Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1989-04-25
1993-03-02
Cererley, Mary E.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
G01N 33543
Patent
active
051908611
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a method of the diagnosis of rheumatoid arthritis by way of quantitation of collagenase inhibitor. More particularly the invention relates to a method for carrying out the diagnosis of rheumatoid arthritis, by means of a sandwich enzyme immunoassay for human collagenase inhibitor using monoclonal antibodies to bovine collagenase inhibitor (tissue inhibitors of metallproteinases: TIMP), on the basis of the fact that the amount of collagenase inhibitor in sera, plasmas or synovial fluids from patients with rheumatoid arthritis is clearly higher than the amount of collagenase inhibitor in sera, plasmas or synovial fluids, respectively, from normal subjects. The enzyme immunoassay mentioned above is used to mean a method for determining collagenase inhibitor which is characterized in that there are used two different monoclonal antibodies which specifically bind to different antigenic determinants of collagenase inhibitor as an antibody to be bound to a solid phase support and an antibody to be labeled with an enzyme.
BACKGROUND ART
Among heretofore used methods for the diagnosis of rheumatoid arthritis may be mentioned: Rose's method based on the detection of rheumatoid factor, modified Rose's method by Heller, RAHA-test and RA-test. These methods, however, have such disadvantages that they use complex experimental methods or that it takes many days to go through with the diagnosis.
Collagenase inhibitor has been known to exist in human's and other animals' bones, skins, dental pulps, amniotic fluids, bloods and synovial fluids as well as in cultures of joint chondrocytes, synovial cells, fibroblasts derived from varied tissues and fibrosarcomatous cells. As means for determining the amount of collagenase inhibitor methods have heretofore been known which are based on measurement of its biological activity. As described by Eisen et al. in J. Lab. Clin. Med. 75, 258-263 (1973) and also by Cawston et al. in Arthritis and Rheumatism 27, 285-290 (1984), however, it is impossible, with the heretofore known methods of determination, to assay sera, plasmas or synovial fluids for collagenase inhibitor activity since there exist in such fluids proteins, such as .alpha..sub.2 -macroglobulin, which interfere disturbingly with the measurement. Hayakawa, Iwata et al. have already developed a sandwich enzyme immunoassay (EIA) using monoclonal antibodies to bovine collagenase inhibitor, a method which enables specific quantitation of collagenase inhibitor with very small volumes of samples in a precise, straightforward and rapid manner (Japanese Patent Application No. Sho 62-42781). The present inventors have discovered that the level of collagenase inhibitor present in human sera, plasmas or synovial fluids apparently increases in association with affliction with rheumatoid arthritis, and found that it is possible to make a diagnosis of rheumatoid arthritis by determining, by the enzyme immunoassay mentioned above, the amount of collagenase inhibitor present in sera, plasmas or synovial fluids.
DISCLOSURE OF THE INVENTION
The present invention provides a method for diagnosing whether the subject is afflicted with rheumatoid arthritis, which comprises carrying out an enzyme immunoassay, with the aid of monoclonal antibodies that specifically bind to different antigenic determinants of bovine collagenase inhibitor as antibodies to be bound to a solid phase support and to be labeled with an enzyme, to measure the amount of human collagenase inhibitor present in the subject's sera, plasmas or synovial fluids, and comparing the measured amount with that for normal subjects.
In the above mentioned enzyme immunoassay employed according to the method of the present invention, a variety of materials in any usage forms which well adsorb passively antigens or antibodies may be chosen for use as solid supports, e.g. polystyrenes, polycarbonates, polypropylenes or polyvinyls in such forms as balls, microplates, sticks or test tubes. As the antibody to be labeled with an enz
REFERENCES:
Cawston et al., Arthritis and Rheumatism, vol. 27, No. 3, pp. 285-290 (1984).
Mercer et al., Biochem. J., 231(3), 505-510 (1985).
Borth et al., Clinica Chimica Acta, 117, pp. 219-225 (1981).
Eisen et al., J. Lab. Clin. Med. 75, 258-263 (1970).
Collagen Rel. Res., vol. 7, No. 5 (1987) pp. 341-350, Kodama et al.
The Journal of Biological Chemistry, vol. 258, No. 20, pp. 12259-12264 (1983), Welgus et al.
Hayakawa Taro
Iwata Hisashi
Iwata Kazushi
Kishi Junichi
Kodama Shuji
Cererley Mary E.
Fuji Yakuhin Kogyo Kabushiki Kaisha
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