WO2005108985A1 - Procédé d’évaluation de l'artériosclérose systémique et réactif d’évaluation - Google Patents

Procédé d’évaluation de l'artériosclérose systémique et réactif d’évaluation Download PDF

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Publication number
WO2005108985A1
WO2005108985A1 PCT/JP2005/008070 JP2005008070W WO2005108985A1 WO 2005108985 A1 WO2005108985 A1 WO 2005108985A1 JP 2005008070 W JP2005008070 W JP 2005008070W WO 2005108985 A1 WO2005108985 A1 WO 2005108985A1
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Prior art keywords
diabetic nephropathy
hasg
antibody
elastin
antibodies
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PCT/JP2005/008070
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English (en)
Japanese (ja)
Inventor
Osamu Hotta
Masahiko Katayama
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Eisai R & D Management Co., Ltd.
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Priority to JP2006512971A priority Critical patent/JP4762135B2/ja
Publication of WO2005108985A1 publication Critical patent/WO2005108985A1/fr

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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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans

Definitions

  • the present invention relates to a method for determining diabetic nephropathy and a kit used for the method. More specifically, the present invention measures the amount of elastin hydrolyzate in the circulating fluid of a subject and, based on the measured value, determines the diabetes!
  • the present invention relates to a method for determining systemic arteriosclerosis, preferably diabetic nephropathy, such as dyspnea, acute progressive glomerulonephritis, amyloidosis or cholesterol embolism, and a kit for use in the method.
  • Non-Patent Document 1 Diabetes is a group of diseases characterized by chronic hyperglycemia due to insufficient insulin action and accompanied by various characteristic metabolic abnormalities. Both genetic and environmental factors contribute to its onset. Long-term persistence of metabolic abnormalities causes unique complications and immediately promotes arteriosclerosis (Non-Patent Document 1).
  • diabetic nephropathy is one of the microvascular complications of diabetes and is an important disease that affects the prognosis of diabetic patients.
  • the number of patients with diabetic nephropathy has been steadily increasing, and the success or failure of diagnosis and treatment is not only important for the prognosis and quality of life of many diabetic patients, but also for medical economics.
  • Non-Patent Document 2 The stages of diabetic nephropathy are classified into stage 1 (early nephropathy) to stage 5 (dialysis treatment stage), and the more severe the stage, the more severe the treatment is. The need comes out.
  • Non-Patent Document 3 Diagnosis of atherosclerosis in diabetic patients has also been shown to indicate that the severity of complications correlates well with atherosclerosis.
  • diagnosis of arterial stiffness is broadly based on pulse wave velocity (PWV), etc. It is implemented in general medical institutions.
  • the pulse wave velocity measures the degree of stiffness of the blood vessel wall by measuring the velocity of the pulse wave through the blood vessel wall at a specific site (Non-Patent Document 4).
  • This diagnostic technique does not involve the collection of bodily fluids, requires the installation of special equipment that has high diagnostic reproducibility, and requires the patient to be restrained for a certain period of time.
  • Ccr indicates the amount of plasma required to excrete specific components in plasma into the kidneys and urine for a certain period of time, and it is a test item that accurately diagnoses the glomerular filtration capacity of the kidneys. Since it is necessary to restrain the patient for hours or 24 hours and it is necessary to collect urine and plasma at the same time, it lacks versatility and is difficult to perform frequently on a large number of patients.
  • urinary protein and urinary microalbumin measurement and Ccr are both indicators that mainly diagnose renal function, and may be diagnosed as positive even in renal insufficiency limited to the kidneys. It is not a specific diagnostic indicator of the disease.
  • Non-Patent Document 6 Requires a renal biopsy (Non-Patent Document 6). The problem is that renal biopsy is difficult to perform frequently because of the heavy physical burden on the patient.
  • Aortic dissection is based on arteriosclerosis and is a disease in which the blood vessel wall ruptures and detaches due to an increase in blood pressure.
  • elastin molecules which are mainly localized in the blood vessel wall, are cleaved by various proteases, Degradants are expected to appear in the circulating fluid, which will lead to increased blood levels of the degradants.
  • Non-Patent Documents 8, 11, and 12 the relationship between the concentration of elastin hydrolyzate in blood and arteriosclerosis and atherosclerosis-related diseases has been suggested.
  • Non-Patent Document 8 the relationship between the concentration of elastin hydrolyzate in blood and diabetes.
  • Non-Patent Document 13 the concentration of elastin hydrolyzate in blood increases in complications of circulatory disorders in diabetes.
  • this report showed only a tendency for a group of patients with extremely severe diabetic circulatory disorder called foot ulcers and scarring symptoms.
  • Patent Document 1 JP-A-2002-350439
  • Non-Patent Document 1 Diabetes 42, 385 (1999)
  • Non-patent document 2 Japanese clinical practice 60, 260-269 (2002)
  • Non-patent document 3 Hypertension treatment guideline 2000 edition, 55-58 (2000) Kyorinsha
  • Non-patent document 4 Japanese clinical practice 62, 80-86 (2004)
  • Non-Patent Document 5 Diabetes 44, 623 (2001)
  • Non-patent document 6 Japanese clinical practice 60, 316-322 (2002)
  • Non-Patent Document 7 Meth.EnzymoL, 163, 656-673 (1988)
  • Non-Patent Document 8 Clin.Physiol.Biochem., 8, 273-282 (1990)
  • Non-Patent Document 9 J. Immunol.Methods, 164, 175-187 (1993)
  • Non-Patent Document 10 Eur.J. Vase.Endovasc.Surg., 14, 12-16 (1997)
  • Non-Patent Document 11 Atherosclerosis, 66, 163-168 (1987)
  • Non-Patent Document 12 Eur.J. Vase.Endovasc.Surg., 24, 440-444 (2002)
  • Non-Patent Document 13 Diabetologia Croatica, 26-3, 151-155 (1997)
  • Non-Patent Document 14 Atherosclerosis, 131, 73-78 (1997)
  • Non-Patent Document 15 General Pharmacology, 35, 59-64 (2000)
  • the present invention provides a method and kit for simply and accurately determining systemic arteriosclerosis such as diabetic nephropathy, acute progressive glomerulonephritis, amyloidosis or cholesterol embolism, preferably diabetic nephropathy. To provide.
  • systemic arteriosclerosis such as diabetic nephropathy, acute progressive glomerulonephritis, amyloidosis or cholesterol embolism, preferably diabetic nephropathy.
  • the present inventors considered that among the group of diseases other than aortic dissection based on systemic atherosclerosis, there is a disease in which the measured value of elastin hydrolyzate in the blood increases. The study was conducted on diabetic patients and other related diseases.
  • the present inventors compared the elastin hydrolyzate concentration in the blood of the diabetic patient group and the diabetic nephropathy patient group, and found that the blood concentration was extremely high only in the diabetic nephropathy group. And found that measurement of the amount of elastin hydrolyzate is useful for diagnosis of diabetic nephropathy.
  • acute glomerulonephritis, membranous proliferative glomerulonephritis, and purpura nephritis! / Puta primary glomerulonephritis (renal dysfunction of the kidney-limited type) also shows that blood levels do not increase. I found it.
  • the present invention provides a method for measuring diabetic nephropathy, acute progressive glomerulonephritis, amyloidosis or cholesterol embolism, and measuring systemic arteriosclerosis, preferably diabetic nephropathy. It provides a new diagnostic index for diagnosing disease.
  • the present invention measures the amount of elastin hydrolyzate in the circulating fluid of a subject, and based on the measured value, evaluates diabetic nephropathy, acute progressive glomerulonephritis, amyloidosis or cholesterol embolism.
  • determining systemic atherosclerosis preferably diabetic nephropathy
  • the determination in the present invention includes not only determining whether or not the patient has diabetic nephropathy but also determining the severity of diabetic nephropathy.
  • the antibody is preferably a monoclonal antibody.
  • one of the antibodies is immobilized on a solid phase, and the other is labeled with a labeling substance, using the first or second monoclonal antibody.
  • Examples of the monoclonal antibody include HASG-2 (FERM BP-08488), HASG-30 (FERM BP-08488).
  • the first and second monoclonal antibodies are preferably a combination of monoclonal antibodies produced by HASG-30 and HASG-61-1 hybridomas.
  • the present invention also includes one or more antibodies having specificity and affinity for elastin hydrolyzate, measures the amount of elastin hydrolyzate in the circulating fluid of a subject, and measures the measured value. Based on the criteria for diabetic nephropathy, acute progressive glomerulonephritis, amyloidosis or cholesterol embolism, to determine systemic atherosclerosis, preferably diabetic nephropathy (Hereinafter, also referred to as “the kit of the present invention!”).
  • FIG. 1 is a standard curve showing the relationship between aortic elastin hydrolyzate concentration in a test sample and absorbance.
  • FIG. 3 Among the diabetic patient group (129 cases), 53 diabetic patients (without nephropathy), 53 diabetic nephropathy patients (51 cases), diabetic nephropathy + chronic renal failure patients (25 cases), Group 4 shows the distribution of serum elastin hydrolyzate concentration in diabetic nephropathy + dialysis therapy-introduced patients (53 patients).
  • the method of the present invention is characterized in that the amount of elastin hydrolyzate in the circulating fluid of a subject is measured, and diabetic nephropathy is determined based on the measured value.
  • the circulating fluid in the present invention refers to serum, plasma, cerebrospinal fluid, ascites, and / or ivy, or a fraction thereof, and is not particularly limited as long as it is normally collected in a medical institution or the like. However, blood samples such as serum from a subject are particularly suitable.
  • any method can be used as long as the amount of elastin hydrolyzate in the circulating fluid can be measured.
  • Examples include immunochemical methods using antibodies having specificity and affinity.
  • the immunological method is not particularly limited as long as it is a method using an antibody against an elastin degradation product, preferably a human aortic elastin degradation product, and may be a latex agglutination method, a western plot method, a sandwich method, or the like. There is a method such as a competition method, which is not particularly limited, but a sandwich ELISA method is preferable.
  • the detection method examples include a method using a radioactive substance label, a method using a fluorescent label, a method using an enzyme label, and a method using electrochemiluminescence, and are not particularly limited. Preferably, it is a safe and simple enzyme immunoassay (ELISA) or an electrochemical immunoassay.
  • ELISA enzyme immunoassay
  • the antibody used is a human aortic elastin hydrolyzate
  • the polyclonal antibody is a serum obtained by immunizing rabbits, goats, sheep, etc.
  • the antibody is purified.
  • the monoclonal antibody is mouse, rat, hamster, etc.
  • the ability to use a monoclonal antibody produced by immunizing a rodent of the present invention is preferably a monoclonal antibody!
  • the animal species used for producing the monoclonal antibody is not particularly limited, but generally, Balb / C mice are most often used.
  • Monoclonal antibodies are usually monoclonal Can be prepared in the same manner as in the preparation of the internal antibody.
  • Antibodies are not limited to fragments of Fab, Fab ', F (ab'), etc., as long as they have predetermined properties and affinity.
  • the antibody may be labeled with a labeling substance.
  • Labeling substances include those used in ordinary sandwich methods for immunologically binding two antibodies to an antigen, such as enzymes, electrochemiluminescent complexes, radioactive substances, latex, fluorescent substances, and chemical substances. Light-emitting substances, metal colloid particles and the like can be mentioned. In the present invention, enzymes or electrochemiluminescent complexes are preferred.
  • the binding between the label and the antibody can be performed according to a usual method.
  • the antibody may be immobilized on a solid phase!
  • the shape and material of the solid phase are not particularly limited, and specific examples include a microtiter plate and beads.
  • the immobilization of the antibody on the solid phase can be performed according to a usual method.
  • HASG-2 hybridoma HASG-2 (FERM BP-08488), HASG-30 (FERM BP-08489), and HASG-61-1 (FERM BP-08490).
  • HASG-2 and HASG-30 are disclosed in JP-A-2002-350439.
  • HASG-2 and HASG-30 were registered at the National Institute of Advanced Industrial Science and Technology (AIST) Patent Microorganisms Depositary Center ( ⁇ 305-8566, 1-1 Tsukuba East, Ibaraki Pref. Deposited on March 18 and assigned accession numbers FERM P-18335 and FERM P-18336.On September 18, 2003, they were transferred to the International Deposit under the Budapest Treaty, and they were transferred to FERM BP-08488 and FERM BP- It has a 08489 accession number.
  • AIST Advanced Industrial Science and Technology
  • HASG-61-1 is an independent bank Deposited at the National Institute of Advanced Industrial Science and Technology Patent and Microorganisms Depositary Center on October 8, 2002, granted the accession number FERM P-19058, and transferred to an international deposit based on the Budapest Treaty on September 18, 2003.
  • FERM BP-08490 accession number accession number.
  • Specificity for human large artery elastin hydrolyzate equivalent to any of the monoclonal antibodies produced by HASG-2, HASG-30, and HASG-61-1 And antibodies having affinity can be selected by the following methods.
  • Antibodies having the same specificity and affinity can be selected by, for example, a competition test (Antibodies A Laboratory Manual, old bpnng Harbor Laboratory (1988) p.567). Specifically, a human aortic elastin hydrolyzate, which is an antigenic substance, is dissolved at an appropriate concentration in a physiological buffer and adsorbed to a solid phase of a microplate. After performing the blocking treatment, add the antibody to be evaluated together with the enzyme-labeled HASG-2, HASG-30 or HASG-61-1 monoclonal antibody in the same amount. Antibodies with similar specificity and affinity can be selected by confirming their ability to inhibit the reaction of enzyme-labeled HASG-2, HASG-30 or HASG-61-1 monoclonal antibodies.
  • selection can be made by a peptide mapping method.
  • human aortic elastin hydrolyzate which is an antigenic substance, is separated by a high-performance liquid chromatography device or the like according to differences in molecular weight, hydrophobicity, etc., and binding to various separated elastin antigen fragments is determined by HASG-2, The specificity and affinity are evaluated by comparing with HASG-30 and HASG-61-1 monoclonal antibodies. Antibodies that react equally to the antigen fragments to which the HASG-2, HASG-30 or HASG-61-1 monoclonal antibodies react are judged to have the same specificity.
  • the human aortic elastin hydrolyzate can be obtained by the method described in Biochem. J., 61, 11-21 (1955) and can be obtained as a commercial product.
  • ELISA for elastin hydrolyzate in a biological sample
  • various methods are known as a measuring method. Particularly, a simple and highly quantitative method, such as immobilized first antibody and peroxidase, is used. A sandwich method using a second antibody labeled with an enzyme is often used. In this case, the first and second antibodies react specifically to elastin degradation products.
  • the first antibody and the second antibody desired to be used may be the same.
  • an antibody (first antibody) recognizing an aortic elastin degradation product is bound to a solid phase such as a 96-well microphone plate.
  • the solid phase may be bound by a covalent bond or a non-covalent bond.
  • adsorb a blocking protein such as milk force zein in order to reduce non-specific adsorption to the solid phase.
  • a standard aortic elastin hydrolyzate solution with a clear concentration and a test biological sample, and leave it for a certain period of time.
  • washing is performed, and then another anti-aortic elastin degradation product antibody (second antibody) labeled with an enzyme such as peroxidase is added at an appropriate concentration.
  • the complex is left to stand for a certain period of time to form a complex of the first antibody, the aortic elastin degradation product, and the second antibody on the solid phase. Thereafter, the solid phase is washed, and if the enzyme substrate or the enzyme is peroxidase, a mixed solution of hydrogen peroxide and a coloring substrate such as TMBZ is added to obtain a color by the labeling enzyme. After terminating the enzyme reaction by adding an inhibitor or the like, the absorbance of the color is measured with a device such as a plate reader. It is also possible to use a luminescent substrate instead of a chromogenic substrate. In this case, the luminescence intensity is measured instead of the absorbance.
  • the amount of aortic elastin hydrolyzate in the test solution can be known with high accuracy.
  • Various methods are known for the electrochemiluminescence immunoassay, and a particularly simple and highly quantitative method is used for the first antibody, such as an antibody immobilized on magnetic beads or a second antibody.
  • the first antibody and the second antibody which desirably react specifically with the elastin degradation product, may be the same.
  • an antibody that recognizes an aortic elastin degradation product is bound to a solid phase such as magnetic beads.
  • the solid phase may be bound by a covalent bond or a non-covalent bond.
  • adsorb blocking proteins such as milk casein to reduce non-specific binding to the solid phase.
  • the solid phase is washed and Another anti-elastin hydrolyzate antibody labeled with a chemiluminescent complex, preferably a ruthenium complex
  • the solid phase is magnetic beads, it is preferably stirred to form a complex of the first antibody, the elastin degradation product antigen and the second antibody on the magnetic beads. Thereafter, the solid phase is washed, and a current is preferably passed between the electrodes in a dedicated device to cause the chemiluminescent complex, preferably a ruthenium complex, to emit light, and the emission intensity is measured.
  • a dedicated device to cause the chemiluminescent complex, preferably a ruthenium complex, to emit light, and the emission intensity is measured.
  • HASG-30 and HASG-61-1 are desirable.
  • the determination in the present invention includes not only determination of the power of diabetic nephropathy but also determination of the severity of diabetic nephropathy.
  • the determination as to whether or not the patient has diabetic nephropathy is made based on whether or not the measured value of elastin degradation product is higher than the cutoff value.
  • the cut-off value is usually determined by measuring the concentration of elastin hydrolyzate in the blood of diabetic patients diagnosed as not having diabetic nephropathy by the conventional method, and calculating the average + 3SD (standard deviation) . In the case of measuring 55 diabetic patients described in the examples, the cutoff value was 184.9 ng / mL.
  • the highest measured value of elastin degradation in blood of a diabetic patient diagnosed as not having diabetic nephropathy may be set as the cut-off value, and diabetic nephropathy may develop. If it is possible to determine whether or not the force is applied, another value may be set as the cutoff value.
  • the cut-off value for acute progressive glomerulonephritis, amyloidosis, or cholesterol embolism can be performed in the same manner as in diabetic nephropathy, but the measurement value of a healthy individual can be used instead of a diabetic patient.
  • the measured values of elastin hydrolyzate in the blood were measured for patients with diabetes, diabetic nephropathy who progressed to diabetic nephropathy and chronic renal failure, diabetic nephropathy patients who progressed to the introduction of dialysis therapy, and diabetes mellitus. Blood elastin degradation products are used as an indicator to monitor the progression of diabetic nephropathy even after it has been determined to be diabetic nephropathy, since it increases with the severity of dyspnea. It is also possible.
  • the present inventors have found that the measured value hardly increases in diabetic patients without nephropathy, is extremely high in diabetic nephropathy patients, and is high at a positive rate, as shown in Examples described later.
  • the slip rate is also high with a high positive rate.
  • elastin degradation product concentration increased according to the severity of diabetic nephropathy, and the severity of diabetic nephropathy could be determined from the elastin hydrolyzate concentration. Therefore, by measuring the amount of elastin degradation products in the circulating fluid, systemic atherosclerosis such as diabetic nephropathy, acute progressive glomerulonephritis, amyloidosis or cholesterol embolism, preferably diabetes It is possible to determine sexual nephropathy.
  • a means capable of measuring the amount of elastin hydrolyzate in the circulating fluid for example, an antibody against elastin hydrolyzate can be used for the production of a diagnostic agent for diabetic nephropathy.
  • the kit of the present invention is characterized by containing one or more antibodies having specificity and affinity for elastin degradation products.
  • the kit measures the amount of elastin hydrolyzate in the subject's circulating fluid and uses that measurement to determine systemic arterial disease such as diabetic nephropathy, acute progressive glomerulonephritis, amyloidosis or cholesterol embolism. It is used to determine sclerosis, preferably diabetic nephropathy.
  • the antibody is as described for the method of the invention.
  • the antibodies are preferably the first and second antibodies which are preferably monoclonal antibodies. More preferably, a second monoclonal antibody is used. Further, it is preferable that one of the first and second antibodies is immobilized on a solid phase, and the other is labeled with an enzyme or an electrochemiluminescent complex. Labels and are as described for the method of the invention.
  • the antibody in the kit of the present invention may be a solution or a lyophilized antibody.
  • the kit of the present invention may contain, in addition to the first and second antibodies, reagents commonly used in immunoassays.
  • reagents commonly used in immunoassays include a standard antigen (human aortic elastin digest) solution, a substrate solution, a sample diluent, and a washing solution.
  • a standard antigen human aortic elastin digest
  • the reagents described in the method for measuring elastin degradation products described above can be used.
  • the kit of the present invention can be used according to the method of the present invention.
  • the kit of the present invention may be used as a diagnostic agent for systemic arteriosclerosis such as diabetic nephropathy, acute progressive glomerulonephritis, amyloidosis or cholesterol embolism, preferably diabetic nephropathy. Can be.
  • systemic arteriosclerosis such as diabetic nephropathy, acute progressive glomerulonephritis, amyloidosis or cholesterol embolism, preferably diabetic nephropathy.
  • Human aortic elastin hydrolyzate (Elastin Products, Cat. No .: HA587) was intraperitoneally injected into Balb / C female mice (6 weeks of age) in an amount of 0.1 mg / animal in Complete 'Freund's Adjuvant (Difco). Co., Ltd.). Three weeks later, the same amount of the human aortic elastin hydrolyzate was administered intraperitoneally together with Incomplete 'Freund's adjuvant (manufactured by Difco). Three weeks later, the mouse was administered the human aortic elastin hydrolyzate alone (0.1 mg / mouse). Three days after the end of the final immunization, the mouse spleen was also removed.
  • the excised spleen was dispersed with a mesh, cultured briefly, mixed with Sp2 / 0-Agl4 mouse myeloma cells, and the cells were added in the presence of 50% polyethylene glycol 1500 (Roche's Diagnostics). It was fused.
  • the fused hybridoma cells are placed in several 96-well microphone plate culture plates. The cells were dispersed and cultured in RPMI1640 liquid medium (Sigma-Aldrich) containing 10% fetal bovine serum and HAT reagent (Sigma-Aldrich) for 1 to 2 weeks.
  • a peroxidase-labeled secondary antibody that reacts with mouse IgG (manufactured by Dako Japan) was added at an appropriate concentration. After a certain period of time, the plate was washed, and an ABTS substrate solution (manufactured by Roche's Diagnostics) was dried. The desired monoclonal antibody-producing hybridoma was selected based on the presence or absence of color development. Each of the selected strains was crawled several times. The three strains of hybridomas thus obtained were named HASG-2, HASG-30, and HASG-61-1.
  • HASG-30 monoclonal antibody HASG-61-1 monoclonal antibody
  • the HASG-30 monoclonal antibody and HASG-61-1 monoclonal antibody prepared in section (1) were prepared as purified IgG. These monoclonal antibodies were confirmed to not compete with each other by a competition test.
  • the HASG-30 monoclonal antibody was dissolved in phosphate buffered saline (PBS) to a final concentration of 0.01 mg / mL, and 0.1 mL of the solution was added to each well of a 96-well microphone port plate (Nalge Nunc).
  • TBS Tris-buffered saline
  • Tween-TBS TBS containing 0.05% Tween-20 (manufactured by Sigma-Aldrich) (hereinafter abbreviated as Tween-TBS) Wash) three times. Then, the periodic acid method [Antibodies: a Laboratory Manual, by Ed. Harlow & D. Lane, Cold bpnng Haroor Laboratory Press]
  • the total number of diabetic patients in the first group was 53 diabetic patients (without nephropathy), 51 patients with diabetic nephropathy as the second group, and diabetic nephropathy patients who progressed to chronic renal failure as the third group ( (See below and Fig. 3 as diabetic nephropathy + chronic renal failure) 25 patients, diabetic nephropathy who progressed until the introduction of dialysis therapy as group 4 (below and diabetic nephropathy + in Fig. 3) Dialysis therapy was introduced).
  • the measured values in the sera of 108 healthy subjects were also compared with these four groups.
  • FIG. This figure is called a box-and-whisker plot.
  • Elastin degradation products were measured at 44.2 ⁇ 19.9 ng / mL for healthy subjects, 80.2 ⁇ 35.8 ng / mL for group 1 diabetes, 224.6 ⁇ 149.6 ng / mL for group 2 diabetic nephropathy, and group 3
  • the measured value was 337.8, 170.4 ng / mL
  • the measured value was 590.7 ⁇ 267.6 ng / mL, and the measured value clearly increased as the disease progressed. The result was obtained.
  • diabetic nephropathy by measuring the amount of elastin hydrolyzate in a circulating fluid such as serum, diabetic nephropathy can be obtained quickly and simply without using a special device, with a high positive rate, acute With advanced glomerulonephritis, amyloidosis or cholesterol embolism! / Patients with systemic arteriosclerosis, preferably diabetic nephropathy, and diabetic nephropathy! Can determine the severity.

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Abstract

Un produit de décomposition de l’élastine dans un fluide circulant d’un sujet est quantifié par un procédé immunologique à l’aide, par exemple, d’un anticorps ayant une spécificité et une affinité pour le produit de décomposition de l’élastine et ensuite une artériosclérose systémique comme une néphropathie diabétique, une glomérulonéphrite de progression rapide, une amylose ou une embolie par cholestérine, de préférence une néphropathie diabétique, est évaluée sur la base des données de mesure.
PCT/JP2005/008070 2004-05-06 2005-04-27 Procédé d’évaluation de l'artériosclérose systémique et réactif d’évaluation WO2005108985A1 (fr)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002537775A (ja) * 1999-02-26 2002-11-12 ハイバージェン・リミテッド 糖尿病性腎症を提示する役割を有する遺伝子の同定
JP2002350439A (ja) * 2001-05-30 2002-12-04 Eisai Co Ltd エラスチン分解物の測定方法及び測定キットならびに大動脈解離症の検出方法及び検出キット

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002537775A (ja) * 1999-02-26 2002-11-12 ハイバージェン・リミテッド 糖尿病性腎症を提示する役割を有する遺伝子の同定
JP2002350439A (ja) * 2001-05-30 2002-12-04 Eisai Co Ltd エラスチン分解物の測定方法及び測定キットならびに大動脈解離症の検出方法及び検出キット

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DAHLBAECK: "Immunohistochemical demonstration of vitronection in accociation with elastin and amyloid deposits in human kidney", HISTOCHEMISTRY, vol. 87, no. 5, 1987, pages 511 - 515, XP002994515 *
THONGBOONKERD: "Alerations in the Renal Elatin-Elastase System in Type 1 Diabetic Nephropathy Identified by Proteomic Analysis", J.AM.SOC.NEPHROL, vol. 15, no. 3, March 2004 (2004-03-01), pages 650 - 662, XP002994513 *

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