WO2016129631A1 - Procédé et kit pour détecter la maladie de kawasaki - Google Patents

Procédé et kit pour détecter la maladie de kawasaki Download PDF

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WO2016129631A1
WO2016129631A1 PCT/JP2016/053940 JP2016053940W WO2016129631A1 WO 2016129631 A1 WO2016129631 A1 WO 2016129631A1 JP 2016053940 W JP2016053940 W JP 2016053940W WO 2016129631 A1 WO2016129631 A1 WO 2016129631A1
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kawasaki disease
binding protein
level
determined
subject
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Japanese (ja)
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弥生 堀内
雅亮 森
平野　久
俊平 横田
洋子 齋藤
真央 明田川
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Yokohama City University
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Priority to KR1020177018683A priority patent/KR20170115039A/ko
Publication of WO2016129631A1 publication Critical patent/WO2016129631A1/fr
Priority to US15/659,815 priority patent/US20170322228A1/en
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2400/00—Assays, e.g. immunoassays or enzyme assays, involving carbohydrates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/32—Cardiovascular disorders
    • G01N2800/328—Vasculitis, i.e. inflammation of blood vessels

Definitions

  • the present invention relates to a test method and kit for Kawasaki disease.
  • Kawasaki disease is an acute febrile rash disease mainly seen in infants under 4 years of age, and the main condition is systemic vasculitis.
  • the diagnosis of Kawasaki disease consists of several major symptoms (1.5 days or more of fever, 2. hyperemia of the conjunctiva of the eyeballs, 3. redness of the lips, tongue, 4. irregular rash, 5. stiffness of the fingers in the acute phase, palmarity. And erythema of the sole of the foot, membrane-like desquamation after antipyretic, 6. non-suppurative lymphadenopathy of the cervix) (guideline for diagnosis of Kawasaki disease).
  • the white blood cell count, C-reactive protein, hepatocyte escape enzyme, increased red sediment, leukocyte fraction (neutrophil ratio), etc. are examined, and coronary artery lesions detected by tomographic echocardiography or cardiovascular angiography Confirmation is also performed.
  • Kawasaki disease is a disease that resolves spontaneously, but if not treated, 25-30% of patients suffer from cardiac complications typified by coronary artery lesions. Therefore, in Kawasaki disease, it is important to start treatment early in the onset to calm the inflammation, and it is necessary to shorten the fever period even one day and prevent the occurrence of cardiac complications.
  • the etiology and onset mechanism of Kawasaki disease are still unknown, there are no specific diagnostic tests, there are individual differences in major symptoms, and there are many cases that do not meet the diagnostic criteria. Therefore, a rapid definitive diagnosis of Kawasaki disease is difficult.
  • Patents relating to the diagnosis of Kawasaki disease include a method of measuring blood VEGF (vascular endothelial growth factor) concentration (Patent Document 1: Japanese Patent Laid-Open No. 11-6832), one or more superantigens There are methods for measuring IgM (Patent Document 2: Japanese Patent Laid-Open No. 3-139294) and other gene polymorphism investigations (Patent Document 3: Japanese Patent Laid-Open No. 2009-72193), which are actually used in clinical practice. There is nothing yet.
  • VEGF vascular endothelial growth factor
  • the object of the present invention is to provide a method and a kit for quickly and simply examining Kawasaki disease.
  • lipopolysaccharide binding protein Lipopolysaccharide binding protein (LBP)
  • LBP leucine-rich ⁇ 2-glycoprotein 1
  • AGT angiotensinogen
  • RBP4 retinol binding protein 4
  • the gist of the present invention is as follows. (1) measuring at least one component selected from the group consisting of lipopolysaccharide binding protein, leucine-rich ⁇ 2-glycoprotein, angiotensinogen and retinol binding protein 4 in a subject-derived specimen, Test method for Kawasaki disease. (2) If at least one component selected from the group consisting of lipopolysaccharide-binding protein, leucine-rich ⁇ 2-glycoprotein, and angiotensinogen has a high level in the subject-derived specimen, the patient is suffering from Kawasaki disease The method according to (1), wherein it is determined that the possibility is high, and when the level is low, it is determined that the possibility of suffering from Kawasaki disease is low.
  • Retinol-binding protein 4 is determined to have a high possibility of suffering from Kawasaki disease when the level in the subject-derived specimen is low, and is suffering from Kawasaki disease when the level is high
  • the method according to (1) wherein the possibility is determined to be low.
  • the subject is a patient undergoing treatment for Kawasaki disease, and at least one component selected from the group consisting of lipopolysaccharide binding protein, leucine-rich ⁇ 2-glycoprotein, and angiotensinogen is present in the subject-derived specimen Is measured once or multiple times at different times, and when the level is low or decreased, it is determined that treatment has recovered from Kawasaki disease.
  • the method according to (1) wherein it is determined that recovery has not been performed or recovery has been insufficient.
  • Reagent capable of specifically detecting lipopolysaccharide-binding protein, reagent capable of specifically detecting leucine-rich ⁇ 2-glycoprotein, reagent capable of specifically detecting angiotensinogen and retinol-binding protein 4 can be specifically detected
  • a test kit for Kawasaki disease comprising at least one reagent selected from the group consisting of reagents.
  • Kawasaki disease About 10,000 patients are diagnosed with Kawasaki disease each year. The number of other children with febrile illnesses of unknown cause is also very large, and the market scale will be large if Kawasaki disease is diagnosed as an initial screening test for these patients. In addition, if it can be applied to the determination of severity, it is possible to avoid the use of expensive gamma globulin preparations as a therapeutic agent, leading to savings in medical costs.
  • Kawasaki disease can be diagnosed promptly with a very high probability by an inspection method with a small patient burden in addition to diagnosis by main symptoms.
  • the therapeutic effect of Kawasaki disease can be confirmed.
  • This specification includes the contents described in the specification and / or drawings of Japanese Patent Application No. 2015-024506, which is the basis of the priority of the present application.
  • the vertical axis indicates the serum protein concentration. ***: p ⁇ 0.001, **: p ⁇ 0.01, *: p ⁇ 0.1, NS: non-significant Changes in LBP, LRG1, AGT, and RBP4 based on ELISA results. Fluctuation in the expression level between the acute and convalescent stages of Kawasaki disease and other healthy children (during allergy testing) in the same 42 patients.
  • the vertical axis indicates the serum protein concentration, and the acute phase and the recovery phase are connected by a line.
  • sensitivity% percentage that is positive when people who are truly Kawasaki disease are tested
  • 100% -specificity% proportion of misdiagnosing diseases other than Kawasaki disease as Kawasaki disease
  • the present invention includes measuring the level in a subject-derived specimen for at least one component selected from the group consisting of lipopolysaccharide binding protein, leucine-rich ⁇ 2-glycoprotein, angiotensinogen and retinol binding protein 4. , Provide a test method for Kawasaki disease.
  • At least one component selected from the group consisting of lipopolysaccharide binding protein, leucine-rich ⁇ 2-glycoprotein, and angiotensinogen has a high level in the subject-derived specimen, it may be affected by Kawasaki disease When it is determined that the level is high and the level is low, it can be determined that the possibility of suffering from Kawasaki disease is low.
  • the present inventors have confirmed that many of these proteins are expressed in the acute phase of Kawasaki disease (see Examples described later).
  • Retinol-binding protein 4 is judged to have a high possibility of suffering from Kawasaki disease when the level in the sample derived from the subject is low, and may be suffering from Kawasaki disease when the level is high Can be determined to be low.
  • the present inventors have confirmed that the expression of this protein is decreased in the acute phase of Kawasaki disease (see Examples described later). Therefore, the method of the present invention can be used for diagnosis of Kawasaki disease (determination of presence or absence of Kawasaki disease).
  • the cut-off value (acute vs control) in Table 1 below in Examples described later can be used to determine whether or not to have Kawasaki disease, in particular, to make a diagnosis by distinguishing from other diseases.
  • LBP lipopolysaccharide binding protein
  • LRG1 leucine-rich ⁇ 2-glycoprotein
  • angiotensinogen when the serum concentration is 68.83 ⁇ g / mL (concentration when the specificity is 95%) or more, it is determined that there is a high possibility of suffering from Kawasaki disease.
  • the concentration is less than 68.83 ⁇ g / mL, it can be determined that the possibility of suffering from Kawasaki disease is low.
  • retinol binding protein 4 RBP4
  • the above cut-off value is best when the specificity is 95% based on the ROC curve, better when the specificity is 90%, and when the specificity is 80%. You may change the time as good.
  • the subject is a patient undergoing treatment for Kawasaki disease
  • at least one component selected from the group consisting of lipopolysaccharide binding protein, leucine-rich ⁇ 2-glycoprotein, and angiotensinogen is contained in the subject-derived specimen. Is measured once or multiple times at different times, and when the level is low or decreased, it is determined that treatment has recovered from Kawasaki disease. It can be determined that no recovery has occurred or recovery is insufficient. The present inventors compared the acute phase and the recovery phase of Kawasaki disease, and confirmed that these proteins decreased with the recovery (see Examples described later).
  • the level in the subject-derived sample was measured once or multiple times at different times, and when the level was high or increased, it was determined that the treatment recovered from Kawasaki disease, and the level was When it is low or does not rise, it can be determined that treatment has not recovered from Kawasaki disease or recovery is insufficient.
  • the present inventors compared the acute phase and the recovery phase of Kawasaki disease, and confirmed that these proteins increased with the recovery (see Examples described later). Therefore, the method of the present invention can also be used for changes in the pathology of patients with Kawasaki disease, current pathological conditions, prognosis tests, and confirmation of the therapeutic effects of Kawasaki disease.
  • the cut-off value (acute vs recovery) shown in Table 1 below in Examples described later can be used.
  • the subject is a patient undergoing treatment for Kawasaki disease, for lipopolysaccharide binding protein (LBP)
  • the serum concentration in the subject-derived specimen is measured once or multiple times at different times, and the serum concentration is 56.54 ⁇ g / mL (concentration at 95% specificity) or less
  • the serum concentration is 56.54 ⁇ g / mL (concentration at 95% specificity) or less
  • LRG1 leucine-rich ⁇ 2-glycoprotein
  • the serum concentration in the subject-derived specimen is measured once or multiple times at different times, and the serum concentration is 369.7 ⁇ g / mL (concentration when the specificity is 95%) )
  • AGT angiotensinogen
  • the serum concentration in the sample derived from the subject is measured once or multiple times at different times, and the serum concentration is 101.9 ⁇ g / mL (concentration when the specificity is 95%) or less.
  • the serum concentration in the subject-derived specimen is measured once or multiple times at different times, and the serum concentration is 6.759 ⁇ g / mL (concentration when the specificity is 95%) or more Is determined to have recovered from Kawasaki disease by treatment, and if the serum concentration is lower than 6.759 ⁇ g / mL, it is determined that treatment has not recovered from Kawasaki disease or recovery is insufficient be able to.
  • the above cut-off value is best when the specificity is 95% based on the ROC curve, better when the specificity is 90%, and when the specificity is 80%. You may change the time as good.
  • test subject-derived specimens include serum and whole blood.
  • the present invention specifically detects a reagent that can detect lipopolysaccharide-binding protein, a reagent that can specifically detect leucine-rich ⁇ 2-glycoprotein, a reagent that can specifically detect angiotensinogen, and a retinol-binding protein 4 specifically.
  • a test kit for Kawasaki disease comprising at least one reagent selected from the group consisting of possible reagents.
  • an antibody is preferable, an antibody that specifically binds to a lipopolysaccharide-binding protein, an antibody that specifically binds to leucine-rich ⁇ 2-glycoprotein, an antibody that specifically binds to angiotensinogen, and retinol-binding protein 4 It may be an antibody that specifically binds.
  • Such antibodies are commercially available and can be used.
  • the antibody may be either a monoclonal antibody or a polyclonal antibody.
  • the antibody may be labeled with a radioisotope, enzyme, luminescent material, fluorescent material, biotin, and the like.
  • a target molecule In the case of detecting a target molecule by reacting a primary antibody that specifically binds to a target molecule (in the present invention, LBP, LRG1, ATG, RBP4) and then reacting with a secondary antibody that binds to the primary antibody.
  • a primary antibody that specifically binds to a target molecule in the present invention, LBP, LRG1, ATG, RBP4
  • a secondary antibody that binds to the primary antibody In some cases, the secondary antibody is labeled (the primary antibody is not labeled).
  • kit of the present invention includes a standard protein (LBP, LRG1, ATG, RBP4), buffer, substrate (when antibody is enzyme-labeled), reaction stop solution, washing solution, reaction vessel, instruction manual, etc. May be included.
  • a standard protein LBP, LRG1, ATG, RBP4
  • buffer when antibody is enzyme-labeled
  • reaction stop solution washing solution
  • reaction vessel instruction manual, etc. May be included.
  • Example 1 Two types of protein using serum from 55 acute cases of Kawasaki disease and 51 cases of convalescence (provided by Yokohama City University Hospital, Yokohama City University Hospital, Kanagawa Children's Medical Center, Public Showa Hospital) The following operations were performed.
  • the PVDF membrane after blocking treatment was diluted with an antibody dilution buffer (anti-LBP antibody (GeneTex) diluted 3,000 times, anti-LRG1 [EPR 12362] antibody (abcam) diluted 5,000 times) and 16 times at room temperature. The reaction was allowed for ⁇ 18 hours. After the reaction, each PVDF membrane was washed with TBS (TBS-T) containing 0.05% [v / v] Tween 20 for 10 minutes three times, and diluted to 5,000 times with a buffer for antibody dilution. React with HRP at room temperature for 1 hour. After the reaction, it was washed again with TBS-T for 10 minutes three times, and detected with LAS-4000 EP UV mini PRH (Fuji Film) using ECL Select Western Blotting Detection Reagent (GE Healthcare) as a substrate.
  • an antibody dilution buffer anti-LBP antibody (GeneTex) diluted 3,000 times, anti-LRG1 [EPR 12362] antibody (abcam
  • MultiGauge ⁇ ⁇ ⁇ Analysis Software digitizes the intensity of the band, and commercially available recombinant protein (Recombinant Human LBP (R & D Systems) [2.5 ng], Recombinant Human LRG1 Novoprotein) [10 ng]) was used as a standard protein for quantitative analysis, and the relative amount of each band was calculated when the intensity of the standard protein band was taken as 100.
  • the obtained numerical values were graphed, and Mann-Whitney test was performed in the acute phase and the recovery phase using GraphPad Prism (ver. 5, MDF).
  • LBP lipopolysaccharide
  • LBP has been reported to be upregulated in febrile urinary tract infection and sepsis [Pediatric Nephrology, 28, 1091-1097, 2013.]. Therefore, it was considered that bacteria and the like were also infected in Kawasaki disease, and as a result, the expression of LBP increased.
  • LRG1 is also present in blood and has been identified as a novel inflammatory marker protein, and it has been reported that its expression increases due to rheumatoid arthritis, cancer, inflammatory bowel disease, macrophage activation by LPS administration, etc. [Annals of the Rheumatic Diseases, 69: 770-774, 2010., Biochem Biophys Res Commun, 382: 776-779, 2009., Proc Natl Acad Sci U S A. 110, E2332-E2341,2013.]. In recent years, it has been reported that angiogenesis is promoted through the regulation of transforming growth factor- ⁇ (TGF- ⁇ ) signaling [Nature, 499: 306-311, 2013.].
  • TGF- ⁇ transforming growth factor- ⁇
  • TGF- ⁇ is also involved in the expression of VEGF, and VEGF is said to be present in high concentrations in the serum of patients with acute Kawasaki disease [Pediatric Research, 44: 596-599, 1998.].
  • VEGF is said to be present in high concentrations in the serum of patients with acute Kawasaki disease
  • inflammation and angiogenesis are seen in coronary aneurysms and myocardium in patients with Kawasaki disease [Pediatric Cardiology, 26: 578-584, 2005.]. Therefore, it is suggested that LRG1 may be involved in coronary aneurysm formation in the myocardium or inflammation in the myocardium.
  • LBP and LRG1 have high concentrations in blood and can be easily detected. Therefore, by using the expression level of these two proteins, both of which are the criteria for diagnosis, in addition to diagnostic methods based on major symptoms that are influenced by the subjectivity and experience of doctors and may be missed or missed, it is accurate and prompt. I think there is a possibility of diagnosis.
  • Example 2 Serum of 20 patients with Kawasaki disease acute phase and 20 cases of recovery phase (provided by Yokohama City University Hospital, Yokohama City University Hospital, Kanagawa Children's Medical Center, Public Showa Hospital) The following operations were performed.
  • the PVDF membrane subjected to the blocking treatment was reacted with Anti-AGT antibody (IBL) diluted 100 times with an antibody dilution buffer at room temperature for 16 to 18 hours. After the reaction, each PVDF membrane was washed with TBS-T for 10 minutes three times, and reacted with standard anti-mouse IgG-HRP diluted 5,000 times with an antibody dilution buffer at room temperature for 1 hour. After the reaction, it was washed again with TBS-T for 10 minutes three times, and detected with LAS-4000 EP UV mini PRH using ECL Select Western Blotting Detection Reagent as a substrate.
  • IBL Anti-AGT antibody
  • the intensity of the band is digitized from the obtained image by MultiGauge Analysis Software, and the obtained numerical value is graphed, and the Mann-Whitney test in the acute phase and the recovery phase using GraphPad Prism (ver. 5, MDF) Went.
  • AGT is a precursor of angiotensin and decomposes into angiotensin I and II in the renin-angiotensin system.
  • AGT is increased in hypertension, diabetes, and chronic nephritis, and is considered to play an important role in the development and development of hypertension and kidney damage.
  • Kawasaki disease is not known, and is the first knowledge obtained in the present invention.
  • Example 3 Serum was provided by Yokohama City University Hospital, Kanagawa Children's Medical Center, Public Showa Hospital, National Institute of Infectious Diseases, Kobe University Hospital, Japanese Red Cross Wakayama Medical Center, Yokohama City University Citizen General Medical Center (On Table 1). All samples have received comprehensive consent from the provider.
  • Acute phase sera of Kawasaki disease patients Serum during fever of 55 patients
  • Recovery phase during recovery of Kawasaki disease patients Serum after fever of 51 patients
  • Sera from patients with viral infections G1: 106 (21 RS viruses, 23 influenza A viruses, 20 influenza B viruses, 20 rotaviruses, 7 noroviruses, 3 adenoviruses, 12 throat adenoviruses)
  • Bacterial infection sera G2: 21 (1 pneumococci, 1 pneumoniae, 1 gram-negative bacilli, 1 gram-negative bacilli, 7 streptococci, 3 E. coli, 2 S.
  • each PVDF membrane was washed with TBS-T for 3 minutes for 10 minutes, and reacted with anti-rabbit IgG-HRP or anti-mouse IgG-HRP diluted 5000 times with antibody dilution buffer for 1 hour at room temperature. I let you. After the reaction, it was washed again with TBS-T for 10 minutes three times, and photographed with LAS-4000 EP UV mini PRH using the secondary labeled antibody detection reagent as a substrate. Band intensities were quantified by MultiGauge Analysis Software.
  • Kawasaki disease related to the serum concentration of each protein obtained from the results of the ELISA method, and the significant difference test in the acute phase and recovery period of Kawasaki disease regarding the expression level in the patient serum obtained from the Western blot method results
  • the statistical difference software Graph Pad Prism was used to test the significant difference between the acute phase and each group (Kawasaki disease recovery phase, healthy children, and other pediatric diseases).
  • Kawasaki disease acute phase 55 samples
  • convalescent phase 51 samples
  • other childhood diseases other than Kawasaki disease acute phase and Kawasaki disease previously item: 144 samples
  • ROC analysis was performed to calculate AUC.
  • the AUC value of LBP was 0.8966 between Kawasaki disease acute phase and recovery phase, and 0.8497 between Kawasaki disease acute phase and other diseases, indicating that LBP is useful for diagnosis after LRG1. It was. Furthermore, the cut-off value, sensitivity, and specificity were calculated using the statistical analysis software Graph Pad Prism based on the data in FIG. 11 (bottom of Table 1). Cut-off value (best); concentration at which the specificity reaches 95%. Cut-off value (better); concentration at which specificity is 90%. Cut-off value (good): concentration at which the specificity reaches 80%. Sensitivity: The rate at which patients with true Kawasaki disease are diagnosed as positive. 100%-specificity; the rate at which patients other than Kawasaki disease are misdiagnosed as having Kawasaki disease.
  • RBP4 is an RBP produced in the liver or adipocytes and secreted into the blood (plasma), so it is also referred to as Plasma RBP (PRBP).
  • PRBP4 Plasma RBP
  • Kawasaki disease The etiology of Kawasaki disease is still unclear, and it is suggested that some abnormality in the immune system may have caused the pathology.
  • inflammatory proteins such as CRP and SAA are present in excess in the patient acute phase serum, and the serum concentration can be examined as a reference item in general blood tests.
  • many of such inflammatory proteins reflect non-specific systemic inflammation and vasculitis, and do not specifically differentiate Kawasaki disease. . Therefore, it is important to develop diagnostic markers other than such proteins that can be distinguished from other diseases.
  • Kawasaki disease can be specifically diagnosed by examining the serum levels of Kawasaki disease-related proteins LBP, LRG1, AGT, and RBP4 in patients. In particular, the diagnostic performance of LBP and LRG1 was found to be good.
  • Kawasaki disease The pathology of Kawasaki disease is very widespread, and many mechanisms are expected to be involved in the onset. Since all four types of proteins found in this study are present at high concentrations in the blood, it is considered possible to develop a simple and accurate Kawasaki disease diagnosis method using these proteins as indicators.
  • the present invention can be used for diagnosis of Kawasaki disease and confirmation of therapeutic effects.

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Abstract

La présente invention concerne un procédé et un kit permettant de détecter rapidement et simplement la maladie de Kawasaki. Le procédé pour détecter la maladie de Kawasaki consiste à mesurer le niveau d'au moins un composant choisi dans le groupe constitué d'une protéine de liaison des lipopolysaccharides, de l'alpha-2 glycoprotéine riche en leucine, d'un angiotensinogène et de la protéine 4 de liaison du rétinol dans un échantillon prélevé sur un sujet. Le kit pour détecter la maladie de Kawasaki comprend au moins un réactif choisi dans un groupe constitué d'un réactif capable de détecter spécifiquement la protéine de liaison des lipopolysaccharides, d'un réactif capable de détecter spécifiquement l'alpha-2 glycoprotéine riche en leucine, d'un réactif capable de détecter spécifiquement un angiotensinogène et d'un réactif capable de détecter spécifiquement la protéine 4 de liaison du rétinol.
PCT/JP2016/053940 2015-02-10 2016-02-10 Procédé et kit pour détecter la maladie de kawasaki Ceased WO2016129631A1 (fr)

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JP2016574830A JP6153239B2 (ja) 2015-02-10 2016-02-10 川崎病の検査方法およびキット
KR1020177018683A KR20170115039A (ko) 2015-02-10 2016-02-10 가와사키병의 검사 방법 및 키트
US15/659,815 US20170322228A1 (en) 2015-02-10 2017-07-26 Method, kit and test strip for detecting kawasaki disease

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Cited By (3)

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WO2018030270A1 (fr) * 2016-08-09 2018-02-15 公立大学法人横浜市立大学 Procédé et spécimen pour tester la maladie de kawasaki
JP2019004880A (ja) * 2017-06-28 2019-01-17 国立大学法人高知大学 新生児感染症または周産期感染症の診断技術
TWI704349B (zh) * 2019-06-17 2020-09-11 高雄榮民總醫院 蛋白質生物標記用以診斷川崎症的用途

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KR102705469B1 (ko) * 2022-05-30 2024-09-11 충남대학교산학협력단 불응성 가와사키병의 감별 진단을 위한 정보 제공 방법

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