Patent Application
20190361023
The present invention relates to a method and an apparatus for providing information on encephalitis related diseases. More specifically, the present invention relates to TRAIL-based encephalitis differentiation diagnosis.
Encephalitis is a neurologic disorder that can lead to severe late disorders if accurate diagnosis and appropriate treatment are not performed exactly. Encephalitis can be divided into infectious encephalitis and autoimmune encephalitis.
Infectious encephalitis can be caused by a wide variety of causative strains such as bacteria, viruses, fungi, and the like, and only therapeutic agents for some causative strains of them are present. It takes a long time to diagnose infectious encephalitis, and there is a problem that the diagnosis rate for pathogenic bacteria is only about 50%.
Autoimmune encephalitis is a newly diagnosed disease within the recent about 10 years, which is a 20-30% of total encephalitis patients. In the case of autoimmune encephalitis, autoimmune encephalitis is usually diagnosed by autoantibody detection. However, there are various types of causative strains and new antibodies are continuously discovered. Therefore, it is difficult to diagnose autoimmune encephalitis by conventional antibody test kit alone.
As such, existing diagnostic methods have difficulties in discriminating and accurately diagnosing infectious encephalitis and autoimmune encephalitis. Therefore, there is an acute need for a method and apparatus for providing information related to encephalitis diseases with faster and more accurately.
Accordingly, it is an object of the present invention to provide a method and apparatus for providing information on autoimmune encephalitis and viral encephalitis disorder more accurately.
In order to achieve the above object, according to an embodiment of the present invention, it is characterized in that an information providing method according to an embodiment of the present invention comprises the steps of:
acquiring a biological sample separated from a specimen,
identifying concentration of a protein, TNF-related apoptosis-inducing ligand (TRAIL) in the cerebrospinal fluid from the said biological sample,
comparing the concentration of the said identified TRAIL to a reference value, and
providing information related to encephalitis disorder according to the said results of comparison.
Furthermore, the said comparing step may further include a steps of discriminating the possibility of an autoimmune encephalitis disorder if the concentration of the identified TRAIL is less than a reference value according to the result of the comparison; and discriminating the possibility of a viral encephalitis disorder if the concentration of the identified TRAIL is greater than a reference value according to the result of the comparison.
Furthermore, according to another embodiment of the present invention, the said information providing method may further comprise the steps of providing viral encephalitis diagnostic information according to the viral encephalitis disorder possibility discrimination, and providing autoimmune encephalitis diagnostic information according to the autoimmune encephalitis disorder possibility discrimination.
Furthermore, the step of discriminating the possibility of autoimmune encephalitis disorder may comprise a step of discriminating between anti-NMDA receptor encephalitis and LGI1 encephalitis according to the said identified TRAIL concentration.
Furthermore, when the concentration of the TRAIL is lower than a predetermined value, it may further comprise a step of discriminating with normal without encephalitis.
Furthermore, the step of discriminating the possibility of the viral encephalitis disorder may comprise a step of discriminating Japanese Encephalitis virus (JEV) encephalitis and Herpesviridae encephalitis according to the said identified TRAIL concentration.
Furthermore, the concentration of TRAIL in the cerebrospinal fluid may be characterized by being obtained from an enzyme immunoassay (ELISA).
The apparatus for providing information according to an embodiment of the present invention includes a data input unit for receiving data including a concentration of TRAIL (TNF-related apoptosis-inducing ligand), Which is a protein in cerebrospinal fluid obtained from a biological sample, a data comparing unit for comparing the said concentration of TRAIL with the reference value, and an information providing unit for providing information related to encephalitis disorder according to the said comparison result.
Furthermore, the said information providing unit may provide information related to an autoimmune encephalitis disorder when the concentration of the RAIL is lower than a reference value according to the said results of comparison, and provide information related to a viral encephalitis disorder when the concentration of the TRAIL is greater than a reference value according to the said results of comparison.
Furthermore, the said information related to a viral encephalitis disorder may include the diagnostic information according to discrimination of the possibility of a viral encephalitis disorder, and the said information related to an autoimmune encephalitis disorder may include the diagnostic information according to discrimination of the possibility of a autoimmune, encephalitis disorder.
Furthermore, it is characterized in that the said information providing unit may distinguish between the anti-NMDA receptor encephalitis and the LGI1 encephalitis according to the said results of comparison.
Furthermore, the said information providing unit can distinguish JEV (Japanese Encephalitis virus) encephalitis and Herpesviridae encephalitis according to the said results of comparison.
Being constituting as the above, the method and apparatus for diagnosing encephalitis according to the present invention has an effect that can discriminate between viral encephalitis and autoimmune encephalitis using a TNF-related apoptosis-inducing ligand (TRAIL) in cerebrospinal fluid so that it possible to provide information related to encephalitis disorder more exactly and rapidly. Thereby, the encephalitis treatment according to the cause can be performed promptly so that it is possible to treat the encephalitis more effectively.
The effects of the present invention described above are merely one of various effects according to the present invention, and the present invention can be realized in various forms according to the application mode of the embodiment.
The combustion promoter according to the present invention will now be described by way of example only, with reference to the accompanying drawings, in which:
Hereinafter, preferred embodiments of the present invention will be described in detail. The foregoing objects, features and advantages of the present invention will become more apparent from the following detailed description taken in conjunction with the accompanying figures. Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying figures. Like reference numerals designate like elements throughout the specification. Furthermore, in the following description, the well-known functions or constructions are not described in detail to avoid obscuring the subject matter of the present invention.
A method for providing information according to an embodiment of the present invention may comprise the steps of:
acquiring a biological sample separated from a specimen,
identifying concentration of a protein, TNF-related apoptosis-inducing ligand (TRAIL) in the cerebrospinal fluid from the said biological sample,
comparing the concentration of the said identified TRAIL to a reference value, and
providing information related to encephalitis disorder according to the said results of comparison.
Furthermore, the said comparing step may further include a steps of discriminating the possibility of an autoimmune encephalitis disorder if the concentration of the identified TRAIL is less than a reference value according to the result of the comparison; and discriminating the possibility of a viral encephalitis disorder if the concentration of the identified TRAIL is greater than a reference value according to the result of the comparison.
Furthermore, according to another embodiment of the present invention, the said information providing method may further comprise the steps of providing viral encephalitis diagnostic information according to the viral encephalitis disorder possibility discrimination, and providing autoimmune encephalitis diagnostic information according to the autoimmune encephalitis disorder possibility discrimination.
Furthermore, the step of discriminating the possibility of autoimmune encephalitis disorder may comprise a step of discriminating between anti-NMDA receptor encephalitis and LGI1 encephalitis according to the said identified TRAIL concentration.
Furthermore, when the concentration of the TRAIL is lower than a predetermined value, it may further comprise a step of discriminating with normal without encephalitis.
Furthermore, the step of discriminating the possibility of the viral encephalitis disorder may comprise a step of discriminating Japanese Encephalitis virus (JEV) encephalitis and Herpesviridae encephalitis according to the said identified TRAIL concentration.
Furthermore, the concentration of TRAIL in the cerebrospinal fluid may be characterized by being obtained from an enzyme immunoassay (ELISA).
The apparatus for providing information according to an embodiment of the present invention includes a data input unit for receiving data including a concentration of TRAIL (TNF-related apoptosis-inducing ligand), which is a protein in cerebrospinal fluid obtained from a biological sample, a data comparing unit for comparing the said concentration of TRAIL with the reference value, and an information providing unit for providing information related to encephalitis disorder according to the said comparison result.
Furthermore, the said information providing unit may provide information related to an autoimmune encephalitis disorder when the concentration of the TRAIL is lower than a reference value according to the said results of comparison, and provide information related to a viral encephalitis disorder when the concentration of the TRAIL is greater than a reference value according to the said results of comparison.
Furthermore, the said information related to a viral encephalitis disorder may include the diagnostic information according to discrimination of the possibility of a viral encephalitis disorder, and the said information related to an autoimmune encephalitis disorder may include the diagnostic information according to discrimination of the possibility of a autoimmune encephalitis disorder.
Furthermore, it is characterized in that the said information providing unit may distinguish between the anti-NMDA receptor encephalitis and the LGI1 encephalitis according to the said results comparison.
Furthermore, the said information providing unit can distinguish JEV (Japanese Encephalitis virus) encephalitis and Herpesviridae encephalitis according to the said results of comparison.
For the examples of the present invention, TRAIL enzyme immunoassay (ELISA) was performed using a stored cerebrospinal fluid of 10 control subjects which have not encephalitis, 10 autoimmune encephalitis confirmed patients, and 10 viral encephalitis confirmed patients (Human TRAIL/TNFSF10 quantikine ELISA Kit, R&D System). At this time, all used cerebrospinal fluid (CSF) is initial CSF before suspected encephalitis patients start treatment by visiting.
On the other hand, in 10 patients confirmed with autoimmune encephalitis, 5 patients with anti-NMDA receptor encephalitis and 5 patients with LGI1 encephalitis were enrolled. In 10 patients confirmed with viral encephalitis, 2 patients with Varicella Zoster Virus encephalitis, 2 patients with Herpes Simplex Virus type 2 encephalitis, 1 patient with CytoMegaloVirus encephalitis, and 5 patients with Japanese Encephalitis virus encephalitis were enrolled.
1. Analysis of TRAIL Concentration in Cerebrospinal Fluid.
Referring for
2. Mean Analysis of TRAIL Concentration in Cerebrospinal Fluid Between Groups.
The Mean, Standard Deviation (SD) and Standard Error of Mean (SEM) for TRAIL concentrations in cerebrospinal fluid of the control group, the autoimmune encephalitis confirmed group, and the viral encephalitis confirmed group were described in Table 1 below.
Referring for the above Table 1, it can be confirmed that the mean value of TRAIL concentration in the cerebrospinal fluid of the control group was 2.04 pg/ml and lower than the mean value of the autoimmune encephalitis confirmed group (5.08 pg/ml) and the mean value of the viral encephalitis confirmed group (49.42 pg/ml). At this time, in case of the control group, the standard deviation was 1.99 pg/ml, the standard error of the mean was 0.63 pg/ml. And, in case of the autoimmune encephalitis confirmed group, the standard deviation was 3.08 pg/ml, the standard error of the mean was 0.97 pg/ml, and in case of the viral encephalitis confirmed group, the standard deviation was 59.57 pg/ml, the standard error of the mean was 18.84 pg/ml.
From above Table 1 and
3. Analysis of TRAIL Concentrations Mean in Cerebrospinal Fluid Between Subdivided Groups.
The below Table 2 describes Mean, Standard Deviation (SD) and Standard Error of Mean (SEM) of TRAIL concentrations in the cerebrospinal fluid of control subject groups, patient groups with anti-NMDA receptor encephalitis (NMDA), patient groups with LGI1 encephalitis (LGI1), patient groups with Japanese encephalitis virus encephalitis (JEV), and patient groups with Herpesviridae encephalitis (Herpesviridae).
Referring for the above Table 2, it can be confirmed that the mean value of TRAIL concentration in the cerebrospinal fluid was 2.04 pg/ml in the control group, 4.62 pg/ml in the NMDA receptor encephalitis patient group, 5.55 pg/ml in the LGI1 encephalitis patient group, 12.14 pg/ml in the Japanese Encephalitis virus encephalitis patient group, 86.70 pg/ml in Herpesviridae encephalitis patient group, indicating that the mean value of TRAIL concentration in cerebrospinal fluid was different according to the cause of encephalitis. At this time, it can be also confirmed that the standard deviation and the standard error of the mean were 1.99 pg/ml and 0.63 pg/ml in the control group, 0.97 pg/ml and 0.43 pg/ml in the anti-NMDA receptor encephalitis patient group, 4.46 pg/ml and 1.99 pg/ml in the LGI1 encephalitis patient group, 6.98 pg/ml and 3.12 pg/ml in the Japanese Encephalitis virus encephalitis patient group, 66.79 pg/ml and 29.87 pg/ml in Herpesviridae encephalitis patient group, respectively.
From above Table 2 and
4. Receiver Operating Characteristic (ROC) Analysis.
ROC Curve (Receiver Operating Characteristic Curve) means recipient manipulation characteristic, responder action characteristic, or recipient response characteristic. Sensitivity and specificity are used for ROC curve analysis. Sensitivity is a measure of how many percent of people diagnosed with the disease in the test are susceptible to disease, and specificity is a measure of how many percent of people who have not been affected are susceptible to disease.
The ROC curve of
As a result, the sensitivity and the specificity are 90% and 95%, respectively, so that viral encephalitis can be distinguished, and the AUC (Area Under the ROC Curve) value is 0.975.
The ROC curve of
As a result, the sensitivity and the specificity are 90% and 90%, respectively, so that viral encephalitis can be distinguished, and the AUC (Area Under the ROC Curve) value is 0.950.
Referring for
Referring for
In this case, the information providing apparatus related to encephalitis disorder may further include an extracting unit for extracting the ligand in the cerebrospinal fluid from the biological sample, and may also further include a concentration measuring unit for measuring the concentration of the ligand in the extracted ligand in the cerebrospinal fluid.
The data input unit 100 can input the concentration of the ligand in the cerebrospinal fluid obtained from the biological sample. The concentration data of the ligand in the cerebrospinal fluid to be inputted may be one that was measured from the concentration measuring unit. As described above, the concentration data may include TRAIL concentration information in cerebrospinal fluid based on TRAIL enzyme immunoassay (ELISA).
The data comparing unit 200 can compare the concentration of the ligand in the cerebrospinal fluid with the reference value. At this time, the reference value may correspond to the concentration value of the ligand in cerebrospinal fluid which is capable of discriminating the information related to the autoimmune encephalitis disorder or the viral encephalitis disease.
In particular, the data comparison unit 200 can set a reference value that increases in order of the anti-NMDA receptor encephalitis patient group, the LGI1 encephalitis patient group, the Japanese Encephalitis virus encephalitis patient group, and the Herpesviridae encephalitis patient group according to the mean value of TRAIL concentration in cerebrospinal fluid from the above Table 2 and
For example, the data comparison unit 200 may set a cutoff (reference value) when the TRAIL concentration in cerebrospinal fluid is greater than 8.128 pg/ml to determine whether it is an autoimmune encephalitis (for example, anti-NMDA receptor encephalitis or LGI1 encephalitis) or a viral encephalitis (for example, Japanese Encephalitis virus encephalitis or Herpesviridae encephalitis).
The information providing unit 300 may output and provide to a user the information related to the autoimmune encephalitis disorder or the viral encephalitis disorder according to the data obtained by the data comparison unit 200. For example, information related to an autoimmune encephalitis disorder or information related to a viral encephalitis disorder may include the above discrimination result.
At this time, the information providing unit 300 may further include a display unit, and the said display unit may include various types of screen output means such as a liquid crystal display, a thin layer transistor liquid crystal display, an organic light emitting diode, a flexible display, a three-dimensional display.
As such, it will be understood that the technical scope of the present invention can be embodied in other specific forms without departing from the spirit or essential characteristics of the present invention.
Although the present invention has been particularly shown and described with reference to exemplary embodiments thereof for illustrative purposes, it is clearly understood that the same is by way of illustration and example only and is not to be construed to the preferred embodiments of the present invention, and that various modifications, additions and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanied claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 10-2016-0118262 | Sep 2016 | KR | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/KR2017/010022 | 9/13/2017 | WO | 00 |
