Application of soluble factor in asymptomatic neurosyphilis detection

Abstract

The invention relates to an application of a soluble factor in asymptomatic neurosyphilis detection. Specifically, the invention provides an application of soluble factors such as IL-12p70, IL-10, IL-8 and the like in preparation of a product for detecting the asymptomatic neurosyphilis. The invention also provides an evaluation system for evaluating the risk of the patient suffering from the asymptomatic neurosyphilis. The evaluation system comprises a detection module and a judgment module and performs evaluation based on the cerebrospinal fluid concentration of the soluble factor. According to the method, the asymptomatic neurosyphilis can be distinguished from other types of syphilis, especially latent syphilis, so that early recognition and early treatment of the asymptomatic neurosyphilis are realized, and the asymptomatic neurosyphilis is prevented from being developed into symptomatic neurosyphilis.

Description

[0001] This application requests the priority of the invention patent whose applicant is "Beijing Ditan Hospital Affiliated to Capital Medical University", whose invention name is "Application of soluble factors in the detection of asymptomatic neurosyphilis" and whose application number is "202311737370.9". Technical Field

[0002] The invention relates to the technical field of biomedicine, and in particular to the application of soluble factors in the detection of asymptomatic neurosyphilis. Background Art

[0003] Syphilis is a serious sexually transmitted disease caused by Treponema pallidum (T. pallidum) and is the most common sexually transmitted disease.

[0004] Neurosyphilis is a group of clinical syndromes caused by the invasion of the nervous system by Treponema pallidum. Neurosyphilis can occur at any time after the initial syphilis infection.

[0005] Neurosyphilis first invades the cerebrospinal fluid, which may occur soon after infection with Treponema pallidum. Neurosyphilis has a variety of clinical manifestations, some of which show clinical symptoms, while others do not. Therefore, it is usually clinically divided into asymptomatic neurosyphilis (ANS) and symptomatic neurosyphilis (SNS) (such as meningeal neurosyphilis, meningovascular neurosyphilis, tabes dorsalis and paralytic dementia).

[0006] Although asymptomatic neurosyphilis has no obvious symptoms and signs, there are abnormal changes in cerebrospinal fluid, and the probability of developing symptomatic neurosyphilis is as high as 87% if the abnormal cerebrospinal fluid persists for more than 5 years. Therefore, early identification, early diagnosis, and early treatment of neurosyphilis, especially asymptomatic neurosyphilis, are very important. Finding biomarkers that can identify asymptomatic neurosyphilis is of great significance for preventing asymptomatic neurosyphilis from developing into symptomatic neurosyphilis at an early stage.

[0007] Currently, the diagnosis of asymptomatic neurosyphilis mainly relies on cerebrospinal fluid (CSF) examination, including CSF white blood cell count (CSF wbc) and cerebrospinal fluid protein level (CSF protein).

[0008] It is reported that the increased protein content in the cerebrospinal fluid of patients with neurosyphilis is positively correlated with the severity of the disease and negatively correlated with the long-term prognosis. Increased leukocytosis and increased protein levels in the cerebrospinal fluid indicate the presence of intracranial inflammatory reactions, which are helpful for the diagnosis of neurosyphilis. However, in some patients with asymptomatic neurosyphilis, the cerebrospinal fluid leukocyte count or protein level is within the normal range, and it is especially common for the cerebrospinal fluid protein to be normal, which cannot truly reflect the condition, resulting in the frequent missed diagnosis or misdiagnosis of asymptomatic neurosyphilis.

[0009] Latent syphilis (or latent syphilis, LS) is divided into early latent syphilis and late latent syphilis. Early latent syphilis is defined as the following: a) having a clear history of unsafe sexual intercourse within the past two years, but no history of unsafe sexual intercourse two years ago; b) having clinical manifestations consistent with primary or secondary syphilis, but not being diagnosed and treated at the time; c) having a sexual partner with a clear history of early syphilis infection. Late latent syphilis is usually defined as the following: infection time is more than two years; it is particularly important to note that those who cannot determine the time of infection are also considered to have late latent syphilis; and there is no clear history of syphilis diagnosis or treatment.

[0010] Whether it is early latent syphilis or late latent syphilis, there are no clinical manifestations of syphilis, no symptoms and signs of nervous system damage, only positive syphilis serological tests and non-treponemal serological tests, and asymptomatic neurosyphilis also has no obvious symptoms and signs, and the two are not easy to distinguish. If the titer of non-treponemal serological tests does not decrease after regular anti-syphilis treatment for patients with latent syphilis, especially the syphilis serum fixation phenomenon that has been troubling patients and medical staff, it needs to be differentiated from asymptomatic neurosyphilis. Only with appropriate treatment under correct diagnosis can clinical cure or prevent the disease from worsening and developing into symptomatic neurosyphilis.

[0011] Since latent syphilis and asymptomatic neurosyphilis have no obvious clinical symptoms and signs, they are often easily confused in clinical practice. However, the treatment and prognosis of the two are completely different. Only early and correct diagnosis and subsequent correct treatment can achieve clinical cure, reduce the incidence of symptomatic neurosyphilis, and reduce the disability rate of neurosyphilis. Therefore, it is of great significance to distinguish between the two. Summary of the invention

[0012] A first aspect of the present invention provides a kit for detecting asymptomatic neurosyphilis, the kit comprising a factor detection reagent for detecting the concentration of a soluble factor in cerebrospinal fluid, wherein the soluble factor is selected from any one or a combination of any two or more of IL-12p70, IL-10, TNF-α, IP-10, IL-8, RANTES and GRO-α.

[0013] The second aspect of the present invention provides the use of soluble factors in preparing a product for detecting asymptomatic neurosyphilis.

[0014] The third aspect of the present invention provides an evaluation system for evaluating the risk of a patient suffering from asymptomatic neurosyphilis, the evaluation system comprising a detection module and a judgment module; wherein:

[0015] The detection module is used to detect the cerebrospinal fluid concentration of soluble factors; the evaluation module includes a readable carrier storing evaluation rules;

[0016] The evaluation rule is: when the cerebrospinal fluid concentration of the detected soluble factor is higher than the corresponding cutoff value (also called cutoff value), the syphilis patient is evaluated as having a high risk of suffering from asymptomatic neurosyphilis; otherwise, the syphilis patient is evaluated as having a low risk of suffering from asymptomatic neurosyphilis;

[0017] The soluble factor is any one or a combination of any two or more selected from IL-12p70, IL-10, TNF-α, IP-10, IL-8, RANTES and GRO-α.

[0018] Compared with the prior art, the present invention can distinguish asymptomatic neurosyphilis from other types of syphilis, especially latent syphilis, thereby achieving early identification and early treatment of asymptomatic neurosyphilis and preventing it from developing into symptomatic neurosyphilis with serious consequences. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 Comparison of the expression levels of soluble factors IL-12p70, IL-10, TNF-α, IP-10, IL-8, RANTES, and GRO-α in latent syphilis (LS, n=29) and asymptomatic neurosyphilis (ANS, n=30) are shown. Each box plot includes the lower quartile (lower horizontal line), median (middle horizontal line), and upper quartile (upper horizontal line). Student's T-Test was used to compare the normally distributed data between the two groups, and the Mann-Whitney U test was used to compare the non-normally distributed data. p values ​​≤ 0.05 were considered statistically significant.

[0020] Figure 2 Comparison of the expression levels of soluble factors IFN-γ, IL-6, Eotaxin, IL-2, MCP-1, TNF-β, and IFN-α in the LS (n=29) and ANS (n=30) groups is shown. Each box plot includes the lower quartile (lower horizontal line), median (middle horizontal line), and upper quartile (upper horizontal line). Student's T-Test was used to compare the normally distributed data between the two groups, and Mann-Whitney U test was used to compare the non-normally distributed data. p value ≤ 0.05 was considered statistically significant.

[0021] Figure 3Comparison of the expression levels of clinical parameters cerebrospinal fluid white blood cell count (CSF wbc) and cerebrospinal fluid protein level (CSF protein) in the LS (n=29) and ANS (n=30) groups is shown. Each box plot includes the lower quartile (lower horizontal line), median (middle horizontal line) and upper quartile (upper horizontal line). Student's T-Test was used to compare the normally distributed data between the two groups, and Mann-Whitney U test was used to compare the non-normally distributed data. p value ≤ 0.05 was considered statistically significant. DETAILED DESCRIPTION

[0022] In order to make the purpose, technical scheme and advantages of the present invention clearer, the technical scheme of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. However, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments described in this application, all other embodiments obtained by ordinary technicians in this field without making creative work belong to the scope of protection of the present invention.

[0023] As described above, the present invention provides in a first aspect a kit for detecting asymptomatic neurosyphilis, the kit comprising a factor detection reagent for detecting the concentration of a soluble factor in cerebrospinal fluid, wherein the soluble factor is selected from any one of IL-12p70, IL-10, TNF-α, IP-10, IL-8, RANTES and GRO-α, or a combination of any two or more thereof.

[0024] The inventors have found that the cerebrospinal fluid concentration of any one or any combination of two or more selected from IL-12p70, IL-10, TNF-α, IP-10, IL-8, RANTES and GRO-α can be used to detect whether a syphilis patient without symptoms of nervous system damage suffers from asymptomatic neurosyphilis. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) drawn according to the cerebrospinal fluid concentration of the soluble factor is greater than 0.7 and the corresponding p value is less than or equal to 0.05.

[0025] In the present invention, the combination of any two or more factors may be, for example, a combination of any two factors or even a combination of all factors. For example, in the aforementioned embodiment, the combination of any two or more factors may be a combination of any two factors, a combination of any three factors, a combination of any four factors, a combination of any five factors, a combination of any six factors or a combination of all seven factors.

[0026] In some preferred embodiments, the soluble factor is any one selected from IL-12p70, IL-10, TNF-α, IP-10, IL-8 and RANTES, or a combination of any two or more thereof, for example, a combination of any two, three, four, five or all six thereof.

[0027] In some preferred embodiments, the soluble factor is any one selected from IL-12p70, IL-10 and TNF-α or a combination of any two or more thereof, for example, a combination of any two or all three thereof.

[0028] In some more preferred embodiments, the soluble factor is IL-12p70 and / or IL-10.

[0029] In some further preferred embodiments, the soluble factor is IL-12p70. Interleukin-12p70 (IL-12p70) is a heterodimeric protein in structure, including a 35kDa subunit (p35) and a 40kDa subunit (p40), which is mainly produced by antigen presenting cells such as monocytes, macrophages and dendritic cells. The two subunits, p35 and p40, are linked together by a disulfide bridge, are genetically unrelated, and have not been reported to have biological activity.

[0030] Although IL-12p70 itself and its expression in various diseases have been reported, its expression in different diseases is different, and there has never been a report that IL-12p70 is related to syphilis, let alone that IL-12p70 can be related to neurosyphilis, especially asymptomatic neurosyphilis. The inventors have found through research that the IL-12p70 cerebrospinal fluid concentration can have an ROC AUC of up to 0.879 when distinguishing latent syphilis from asymptomatic neurosyphilis, and the p value is 0.000. Among the many soluble factors used in the study, it is the most suitable soluble factor for detecting asymptomatic neurosyphilis.

[0031] In some preferred embodiments, the kit further comprises a leukocyte detection reagent for detecting leukocyte count in cerebrospinal fluid. The inventors have found that leukocyte count in cerebrospinal fluid can also be used to distinguish asymptomatic neurosyphilis from other syphilis such as latent syphilis.

[0032] In some preferred embodiments, the factor detection reagent is an antibody or antibody pair against the corresponding soluble factor; preferably, the antibody is a monoclonal antibody against the corresponding soluble factor; and preferably, the antibody pair is a combination of a coating antibody and a detection antibody for detecting the corresponding soluble factor.

[0033] The second aspect of the present invention provides the use of a soluble factor in the preparation of a product for detecting asymptomatic neurosyphilis, wherein the soluble factor is selected from any one or a combination of any two or more of IL-12p70, IL-10, TNF-α, IP-10, IL-8, RANTES and GRO-α.

[0034] In some preferred embodiments, the product is any one of a kit, a detection chip and a detection array.

[0035] In some preferred embodiments, the kit is the kit described in the first aspect of the present invention.

[0036] In some preferred embodiments, the detection chip is a detection chip loaded with at least the factor detection reagent (i.e., a detection reagent for detecting the concentration of soluble factors in cerebrospinal fluid). In other preferred embodiments, the detection array is a detection array loaded with at least the factor detection reagent (i.e., a detection reagent for detecting the concentration of soluble factors in cerebrospinal fluid).

[0037] In some preferred embodiments, the detection chip and the detection array are independently further loaded with a leukocyte detection reagent for detecting the leukocyte count in cerebrospinal fluid.

[0038] The third aspect of the present invention provides an evaluation system for evaluating the risk of a patient suffering from asymptomatic neurosyphilis, the evaluation system comprising a detection module and a judgment module; wherein:

[0039] The detection module is used to detect the cerebrospinal fluid concentration of soluble factors; the judgment module includes a readable carrier storing evaluation rules;

[0040] The evaluation rule is: when the cerebrospinal fluid concentration of the soluble factor is detected to be higher than the cutoff value, the syphilis patient is evaluated as having a high risk of suffering from asymptomatic neurosyphilis; otherwise, the syphilis patient is evaluated as having a low risk of suffering from asymptomatic neurosyphilis;

[0041] The soluble factor is selected from any one or a combination of any two or more of IL-12p70, IL-10, TNF-α, IP-10, IL-8, RANTES and GRO-α, preferably selected from any one or a combination of any two or more of IL-12p70, IL-10, TNF-α, IP-10, IL-8 and RANTES, more preferably selected from any one or a combination of any two or more of IL-12p70, IL-10 and TNF-α, further preferably IL-12p70 and / or IL-10, and further preferably IL-12p70.

[0042] In some embodiments, the detection module may further have the ability to detect the leukocyte count of cerebrospinal fluid. For example, in order to enable the detection module to have the ability to detect the leukocyte count of cerebrospinal fluid, a detection reagent for detecting the leukocyte count of cerebrospinal fluid may be loaded on the detection module, such as the leukocyte detection reagent described above. More specifically, the present invention provides an assessment system for assessing a patient's risk of suffering from asymptomatic neurosyphilis, the assessment system comprising a detection module and a judgment module; wherein: the detection module is used to detect the cerebrospinal fluid concentration of soluble factors and the cerebrospinal fluid leukocyte count; the judgment module comprises a readable carrier storing an assessment rule; the assessment rule is: when the cerebrospinal fluid concentration of the soluble factor is detected to be higher than the corresponding cutoff value, the syphilis patient is assessed as having a high risk of suffering from asymptomatic neurosyphilis; when the cerebrospinal fluid concentration of the soluble factor is detected to be lower than the corresponding cutoff value, it is further determined based on the cerebrospinal fluid leukocyte count, when the cerebrospinal fluid leukocyte count is detected to be greater than 5 / uL, the syphilis patient is assessed as having a high risk of suffering from asymptomatic neurosyphilis, otherwise, the syphilis patient is assessed as having a low risk of suffering from asymptomatic neurosyphilis.

[0043] Example

[0044] The present invention will be illustrated below by examples, but the protection scope of the present invention is not limited to these examples.

[0045] 1. Subjects’ conditions

[0046] In the embodiments of the present invention, the inventors recruited 59 patients from Beijing Ditan Hospital affiliated to Capital Medical University according to the 2018 health industry standards of the People's Republic of China, including 29 patients with latent syphilis (LS) and 30 patients with asymptomatic neurosyphilis (ANS). None of these patients were diagnosed with AIDS. Among them, the specific criteria for latent syphilis patients and asymptomatic neurosyphilis patients are as follows:

[0047] 1.1 Criteria for latent syphilis (LS)

[0048] (1) History of syphilis infection;

[0049] (2) positive serum non-treponemal test;

[0050] (3) positive serum Treponema pallidum test;

[0051] (4) No clinical manifestations of syphilis;

[0052] (5) No symptoms or signs of neurological damage;

[0053] (6) No abnormalities were found in CSF.

[0054] 1.2 Criteria for diagnosis of asymptomatic neurosyphilis (ANS)

[0055] (1) History of syphilis infection;

[0056] (2) positive serum Treponema pallidum test;

[0057] (3) No symptoms or signs of neurological damage;

[0058] (4) CSF VDRL (TRUST) test is positive; or CSF VDRL (TRUST) test is negative, and CSF Treponema pallidum test is positive or CSF white blood cells > 5 / μl or CSF protein > 45 mg / dl.

[0059] The examples of the present invention were approved by the Ethics Committee of Beijing Ditan Hospital Affiliated to Capital Medical University, and all participants provided signed informed consent.

[0060] 2. Sample Collection

[0061] Patient CSF samples were collected as part of routine diagnostic workup. After lumbar puncture, 2 mL CSF samples were obtained. The supernatant of CSF was extracted by centrifugation at 1500 rpm for 10 minutes and stored at -80°C until analysis.

[0062] 3. CSF soluble factor concentration determination

[0063] In order to compare the concentrations of soluble factors, the present inventors used the Luminex xMAP method (ProcartaPlex Human Cytokine / Chemokine / Growth Factor Panel 1 (45plex) 96 tests, AffymetrixeBioscience Ltd., Hatfield, United Kingdom) to detect 45 soluble factors in the CSF of the two groups of patients according to the manufacturer's instructions. These soluble factors (sometimes referred to as soluble proteins) include:

[0064] (1) 29 cytokines: IL-1RA, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8 (or CXCL8), IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, IL-31, TNF-α, TNF-β, IFN-α, IFN-γ, brain-derived neurotrophic factor (BDNF), granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), and leukemia inhibitory factor (LIF);

[0065] (2) 8 chemokines: growth-regulated oncogene α (GRO-α, also known as CXCL1), MCP-1 (also known as CCL2), macrophage inflammatory protein 1α (MIP-1α, also known as CCL3), MIP-1β (also known as CCL4), regulatory factor expressed and secreted on activated normal T cells (RANTES, also known as CCL5), IFN-γ-induced protein 10 (IP-10, also known as CXCL10), eotaxin (also known as CCL11), and stromal cell-derived factor 1α (SDF-1α, also known as CXCL12);

[0066] (3) 8 growth factors: epidermal growth factor (EGF), fibroblast growth factor (FGF-2), hepatocyte growth factor (HGF), β-nerve growth factor (β-NGF), platelet-derived growth factor BB (PDGF-BB), placental growth factor (PLGF), vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor (VEGF-D).

[0067] 4. Statistical analysis

[0068] Statistical analysis was performed using the R program (https: / / cran.r-project.org / ), SPSS (IBM Corporation, New York, NY, USA), or GraphPad Prism 7 (GraphPad Software, La Jolla, CA, USA). Data were presented as mean ± standard deviation for normally distributed data, and as median (interquartile range) for non-normally distributed data. Student's T-Test was used to compare normally distributed data between the two groups, and Mann-Whitney U test was used to compare non-normally distributed data. A p value ≤ 0.05 was considered statistically significant.

[0069] 5. Data Processing

[0070] (1) Detection of intergroup differences

[0071] GraphPad Prism 7 software was used to perform statistical analysis of the differences in different parameters between the two groups. For normally distributed data, the data were presented as mean ± standard deviation, while for non-normally distributed data, the data were presented as median (interquartile range). Student's T-Test was used to compare the normally distributed data between the two groups, and Mann-Whitney Utest test was used to compare the non-normally distributed data. A p value ≤ 0.05 was considered statistically significant.

[0072] (2) ROC analysis

[0073] SPSS software was used to perform ROC analysis to evaluate the diagnostic accuracy of each parameter. AUC was used to evaluate the discriminatory ability of each parameter.

[0074] 6. Results Analysis

[0075] Figure 1 and 2 The expression levels of some soluble factors in the LS and ANS groups are compared. Each box plot includes the lower quartile (lower horizontal line), median (middle horizontal line) and upper quartile (upper horizontal line). Student's T-Test was used to compare the normally distributed data between the two groups, and Mann-Whitney U test was used to compare the non-normally distributed data. p value ≤ 0.05 was considered statistically significant. Figure 1 and 2 It can be seen that the expression levels of soluble factors IL-12p70, IL-10, TNF-α, IP-10, IL-8, RANTES, GRO-α, IL-6, and IFN-α in the ANS group were significantly higher than those in the LS group, while there was no significant difference in the expression levels of soluble factors IFN-γ, Eotaxin, IL-2, MCP-1, and TNF-β between the LS and ANS groups.

[0076] Figure 3 Comparison of the expression levels of clinical parameters cerebrospinal fluid white blood cell count (CSF wbc) and cerebrospinal fluid protein level (CSF protein) in the LS (n=29) and ANS (n=30) groups is shown. Each box plot includes the lower quartile (lower horizontal line), median (middle horizontal line), and upper quartile (upper horizontal line). Student's T-Test was used to compare the normally distributed data between the two groups, and Mann-Whitney U test was used to compare the non-normally distributed data. p values ​​≤ 0.05 were considered statistically significant. Figure 3It can be seen that the expression level of clinical parameters such as CSF wbc in the ANS group was also significantly higher than that in the LS group, while there was no significant difference in the expression level of CSF protein in the ANS group and in the LS group, which was consistent with clinical observations.

[0077] Therefore, the present inventors further clarified the ability of these soluble factors and clinical parameters to distinguish LS from ANS patients through ROC analysis.

[0078] Table 1. Receiver operating characteristic curve analysis of CSF concentrations of soluble factors and CSF clinical parameters (CSF wbc and CSF protein).

[0079]

[0080] As can be seen from Table 1, there are significant differences in the expression levels of IL-12p70, IL-10, TNF-α, IP-10, IL-8, RANTES and GRO-α in patients with latent syphilis and in patients with asymptomatic neurosyphilis (all p values ​​are less than 0.05). Moreover, since the AUCs of these soluble factors are all greater than 0.7, they can be effectively used to distinguish patients with latent syphilis from patients with asymptomatic neurosyphilis. It should be understood that the larger the AUC, the higher the diagnostic accuracy when used for latent syphilis and asymptomatic neurosyphilis, and the more diagnostic value. Therefore, the soluble factor can be selected from any one of IL-12p70, IL-10, TNF-α, IP-10, IL-8, RANTES and GRO-α, or a combination of any two or more thereof. Preferably, the soluble factor can be selected from any one of IL-12p70, IL-10, TNF-α, IP-10, IL-8 and RANTES, or a combination of any two or more thereof. More preferably, the soluble factor is any one, any two or all three selected from IL-12p70, IL-10 and TNF-α. Further preferably, the soluble factor is IL-12p70 and / or IL-10. Even further preferably, the soluble factor is IL-12p70.

[0081] In addition, it can be seen from Table 1 that cerebrospinal fluid leukocyte count can be used to distinguish asymptomatic neurosyphilis from other syphilis such as latent syphilis, but cerebrospinal fluid protein cannot be used for the distinction.

[0082] The inventors further randomly selected 41 patient sample measurement data from the above 59 patient sample measurement data as the test group, and the remaining 18 patient sample data as the verification group (the ratio of the number of samples in the test group and the verification group was 7:3). The Cut-off values ​​of IL-10, IL-8 and CSF wbc were calculated using the 41 sample measurement data of the test group, and then the Cut-off values ​​were used to judge the remaining 18 patient sample measurement data (the random grouping operation was repeated 2 times), and the sensitivity, specificity and accuracy results are shown in Table 2 below.

[0083] Table 2. Sensitivity, specificity, and accuracy of partial factorial group validation.

[0084] factor Random number Sensitivity Specificity Accuracy IL-10 1 0.777777778 0.888888889 0.833333333 2 0.833333333 0.916666667 0.888888889 IL-8 1 0.714285714 0.909090909 0.833333333 2 0.714285714 0.818181818 0.777777778 CSF wbc 1 1 0.75 0.888888889 2 1 0.727272727 0.833333333

[0085] From the data in Table 2, it can be seen that IL-10, IL-8 and CSF wbc can be effectively used to distinguish patients with latent syphilis from patients with asymptomatic neurosyphilis. Among them, CSF wbc has the highest sensitivity, but its specificity is lower than that of IL-10 and IL-8. The accuracy of the three is basically the same.

[0086] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. Use of soluble factors and cerebrospinal fluid leukocyte counts in the preparation of a product for detecting asymptomatic neurosyphilis, characterized in that: The soluble factor is selected from any one or a combination of any two or more of IL-12p70, IL-10, and IL-8.

2. The use according to claim 1, characterized in that: The soluble factor is also selected from any one or a combination of any two or more of TNF-α, IP-10, RANTES and GRO-α.

3. The use according to claim 1, characterized in that: The product is any one of a test kit, a detection chip and a detection array.

4. The use according to claim 3, characterized in that: The kit includes a factor detection reagent for detecting the concentration of the soluble factor in cerebrospinal fluid; The detection chip is a detection chip loaded with at least the factor detection reagent; The detection array is a detection array loaded with at least the factor detection reagent.

5. The use according to claim 4, characterized in that: The factor detection reagent is an antibody or antibody pair against the corresponding soluble factor; Preferably, the antibody is a monoclonal antibody against the corresponding soluble factor.

6. The use according to claim 5, characterized in that: The antibody pair consists of a combination of a coating antibody for detecting the corresponding soluble factor and a detection antibody.

7. The use according to any one of claims 3 to 6, characterized in that: The kit further comprises a leukocyte detection reagent for detecting the leukocyte count of cerebrospinal fluid; or The detection chip or the detection array is independently further loaded with a leukocyte detection reagent for detecting the leukocyte count of cerebrospinal fluid.

8. An assessment system for determining a patient's risk of asymptomatic neurosyphilis, characterized in that: The evaluation system includes a detection module and a judgment module; wherein: The detection module is used to detect the cerebrospinal fluid concentration of soluble factors; the judgment module includes a readable carrier storing evaluation rules; The evaluation rule is: when the cerebrospinal fluid concentration of the soluble factor is detected to be higher than the corresponding cutoff value, the syphilis patient is evaluated as having a high risk of suffering from asymptomatic neurosyphilis; otherwise, the syphilis patient is evaluated as having a low risk of suffering from asymptomatic neurosyphilis; The soluble factor is selected from any one or a combination of any two or more of IL-12p70, IL-10, and IL-8.

9. The evaluation system according to claim 8, characterized in that: The soluble factor is also selected from any one or a combination of any two or more of TNF-α, IP-10, RANTES and GRO-α.

10. The evaluation system according to claim 8 or 9, characterized in that: The detection module further has the ability to detect the leukocyte count in cerebrospinal fluid.

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