Application of progranulin in the diagnosis, prognosis and treatment of invasive Candida infection

Abstract

The present invention belongs to the field of biomarker technology, and specifically discloses the application of progranulin in the diagnosis, prognosis and treatment of invasive Candida infection. The present invention finds that progranulin can be used as a new biological marker for predicting and diagnosing invasive Candida infection, which can not only be used for the diagnosis of the disease and reflect the severity of the disease, but also can be used as a potential therapeutic target for invasive Candida infection, providing a new technical means for the diagnosis, prognosis and treatment of invasive Candida infection and related diseases.

Description

Technical Field

[0001] The present invention relates to the technical field of biomarkers, and in particular to the application of progranulin in the diagnosis, prognosis and treatment of invasive Candida infection. Background Art

[0002] Candida spp. is one of the most common fungal pathogens of human mucocutaneous and invasive fungal infections. It is the fourth most common cause of related infections in health care institutions. It is estimated that 400,000 life-threatening candidal infections occur each year with a mortality rate of 46-75%. Among the several Candida species that cause infections, 95% of candidal infections are caused by Candida albicans (54%), Candida glabrata (19%), Candida spp. (11%) and Candida tropicalis (11%). With the use of drugs such as broad-spectrum antibiotics, corticosteroids and immunosuppressants, as well as tumor radiotherapy and chemotherapy, the occurrence of immunodeficiency diseases and the indwelling of various medical catheters, the incidence of fungal infections has increased year by year in the clinic and has attracted widespread attention. Based on the high incidence of infection, patient mortality and a large amount of medical burden, it is very important to diagnose candidemia early and find potential therapeutic targets.

[0003] Currently, the main gold standard for the diagnosis of invasive candidiasis is 3D blood culture, but blood culture has poor sensitivity, a long culture positive time, and cannot diagnose deep candidal infections in tissues and organs. In addition to conventional culture methods, the use of serological (1,3)-β-D-glucan (BDG) detection is used as an early diagnostic indicator for invasive candidal infection; another emerging detection method is nucleic acid hybridization probe technology. When the target fungus appears in the culture, the corresponding DNA probe hybridizes with its RNA and can be used for the examination of filamentous fungi or yeast fungi. However, these two methods can only indicate whether the patient has a fungal infection, and cannot predict the infection status and severity of the patient's disease. Summary of the invention

[0004] In view of the shortcomings of the prior art described above, the purpose of the present invention is to provide an application of progranulin in the diagnosis, prognosis and treatment of invasive Candida infection. Progranulin, as a biomarker, can not only be used for the diagnosis of diseases related to invasive Candida infection and reflect the severity of the disease, but it can also serve as a potential therapeutic target for invasive candidiasis, thereby solving the problem that the diagnostic methods for invasive Candida infection in the prior art are not suitable for clinical application.

[0005] To achieve the above objectives and other related objectives, the present invention provides, in a first aspect, the use of progranulin as a biomarker in the preparation or screening of reagents for the diagnosis, prognosis or treatment of invasive Candida infection.

[0006] Furthermore, the reagent is used to measure the expression level of progranulin in a body fluid sample.

[0007] Furthermore, the expression level of progranulin in the body fluid sample is positively correlated with the severity of the disease caused by invasive Candida infection.

[0008] Furthermore, the expression level of progranulin in the body fluid sample was positively correlated with the expression levels of urea nitrogen (Urea) and creatinine (Crea), indicators of kidney damage caused by invasive Candida infection.

[0009] Furthermore, the body fluid sample is selected from serum.

[0010] Furthermore, the invasive Candida infection is a bloodstream infection or disease caused by Candida species.

[0011] Furthermore, the genus Candida includes Candida albicans (C.albicans), Candida parapsilosis (C.parapsilosis), Candida glabrata (C.glabrata), and Candida tropicalis (C.tropicalis), but is not limited thereto.

[0012] Furthermore, the disease includes invasive candidemia (or candidemia) and kidney damage caused by invasive Candida infection, but is not limited thereto.

[0013] The second aspect of the present invention provides a kit for detecting progranulin, wherein the kit is used to diagnose invasive Candida infection by detecting progranulin, and to assess the severity of the disease caused by the invasive Candida infection and the prognosis of the disease.

[0014] The third aspect of the present invention provides the use of a progranulin neutralizing antibody in the preparation of a medicament for improving and / or treating invasive Candida infection.

[0015] The fourth aspect of the present invention provides a drug, which comprises a progranulin neutralizing antibody and is used for improving and / or treating invasive Candida infection.

[0016] Furthermore, the progranulin neutralizing antibody is used to reduce or deplete the level of progranulin.

[0017] Furthermore, the drug must include progranulin neutralizing antibodies, and use the progranulin neutralizing antibodies as the active ingredient for the aforementioned functions.

[0018] Furthermore, in the drug, the active ingredient that exerts the aforementioned function may be only the progranulin neutralizing antibody, or may contain other molecules that can exert similar functions.

[0019] Furthermore, the progranulin neutralizing antibody is used as one of the active ingredients or the only active ingredient of the drug.

[0020] Furthermore, the drug may be a single-component substance or a multi-component substance.

[0021] Furthermore, the drug also includes a pharmaceutically acceptable carrier and / or excipient.

[0022] Furthermore, the form of the drug is not particularly limited and can be in various forms such as solid, liquid, gel, semi-fluid, aerosol, etc.

[0023] Furthermore, the drug is mainly targeted at mammals, and the mammals are preferably rodents, even-toed ungulates, perissodactyls, lagomorphs, primates, etc., and the primates are preferably monkeys, apes or humans.

[0024] Furthermore, the drug can be administered in a variety of forms, such as enteral administration or parenteral administration. It is generally recommended to administer the drug in a known route, such as intraperitoneal injection, for each chemical drug.

[0025] As described above, the use of the granulin precursor of the present invention in the diagnosis, prognosis and treatment of invasive Candida infection has the following beneficial effects:

[0026] The present invention focuses on the application value of progranulin in invasive fungal infection, and finds that progranulin can be used as a new biological marker for predicting and diagnosing invasive candida infection. Serum determination of clinical patients with invasive candidemia and in vivo animal experiments of Candida albicans infection both indicate that PGRN expression levels are elevated, and high expression of PGRN is positively correlated with the severity of the disease, which promotes fatal invasive candidemia. Based on this, the present invention proposes progranulin as a diagnostic and prognostic indicator for invasive candida infection, which can be used for the diagnosis of invasive candidiasis and reflect the severity of the disease. At the same time, it can also serve as a potential therapeutic target for invasive candidiasis, providing new technical means for the diagnosis, prognosis and treatment of invasive candida infection and related diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 The graph shows the expression level of PGRN in the serum of candidemia patients and control patients, as well as patients infected with different bacterial species in Example 1 of the present invention.

[0028] Figure 2 It shows the comparison of renal injury indexes between candidemia patients and control group patients in Example 2 of the present invention, and the result of correlation analysis between PGRN content and renal injury indexes.

[0029] Figure 3 Shown is a comparison chart of serum PGRN levels and survival curves of patients with candidemia who died and those who did not die in Example 3 of the present invention.

[0030] Figure 4 Shown is a statistical diagram of the positive and death diagnosis of the patient serum markers PGRN, Urea, and Crea in invasive Candida infection analyzed by the ROC curve in Example 4 of the present invention.

[0031] Figure 5 Shown is the correlation analysis between PGRN content and kidney injury indicators in the in vivo animal experiment in Example 5 of the present invention, as well as the survival curves of wild mice and PGRN gene-deficient mice.

[0032] Figure 6 Shown is a comparison of the survival curves of the PGRN antibody depletion group and the control group in the in vivo animal experiment in Example 6 of the present invention. DETAILED DESCRIPTION

[0033] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention.

[0034] Progranulin (PGRN), a pleiotropic growth factor, plays an important role in maintaining and regulating the homeostatic dynamics of normal tissue development, proliferation, regeneration, and host defense responses, and has therefore been extensively studied in the fields of infectious diseases, wound healing, tumorigenesis, and neuroproliferative and degenerative diseases. PGRN is also a multifaceted immunomodulatory molecule by regulating signaling pathways that are critical to immunology, especially the TNF / TNFR signaling pathway. PGRN is highly expressed in epithelial cells, certain types of neurons, and macrophages, and is also widely expressed in other tissues and cell types, including skeletal muscle, chondrocytes, adipose tissue, hematopoietic cells, and immune cells, including T cells and dendritic cells. PGRN has multiple physiological functions and is involved in a variety of disease processes, including autoimmune diseases, cancer, and neurodegenerative diseases. It has become a multifaceted immunomodulatory molecule by regulating signaling pathways known to be critical to immunology, especially the TNF / TNFR signaling pathway. It is easy to conclude that PGRN has the potential to be immunomodulatory, anti-inflammatory, and treat a variety of inflammatory diseases. It has pro-inflammatory or anti-inflammatory activities, depending on the stages and components involved in the tissue microenvironment, but its role in invasive Candida infections has not been reported so far.

[0035] Through a series of studies, the present invention found that PGRN, as a new cytokine, is involved in the diagnosis and prognosis of invasive Candida infection. Based on this, the present invention provides a new diagnostic method for invasive Candida infection in clinical practice.

[0036] The embodiment of the present invention uses the ELISA method to detect the serum of 68 patients with candidemia and 52 patients with negative pathogen detection, and it is found that the PGRN level in patients with candidemia is significantly higher than that in healthy controls, and there is a significant statistical difference. Further analysis of the PGRN change levels of dead patients and surviving patients found that PGRN was highly expressed in dead patients and had a statistical difference compared with surviving patients. Survival curve analysis found that PGRN promoted the death of invasive candidemia patients when it was highly expressed. Subsequently, the ROC curve was used to analyze the diagnostic value of PGRN, Urea, and Cre in invasive fungal infections, and it was found that the area under the curve covered by the marker PGRN was the largest, followed by Urea, and the area under the curve of PGRN was higher than that of Urea and Cre, indicating that PGRN can be used as a diagnostic indicator for invasive Candida infection.

[0037] Further, the present invention embodiment found through the study of the invasive Candida infection mouse model that the use of Candida albicans infection can cause the PGRN expression level of mice to increase, and is positively correlated with the kidney injury indicators urea nitrogen (Urea) and creatinine (Crea), and has statistical differences. Therefore, it can be fully considered that PGRN plays a role in invasive Candida infection. Subsequently, the present invention embodiment used Candida infection wild-type mice and PGRN gene-deficient mice to conduct experiments. The experimental results showed that the survival rate and weight curve of PGRN gene-deficient mice compared with wild-type mice were significantly improved, and there were statistical differences. Finally, the present invention embodiment was reversely verified, using PGRN neutralizing antibodies in mice to deplete PGRN, and a model was established to observe the changes in survival rate. It was found that the survival rate after depletion and neutralization of PGRN was improved compared with the wild control, and there were statistical differences. The above results show that the excessive expression of PGRN accelerates the pathological damage of the kidneys, resulting in a significant decrease in the quality of life of the host. Therefore, the high expression of PGRN can be used as an indicator to assess the severity of the disease and can be used as a potential therapeutic target.

[0038] The following specific examples are given to illustrate the present invention in detail. It should also be understood that the following examples are only used to specifically illustrate the present invention and cannot be understood as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made by those skilled in the art based on the above content of the present invention belong to the scope of protection of the present invention. The specific experimental parameters of the following examples are also only an example within a suitable range, that is, those skilled in the art can make a selection within a suitable range through the description of this article, and are not limited to the specific values ​​​​exemplified below.

[0039] Example 1

[0040] Detection of changes in serum PGRN levels and renal function indicators in patients with Candida bloodstream infection.

[0041] The inclusion criteria for patients with invasive candidemia were positive blood culture for Candida albicans. The blood samples were tested for relevant pathogens by the Microbiology Laboratory of the Laboratory Department of the First Affiliated Hospital of Chongqing Medical University. After the test confirmed that it was Candida bloodstream infection, the serum samples of the patients were collected on the day of the test. At the same time, the serum samples of patients with negative pathogen tests were collected in the laboratory as healthy controls. The exclusion criteria for patients with negative pathogen tests were patients with underlying diseases such as cancer, diabetes, autoimmune diseases, and other acute and chronic infections that affected the expression of PGRN. The samples were immediately frozen in a -80°C refrigerator for subsequent experiments. The patient's basic personal information, hospitalization days, renal function indicators, and infected bacteria were recorded in full.

[0042] All patients were divided into two groups: patients with candidasis and healthy control. The serum of 68 patients with candidasis and 52 patients with negative pathogen detection was tested by ELISA. The concentration of PGRN in the serum of patients was detected by human PGRN ELISA kit (purchased from R&D Systems, Cat#DPGRN0). The specific operation steps were strictly referred to the instructions of the kit. SPSS 20.0 was used for statistical analysis and GraphPad Prism 8.0 software was used for drawing.

[0043] Figure 1 Shown is the expression level of PGRN in the serum of candidemia patients and control patients and patients infected with different bacterial species in this example.

[0044] like Figure 1 As shown in A, the PGRN content (ng / ml) in the serum of patients with invasive Candida infection was significantly increased, which was statistically significant compared with the healthy control group (ng / ml); Figure 1 As shown in B, the PGRN content in the serum of patients infected with the most virulent Candida albicans was the highest, and the PGRN content in the serum of patients infected with the weakest Candida glabrata was significantly higher and statistically significant. The above experimental results show that PGRN plays a certain role in Candida bloodstream infection and is related to the virulence of the strain.

[0045] Example 2

[0046] Serum PGRN concentration was positively correlated with renal damage in patients with candidemia.

[0047] In the case analysis of human invasive Candida infection and the mouse invasive fungal infection model, the kidney is the main target organ of Candida infection. Therefore, this example evaluates the severity of the disease by assessing the damage indicators of the kidneys of patients with invasive candidemia.

[0048] The laboratory parameters of patients with invasive candidemia and those with negative pathogen tests were collected through the LIS system of the laboratory department. The renal function indicators Urea and Crea in patients with candidemia and those in the control group were compared. The renal function indicators Urea, Crea and the corresponding serum PGRN expression of each patient were correlated and analyzed using GraphPad Prism 8.0.1 software.

[0049] Figure 2 Shown is a comparison of renal injury indicators between candidemia patients and control patients in this example, and a correlation analysis result diagram of PGRN content and renal injury indicators.

[0050] like Figure 2 As shown in A and 2B, the renal function indicators Urea and Crea in patients with invasive candidemia were significantly higher than those in patients with negative pathogen detection, and the increase was statistically significant. Figure 2 As shown in C and 2D, the correlation analysis of renal function indexes Urea, Crea and PGRN expression showed that the correlation coefficient between PGRN and Urea was r=0.3861, P=0.0062; the correlation coefficient between PGRN and Crea was r=0.3861, P=0.0062, which was statistically significant. The above experimental results suggest that PGRN is positively correlated with renal damage in patients with invasive candidemia.

[0051] Example 3

[0052] Comparison of serum PGRN levels between non-fatal and fatal patients with candidemia, and analysis of PGRN concentration and patient survival curve.

[0053] The statistical analysis of Example 2 revealed that PGRN was positively correlated with the degree of renal damage in patients with invasive candidemia, and therefore continued attention was paid to the final disease outcome of patients with candidemia.

[0054] According to all the patient medical records retrieved from the LIS system of the laboratory department, 68 patients with candidemia were divided into two groups: non-mortem patients and non-mortem patients, including 42 non-mortem patients and 26 non-mortem patients, and the changes in serum PGRN concentrations were compared; PGRN concentrations were used to predict the correlation between non-mortem and non-mortem patients, with 92.72 ng / ml as the cut-off value, and the survival days of the patients were counted, and the Kaplan Meier survival rate curve was drawn. SPSS 20.0 was used for statistical analysis, and GraphPad Prism 8.0.1 software was used for graphics.

[0055] Figure 3 Shown is a comparison chart of serum PGRN levels and survival curves between patients who died of candidemia and those who did not die in this example.

[0056] like Figure 3 As shown in A, the serum PGRN concentration of the survivors in patients with invasive candidemia was significantly higher than that of the non-survivors, and the difference was statistically significant. Figure 3 As shown in Figure B, the survival rate curve based on the survival days of patients with invasive candidemia shows that when the PGRN concentration is higher than 92.72 ng / ml, the patient mortality rate increases, while when the PGRN concentration is lower than 92.72 ng / ml, the patient survival rate is better. The above results suggest that in patients with invasive candidemia, the level of PGRN in the serum reflects the severity of the patient's disease and is related to the patient's final survival outcome.

[0057] Example 4

[0058] ROC curve analysis was used to compare the diagnostic efficacy of serum PGRN, Urea, and Crea for invasive candidemia infection and death.

[0059] The laboratory parameters of patients in the candidemia group and the control group, including PGRN, Urea and Crea, were collected through the laboratory department's LIS system. Using the data of PGRN, Urea and Crea, the ROC curve analysis was used to compare the diagnostic efficacy of the three types of indicators for patients with positive invasive candidemia and patients with death from invasive candidemia. SPSS20.0 software was used to draw the ROC curve, and MedCalc15.8 software was used to compare the statistical differences in the area under the ROC curve.

[0060] Figure 4 Shown is a statistical diagram of the positive and death diagnosis of the patient serum markers PGRN, Urea, and Crea in invasive Candida infection analyzed by ROC curve in this example.

[0061] like Figure 4As shown in A and Table 1 , the ROC curve analysis of the diagnostic value of different indicators in patients with positive invasive candidemia showed that the areas under the curve of serum PGRN, Urea, and Crea were 0.820, 0.813, and 0.643, respectively.

[0062] From the above statistical results, it was found that the area under the curve of PGRN was significantly larger than that of Urea and Crea, and was statistically significant, indicating that PGRN had a certain diagnostic value for invasive Candida positive infection and was optimal.

[0063] Table 1. ROC curve analysis of PGRN / Urea / Cre in predicting the correlation of candidemia-positive patients

[0064]

[0065] like Figure 4 B and as shown in Table 2 , the ROC curve analysis of different indicators in the diagnosis of patients with invasive candidemia and death showed that the areas under the curve of serum PGRN, Urea, and Crea were 0.805, 0.775, and 0.598, respectively.

[0066] From the above statistical results, it was found that the area under the curve of PGRN was significantly larger than that of Urea and Crea, and was statistically significant, indicating that PGRN had a certain diagnostic value for patients with invasive candidemia and was optimal.

[0067] Table 2. Comparison of the correlation between PGRN / Urea / Cre in predicting candidemia deaths

[0068]

[0069] Example 5

[0070] In order to further clarify that Candida albicans infection causes increased expression levels of PGRN, this example used wild-type and PGRN gene knockout mice to construct an animal model of bloodstream infection.

[0071] The experimental mice included 6-8 week old female C57BL / 6 mice (purchased from Beijing Weitonglihua Biotechnology Co., Ltd.) and 6-8 week old female PGRN gene-deficient (PGRN^(- / -)) mice (purchased from Jackson Laboratory, USA). They were randomly divided into groups and each experiment was repeated at least twice.

[0072] To investigate whether the positive correlation between human PGRN concentration and renal injury in patients with invasive candidemia can also be confirmed in animal models, 20 wild mice were injected with 4 × 10 suspension of Candida albicans into the tail vein. 5cfu, a mouse PGRN ELISA kit (purchased from R&D Systems, Cat# DY2557-05) was used to detect changes in PGRN in mouse serum, and the OCD biochemical pipeline of the laboratory department determined the mouse kidney injury indicators Urea and Crea.

[0073] At the same time, to further verify the damaging effect of PGRN in invasive candida albicans, 20 wild mice and 20 PGRN^(- / -) mice of similar age and weight were randomly divided into groups and injected with 4×10 suspension of Candida albicans into the tail vein at the same time. 5 cfu, the survival rate and body weight curve of mice were observed and recorded daily, the results were analyzed for normality using SPSS20.0 software, and graphed using GraphPad Prism 8.0.1 software. Normal data were expressed as mean ± standard deviation.

[0074] The results of the determination of mouse serum PGRN concentration and kidney injury indicators Urea and Crea are shown in Table 3:

[0075] Table 3. Serum PGRN concentration in mice and the results of determination of renal injury indicators Urea and Crea

[0076] PGRN (ng / ml) Urea(umol / L) Crea(umol / L) 164.4937 13.7 47 178.9877 13.1 49 281.0999 38.4 101 158.3264 16.6 39 143.8555 18 32 212.2218 111.2 116 179.5822 96 148 224.6986 57.2 128 158.3264 13.5 31 140.6569 73.8 138 166.9396 53.2 76 98.04969 11.2 42 168.766 12.1 33 115.7313 12.3 29 134.2031 13.9 33 128.3302 13.1 28 54.56532 9.8 27 54.56532 11.2 33 89.71704 10.1 25 81.98341 11.8 32

[0077] Figure 5 Shown is the correlation analysis between PGRN content and kidney injury index in the in vivo animal experiment in this example, as well as the survival curve of wild mice and PGRN gene-deficient mice.

[0078] like Figure 5 As shown in A and 5B, after Candida infection in mice, the content of PGRN in the kidney was proportional to the degree of kidney damage, and there was a statistical difference, indicating that high expression of PGRN would lead to more severe kidney damage in the host; Figure 5 C, 5D, wild-type mice and PGRN - / - Comparison of the survival rates of mice infected with Candida albicans revealed that PGRN - / - The survival rate of mice reached 75%, while that of wild mice was only 12.5%. There was a significant statistical difference between the two, which further demonstrated that PGRN promoted the occurrence and development of candidemia and aggravated the mortality rate of candidemia.

[0079] Example 6

[0080] Depletion of PGRN levels in mice using PGRN antibodies can significantly improve the survival rate of mice with candidemia.

[0081] The relevant data of the above examples have confirmed that PGRN plays a damaging role in candidemia and promotes the occurrence and development of fatal candidemia. In order to further reversely verify its damaging effect and possible therapeutic target for the disease, 10 wild female C57BL / 6J mice aged 6-8 weeks (purchased from Beijing Weitong Lihua Biotechnology Co., Ltd.) were randomly selected from the experimental group of this example, and 5ug of PGRN neutralizing antibody Mouse Progranulin / PGRN Antibody (purchased from R&D Systems, Cat#AF2557) was intraperitoneally injected to deplete PGRN in vivo. The wild-type mice in the control group were intraperitoneally injected with 5ug Goat IgG control protein, and two hours later, 4*10 5 cfu Candida albicans suspension and observe and record the changes in survival rate every day. The Kaplan Meier curve of survival rate was drawn and analyzed and plotted using GraphPad Prism 8.0.1 software.

[0082] Figure 6 Shown is a comparison of the survival curves of the PGRN antibody depletion group and the control group in the in vivo animal experiment in this example.

[0083] like Figure 6 As shown, after wild-type mice were intraperitoneally injected with Mouse PGRN antibody to deplete PGRN in the body, the Candida albicans model was observed for 25 days. It was found that compared with mice injected intraperitoneally with Mouse PGRN antibody, the mortality rate of WT+lg Gcontrol mice reached 100%, and the survival time was significantly shorter than that of WT+anti-PGRN. The injection of Mouse PGRN antibody significantly improved the survival rate of candidemia mice, suggesting that Mouse PGRN antibody has the potential to treat invasive candidemia, and PGRN is a therapeutic target for the occurrence and development of candidemia.

[0084] In summary, the embodiment of the present invention firstly measured the expression of PGRN in patients with invasive candidemia and found that it was significantly increased, and the degree of increase was related to the virulence of the strain infected by the patient. At the same time, it was analyzed that PGRN was positively correlated with the kidney damage severity indicators Urea and Crea of ​​the infected patients; secondly, in the analysis of the disease prognosis and survival of the patients, it was found that PGRN was highly expressed in the dead patients compared with the surviving patients, and its high expression promoted the death of the infected patients; ROC curve analysis found that PGRN can be used as a new biological marker for diagnosing invasive Candida infection and death of infected patients; further in vivo animal experiments were established and found that Candida albicans can cause an increase in the expression level of PGRN, and the high expression of PGRN is positively correlated with the severity of the disease. After the infection model was established using wild and PGRN gene-deficient mice, it was found that the survival rate was significantly improved after PGRN gene deficiency; finally, after using PGRN antibody to deplete PGRN in mice, it was found that it could significantly improve the survival rate of invasive candidemia, suggesting that PGRN antibodies may have the potential to treat invasive candidemia. Based on this, the present invention provides PGRN as a diagnostic and prognostic indicator for invasive Candida infection, as well as a potential therapeutic target.

[0085] The above embodiments are merely illustrative of the principles and effects of the present invention, and are not intended to limit the present invention. Anyone familiar with the art may modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by a person of ordinary skill in the art without departing from the spirit and technical concept disclosed by the present invention shall still be covered by the claims of the present invention.

Claims

1. Use of progranulin as a biomarker in the preparation or screening of diagnostic or prognostic reagents for invasive Candida infection, characterized in that: The reagent is used to measure the expression level of progranulin in a body fluid sample, and the expression level of progranulin in the body fluid sample is positively correlated with the severity of the disease caused by invasive Candida infection; The invasive Candida infection is a bloodstream infection caused by Candida species, and the bloodstream infection caused by Candida species is invasive candidemia and renal damage in patients with invasive candidemia.

2. The use according to claim 1, characterized in that: The genus Candida includes Candida albicans, Candida parapsilosis, Candida glabrata and Candida tropicalis.

3. Use of a progranulin neutralizing antibody in the preparation of a medicament for improving and / or treating invasive Candida infection, characterized in that: The progranulin neutralizing antibody is used to reduce or deplete the level of progranulin; the invasive Candida infection is a bloodstream infection caused by Candida spp., and the bloodstream infection caused by Candida spp. is invasive candidemia and renal damage in patients with invasive candidemia.

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