CA2183589A1 - Method of assaying normal aggrecan, assaying kit, and method of judging joint-related information - Google Patents
Method of assaying normal aggrecan, assaying kit, and method of judging joint-related informationInfo
- Publication number
- CA2183589A1 CA2183589A1 CA002183589A CA2183589A CA2183589A1 CA 2183589 A1 CA2183589 A1 CA 2183589A1 CA 002183589 A CA002183589 A CA 002183589A CA 2183589 A CA2183589 A CA 2183589A CA 2183589 A1 CA2183589 A1 CA 2183589A1
- Authority
- CA
- Canada
- Prior art keywords
- normal
- normal aggrecan
- aggrecan
- joint
- proteoglycan
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 102000016284 Aggrecans Human genes 0.000 title claims abstract 70
- 108010067219 Aggrecans Proteins 0.000 title claims abstract 70
- 238000000034 method Methods 0.000 title claims abstract 38
- 102000016611 Proteoglycans Human genes 0.000 claims abstract 29
- 108010067787 Proteoglycans Proteins 0.000 claims abstract 29
- 238000003556 assay Methods 0.000 claims abstract 20
- 229920002674 hyaluronan Polymers 0.000 claims abstract 19
- KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 claims abstract 19
- 229940099552 hyaluronan Drugs 0.000 claims abstract 19
- 238000011156 evaluation Methods 0.000 claims abstract 12
- 230000027455 binding Effects 0.000 claims abstract 11
- 210000001179 synovial fluid Anatomy 0.000 claims abstract 11
- 238000001514 detection method Methods 0.000 claims abstract 9
- 238000005259 measurement Methods 0.000 claims abstract 9
- 230000001575 pathological effect Effects 0.000 claims abstract 4
- 201000005569 Gout Diseases 0.000 claims abstract 2
- 206010048873 Traumatic arthritis Diseases 0.000 claims abstract 2
- 201000010099 disease Diseases 0.000 claims abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 2
- 208000035474 group of disease Diseases 0.000 claims abstract 2
- 201000008482 osteoarthritis Diseases 0.000 claims abstract 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract 2
- 239000003153 chemical reaction reagent Substances 0.000 claims 9
- 238000000926 separation method Methods 0.000 claims 7
- 239000007790 solid phase Substances 0.000 claims 4
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims 3
- 101710132601 Capsid protein Proteins 0.000 claims 3
- 229920001287 Chondroitin sulfate Polymers 0.000 claims 3
- 229920000288 Keratan sulfate Polymers 0.000 claims 3
- 229940059329 chondroitin sulfate Drugs 0.000 claims 3
- KXCLCNHUUKTANI-RBIYJLQWSA-N keratan Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@H](COS(O)(=O)=O)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@H](O[C@@H](O[C@H]3[C@H]([C@@H](COS(O)(=O)=O)O[C@@H](O)[C@@H]3O)O)[C@H](NC(C)=O)[C@H]2O)COS(O)(=O)=O)O[C@H](COS(O)(=O)=O)[C@@H]1O KXCLCNHUUKTANI-RBIYJLQWSA-N 0.000 claims 3
- 238000011895 specific detection Methods 0.000 claims 3
- 206010003246 arthritis Diseases 0.000 claims 2
- 210000000845 cartilage Anatomy 0.000 claims 2
- 230000015556 catabolic process Effects 0.000 claims 2
- 230000006378 damage Effects 0.000 claims 2
- 238000006731 degradation reaction Methods 0.000 claims 2
- 239000012528 membrane Substances 0.000 claims 2
- 238000001914 filtration Methods 0.000 claims 1
- 238000001179 sorption measurement Methods 0.000 claims 1
- 230000009870 specific binding Effects 0.000 claims 1
- 208000012659 Joint disease Diseases 0.000 abstract 2
- 238000003745 diagnosis Methods 0.000 abstract 1
- 230000004069 differentiation Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 230000000399 orthopedic effect Effects 0.000 abstract 1
- 238000004393 prognosis Methods 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
Classifications
-
- 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
- G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
-
- 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
- G01N33/6887—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids from muscle, cartilage or connective tissue
-
- 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
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4722—Proteoglycans, e.g. aggreccan
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/10—Musculoskeletal or connective tissue disorders
- G01N2800/101—Diffuse connective tissue disease, e.g. Sjögren, Wegener's granulomatosis
- G01N2800/102—Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Rheumatology (AREA)
- Rehabilitation Therapy (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
A method for assay of normal aggrecan wherein normal aggre-can capable of binding hyaluronan is separated from proteoglycan incapable of binding hyaluronan so that only normal aggrecan can be detected, and a measurement kit used for the assay. Normal aggrecan thus separated is detected with a means for detection of proteoglycan. The specimen is preferably synovial fluid from the joint to be examined. A method for evaluation of information on a joint wherein information on the amount of normal aggrecan and the amount of total proteoglycan in the specimen is detected with said method and said measurement kit for assay of normal aggrecan, such information is compared with the previously obtained information on the amount of said substances in synovial fluid from a normal joint, and the information is evaluated to be the one derived from a normal joint or a pathological joint based on the absence or presence of significant difference. Presence of significant difference is considered to indicate a disease selected among a group of diseases consisting of osteoarthritis, rheumatoid arthritis, traumatic arthritis, and gout.
This invention is usable for biochemical diagnosis of joint diseases in the field of orthopedics. Determination of the concentration of normal aggrecan and the percentage of normal aggrecan in total proteoglycan is useful, for differentiation between a normal joint and a pathological joint, for understanding of the pathological conditions, such as the type of the joint disease and estimation of the prognosis, and also for evaluation of the effect of therapies.
This invention is usable for biochemical diagnosis of joint diseases in the field of orthopedics. Determination of the concentration of normal aggrecan and the percentage of normal aggrecan in total proteoglycan is useful, for differentiation between a normal joint and a pathological joint, for understanding of the pathological conditions, such as the type of the joint disease and estimation of the prognosis, and also for evaluation of the effect of therapies.
Claims (23)
1. A method for assay of normal aggrecan characterized in that only normal aggrecan in the specimen is detected after separation of normal aggrecan capable of binding hyaluronan from proteoglycan incapable of binding hyaluronan.
2. The method for assay of normal aggrecan of Claim 1 wherein separation of normal aggrecan capable of binding hyaluronan from proteoglycan incapable of binding hyaluronan comprises the following Processes A and B.
Process A: A process for degradation or removal of both hyaluronan bound to normal aggrecan and free hyaluronan in the specimen, Process B: A process for separation of normal aggrecan from proteoglycan other than normal aggrecan wherein the treated specimen in the Process A is brought into contact with a solid phase capable of binding or adsorbing normal aggrecan so that only normal aggrecan in the specimen may be bound to or adsorbed on the solid phase.
Process A: A process for degradation or removal of both hyaluronan bound to normal aggrecan and free hyaluronan in the specimen, Process B: A process for separation of normal aggrecan from proteoglycan other than normal aggrecan wherein the treated specimen in the Process A is brought into contact with a solid phase capable of binding or adsorbing normal aggrecan so that only normal aggrecan in the specimen may be bound to or adsorbed on the solid phase.
3. The method for assay of normal aggrecan of Claim 1, wherein the separation of normal aggrecan capable of binding hyaluronan from proteoglycan incapable of binding hyaluronan comprises the following Process A.
Process A: A process for separation of the aggregate of normal aggrecan bound to hyaluronan from proteoglycan incapable of binding hyaluronan in the specimen, based on the difference in molecular weight.
Process A: A process for separation of the aggregate of normal aggrecan bound to hyaluronan from proteoglycan incapable of binding hyaluronan in the specimen, based on the difference in molecular weight.
4. The method for assay of normal aggrecan of Claim 3, wherein said method for separation based on difference in molecular weight comprises a use of a filtering apparatus equipped with a membrane filter capable of collecting the aggregate of normal aggrecan bound to hyaluronan.
The method for assay of normal aggrecan of Claim 1, Claim 2, Claim 3, or Claim 4, wherein said method for detection of only normal aggrecan comprises a process for detection of separated normal aggrecan with a means for detection of proteoglycan.
6. The method for assay of normal aggrecan of Claim 5, wherein said means for detection of proteoglycan is a means for specific detection of keratan sulfate or chondroitin sulfate bound to proteoglycan or of the core protein of proteoglycan
7 The method for assay of normal aggrecan of Claim 1, Claim 2, Claim 3, Claim 4, Claim 5, or Claim 6, wherein the specimen is synovial fluid from the joint to be examined.
8. A measurement kit for assay of normal aggrecan, which is used in the method for assay of normal aggrecan of Claim 2, and comprises the following Reagents A, B, and C.
A: A reagent for degradation or removal of both hyaluronan bound to normal aggrecan and free hyaluronan in the specimen.
B: A solid phase for specific binding or adsorption of normal aggrecan, and C: A reagent for detection of normal aggrecan bound to or adsorbed on said solid phase described in above B.
A: A reagent for degradation or removal of both hyaluronan bound to normal aggrecan and free hyaluronan in the specimen.
B: A solid phase for specific binding or adsorption of normal aggrecan, and C: A reagent for detection of normal aggrecan bound to or adsorbed on said solid phase described in above B.
9. A measurement kit for assay of normal aggrecan of Claim 8, wherein said Reagent C is a reagent for specific detection of keratan sulfate or chondroitin sulfate bound to said normal aggrecan or of the core protein of normal aggrecan.
10. A measurement kit used in the method for assay of normal aggrecan of Claim 3, which is a measurement kit for assay of normal aggrecan comprising the following Apparatus A and Reagent B.
A: An apparatus for separation based on the difference in molecular weight, which can separate the aggregate of normal aggrecan bound to hyaluronan from proteoglycan incapable of binding hyaluronan in the specimen, and B: A reagent for detection of normal aggrecan which has been separated in the aggregate of normal aggrecan bound to hyaluronan.
A: An apparatus for separation based on the difference in molecular weight, which can separate the aggregate of normal aggrecan bound to hyaluronan from proteoglycan incapable of binding hyaluronan in the specimen, and B: A reagent for detection of normal aggrecan which has been separated in the aggregate of normal aggrecan bound to hyaluronan.
11. The measurement kit for assay of normal aggrecan of Claim 10, wherein said Apparatus A is a filter apparatus equipped with a membrane filter capable of collecting the aggregate of normal aggrecan bound to hyaluronan.
12 The measurement kit for assay of normal aggrecan of Claim 10 or Claim 11, wherein said Reagent B is a reagent for specific detection of keratan sulfate or chondroitin sulfate bound to said normal aggrecan or of the core protein of normal aggrecan.
13. The measurement kit for assay of normal aggrecan of Claim 8, Claim 9, Claim 10, Claim 11, or Claim 12, wherein the specimen is synovial fluid from the joint to be examined.
14. A method for evaluation of information on a joint, characterized in that information on the amount of normal aggre-can and the amount of total proteoglycan in the specimen is detected, and the information thus detected is evaluated to be the one derived from a patholoqical joint if a significant dif-ference is noted and is evaluated to be the one derived from a normal joint if a significant difference is not found, when the information is compared with the previously obtained information on the amount of normal aqgrecan and the amount of total proteo-glycan in synovial fluid from a normal joint.
The method for evaluation of information on a joint of Claim 14, wherein detection of information on the amount of normal aggrecan and the amount of total proteoglycan in the specimen consists in determination of the concentration of normal aggrecan in the specimen and also the concentration of total proteoglycan in the specimen with the method for assay of normal aggrecan of Claim 1, and calculation of the percentage of normal aggrecan in total proteoglycan
16 The method for evaluation of information on a joint of Claim 14 or Claim 15, wherein presence of said significant dif-ference means that the calculated percentage of normal aggrecan in total proteoglycan in the specimen is significantly lower than the previously determined percentage of normal aggrecan in total proteoglycan in synovial fluid from a normal joint
17. The method for evaluation of information on a joint of Claim 16, wherein a significantly lower percentage is considered to be an information derived from a pathological joint in a dis-ease selected among the group of diseases consisting of osteoar-thritis, rheumatoid arthritis, traumatic arthritis, and gout.
18. The method for evaluation of information on a joint of Claim 14, wherein detection of information on the amount of normal aggrecan in the specimen consists in determination of the concentration of normal aggrecan in the specimen with the method for assay of normal aggrecan of Claim 1, and the concentration of total proteoglycan in the specimen, and calculation of the concentration of proteoglycan other than normal aggrecan as the difference between the concentration of total proteoglycan and that of normal aggrecan.
19. The method for evaluation of information on a joint of Claim 14 or Claim 18, wherein presence of said significant dif-ference means that the concentration of normal aggrecan in the specimen is significantly lower than the previously determined concentration of normal aggrecan in synovial fluid from a normal joint and the concentration of proteoglycan other than normal aggrecan in the specimen is not significantly different from the previously determined concentration of proteoglycan other than normal aggrecan in synovial fluid from a normal joint.
20. The method for evaluation of information on a joint of Claim 19, wherein if there is a significant difference in the concentration of normal aggrecan, the information is considered to indicate a type of arthritis in which cartilage destruction makes a slow progress.
21. The method for evaluation of information on a joint of Claim 14 or Claim 18, wherein presence of said significant dif-ference means that the concentration of normal aggrecan in the specimen is not significantly different from the previously determined concentration of normal aggrecan in synovial fluid from a normal joint, and the concentration of proteoglycan other than normal aggrecan in the specimen is significantly higher than the previously determined concentration of proteoglycan other than normal aggrecan in synovial fluid from a normal joint.
22 The method for evaluation of information on a joint of Claim 21, wherein if there is a significant difference in the concentration of proteoglycan other than normal aggrecan, the information is considered to indicate a type of arthritis in which the cartilage destruction makes a rapid progress, and if there is no significant difference, the information is considered to indicate a normal joint
23. The method for evaluation of information on a joint of Claim 14, Claim 15, Claim 16, Claim 17, Claim 18, Claim 19, Claim 20, Claim 21, or Claim 22, wherein the specimen is synovial fluid from the joint to be examined.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5973994 | 1994-02-19 | ||
| JP6/59739 | 1994-02-19 | ||
| PCT/JP1995/000220 WO1995022765A1 (en) | 1994-02-19 | 1995-02-17 | Method of assaying normal aglycan, assaying kit, and method of judging joint-related information |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2183589A1 true CA2183589A1 (en) | 1995-08-24 |
| CA2183589C CA2183589C (en) | 2010-07-13 |
Family
ID=42352312
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2183589A Expired - Fee Related CA2183589C (en) | 1994-02-19 | 1995-02-17 | Method of assaying normal aggrecan, assaying kit, and method of judging joint-related information |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2183589C (en) |
-
1995
- 1995-02-17 CA CA2183589A patent/CA2183589C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2183589C (en) | 2010-07-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20140218 |