), which are mainly distributed in the cytoplasm and the cytosol, and are widely found in human tissue fluids such as saliva, blood, seminal plasma, uterine fluid. Current studies indicate that CRISP3 is primarily localized and expressed in neutrophils and thymocytes, which are the first line of defense against invading pathogens, and CRISP3 released into inflammatory sites may play a role in protecting against pathogen spread. Meanwhile, studies have also found that CRISP3 is homologous to an antipathogenic protein induced by infection in plants, further supporting the notion that CRISP3 may act as an immunomodulator. In addition, studies have found that CRISP3 mRNA is up-regulated in immunocompromised mouse models of infection with hepatitis c virus, CRISP3 limits replication of hepatitis c virus in the early stages of infection, demonstrating that CRISP3 has some immune resistance to infection with hepatitis c virus. Thus, CRISP3 is currently considered to be an immunoreactive molecule. No studies have yet demonstrated the early warning effect of plasma or serum CRISP3 proteins in sepsis.
Disclosure of Invention
In view of the above, the invention aims to provide an application of CRISP3 protein in preparing a biomarker for early warning of sepsis, and the application uses CRISP3 protein in blood plasma or blood serum as the biomarker for early warning of sepsis occurrence risk of critically ill patients, so as to solve the problem of insufficient clinical application in early warning methods of sepsis in the prior art.
The technical scheme of the invention is as follows:
use of CRISP3 protein in the preparation of a marker for early warning of sepsis.
The marker is CRISP3 protein in serum, plasma or blood.
The CRISP3 protein expression level in the plasma or serum of patients with sepsis is significantly increased.
Use of CRISP3 protein in the manufacture of a diagnostic reagent for assessing the efficacy of a sepsis treatment.
The diagnostic agent is CRISP3 protein in blood, serum or plasma.
The CRISP3 protein expression level is positively correlated with organ dysfunction severity.
In some embodiments of the invention, the amount of CRISP3 protein expression in the body fluid sample (serum, plasma or blood) is significantly increased in sepsis in critically ill patients.
In some embodiments of the invention, the amount of CRISP3 protein expression is detected using an ELISA double antibody sandwich method (ELISA kit).
Experiments prove that the CRISP3 protein in the blood plasma or serum is used as a biomarker, and the method has important help for improving the early stage and the accuracy of the early warning of sepsis. In one aspect, the invention provides that CRISP3 protein can be used as an early warning indicator of sepsis; in another aspect, the invention provides that CRISP3 protein can be used as an indicator for assessing sepsis severity.
Drawings
FIG. 1 shows a significant increase in CRISP3 protein content in plasma of patients with sepsis (p < 0.05) compared to non-sepsis patients, wherein FIGS. 1a and 1b show significant increases in CRISP3 protein content in plasma of patients with sepsis in a first group of humans and a second group of humans, respectively;
FIG. 2 shows that the CRISP3 protein content in the plasma of a patient is positively correlated with the degree of organ dysfunction (SOFA, APACHII), wherein FIGS. 2a, 2b and 2c, 2d show that the CRISP3 protein content in the plasma of a first group of people and a second group of people, respectively, is positively correlated with the degree of organ dysfunction;
fig. 3 is a schematic diagram showing the early warning effect of ROC curve comparison analysis PCT, CRP and CRISP3 in sepsis according to the embodiment of the present invention, wherein fig. 3a and fig. 3b show schematic diagrams showing the early warning effect of ROC curve comparison analysis PCT, CRP and CRISP3 in sepsis of a first group of people and a second group of people, respectively.
Detailed Description
The present invention will be further explained below with reference to specific examples and drawings for more specific explanation of the invention. The examples are provided solely for the purpose of facilitating understanding of the other advantages and capabilities of the present invention and are not intended to limit the present invention in any way. The details in the description may be modified or varied from different points of view and applications without departing from the requirements of the invention. Experimental methods for which specific conditions are not noted in the examples are conventional methods and conventional conditions well known in the art or according to the conditions suggested by the manufacturer.
Example 1 detection of CRISP3 protein in blood of critically ill patients and changes in expression in sepsis patients
Plasma samples of 54 cases (Xinjiang military general hospital, first group of people) and 166 cases (Chinese people's liberation army special medical center, second group of people) of severely wounded patients within 24 hours after two people are admitted are collected respectively, CRISP3 protein expression level is detected by ELISA kit (purchased from Biorbyt, germany), specific operation steps of ELISA test are referred to the kit instruction, and CRISP3 protein expression level in plasma of sepsis patients and non-sepsis patients in the two groups is analyzed. The differences between the two groups were either independent sample t-test or nonparametric test.
The results show that: plasma CRISP3 protein levels were significantly higher in the study population of 54 patients than in non-sepsis patients (1.305±0.535ng/mL vs.0.743±0.270ng/mL p < 0.001) (fig. 1 a). Meanwhile, plasma CRISP3 protein levels were significantly higher in the study population of 166 patients than in non-sepsis patients (1.542 ±1.075ng/mL vs.0.696±0.509ng/mL, p < 0.001) (fig. 1 b).
Example 2 analysis of correlation of plasma CRISP3 protein levels with severity of organ dysfunction
In the study population of 54 and 166 severely trauma patients, SOFA, APACHEII was used to evaluate the organ dysfunction levels of the patients, and the correlation of plasma CRISP3 protein and organ dysfunction severity in both populations was analyzed. The correlation analysis uses Pearson correlation analysis.
The results show that: in the study population of 54 patients, plasma CRISP3 protein levels correlated positively with organ dysfunction severity scores SOFA (r=0.317, p=0.019), apacii (r=0.068, p=0.624) (fig. 2a and 2 b). Meanwhile, in the study population of 166 patients, plasma CRISP3 protein levels correlated positively with organ dysfunction severity scores SOFA (r=0.481, p < 0.001) (fig. 2 c), apacii (r=0.509, p < 0.001) (fig. 2 d).
Example 3
Early warning efficacy analysis of plasma CRISP3 protein on sepsis occurrence risk
In the study population of 54 and 166 severely wounded patients, PCT, CRP and CRISP3 protein detection values of the corresponding patients are collected simultaneously, ROC curves of early warning of sepsis occurrence risk of each biomarker are drawn, and statistical differences of areas under the ROC curves are compared by using medcalc15.8 software.
The results show that: in the study population of 54 patients, the area under the ROC curve of CRISP3 was 0.811 (0.681-0.905), the sensitivity was 63.64%, the specificity was 90.62%, and the Cut-off value was 1.053ng/ml. The ROC curves for CRP, PCT and SOFA are 0.605 (0.463-0.735), 0.554 (0.412-0.689) and 0.754 (0.618-0.861), respectively. The area under the curve of CRISP3 is significantly larger than CRP (p=0.042), PCT (p=0.004) (fig. 3 a); in the study population of 166 patients, the area under the ROC curve of CRISP3 was 0.772 (0.701-0.834), the sensitivity was 59.26%, the specificity was 82.88%, and the Cut-off value was 1.070ng/ml. The ROC curves for CRP, PCT and SOFA are 0.521 (0.442-0.599), 0.531 (0.452-0.609) and 0.791 (0.717-0.853), respectively. The area under the curve of CRISP3 is significantly larger than CRP (p=0.0004), PCT (p=0.0002) (fig. 3 b). The CRISP3 has a certain value for early warning of sepsis, and the early warning capability is superior to PCT and CRP.
Claims (6)
- Use of a crisp3 protein in the preparation of a marker for early warning of sepsis.
- 2. Use according to claim 1, characterized in that: the marker is CRISP3 protein in serum, plasma or blood.
- 3. Use according to claim 2, characterized in that: the CRISP3 protein expression level in the plasma or serum of patients with sepsis is significantly increased.
- Use of a crisp3 protein in the manufacture of a diagnostic reagent for assessing the efficacy of a sepsis treatment.
- 5. Use according to claim 4, characterized in that: the diagnostic agent plasma is blood, serum or CRISP3 protein in plasma.
- 6. Use according to claim 5, characterized in that: the CRISP3 protein expression level is positively correlated with organ dysfunction severity.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311273691.8A CN117288961A (en) | 2023-09-28 | 2023-09-28 | Application of CRISP3 protein in preparation of biomarker for early warning of sepsis |
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| CN202311273691.8A CN117288961A (en) | 2023-09-28 | 2023-09-28 | Application of CRISP3 protein in preparation of biomarker for early warning of sepsis |
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- 2023-09-28 CN CN202311273691.8A patent/CN117288961A/en active Pending
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