Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1996-04-17
1999-08-10
Wolski, Susan
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
435 71, 435 721, 435 792, 436501, 436518, 436525, 436 63, 436 64, 436813, 5303879, 5303881, 53038885, 5303897, G01N 33574
Patent
active
059357983
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to the identification of a circulating protein associated with extracellular fiber matrix metabolism in mammalian connective tissues. More specifically, it is directed to assays for the detection and quantitation of molecules and fragments of YKL-40, a protein associated with connective tissue metabolism in mammals. It also involves correlating serum levels of YKL-40 in a mammal to the presence and status of diseases in which matrix metabolism plays a role, such as joint disorders and the metastasis of certain tumors.
2. Description of Related Art
The extracellular matrix of mammalian connective tissues (such as articular cartilage of joints and vascular wall tissue of the vascular and lymphatic system) provides strength to, and (to varying degrees) a barrier to the migration of cells from, the tissue. In certain disease processes, however, the matrix is degraded by hydrolytic enzymes. As the matrix degrades, the integrity of the tissue is impaired, which may allow tissue cells, by-products and other residues of the matrix metabolism to escape into bodily fluids and/or lymphatic or vascular circulation. Detection of these molecules and cells can, in certain instances, provide information regarding the biochemical characteristics of the extracellular matrix, including how it is synthesized and how it is lost. Also, where a particular molecule that is produced and/or secreted during abnormal matrix metabolism is closely related to a disease process, quantitation of that molecule in the patient's body fluids and/or tissues can help clinicians monitor the progress of the disease.
Human joint cartilage is known to contain several different types of proteins and proteoglycans, a few of which are present only in cartilage. These matrix constituents are released from cartilage tissue as it degrades during the course of certain joint diseases. The quantity of released matrix constituents (including fragments thereof and related macromolecules) present in a particular fluid or tissue may correlate with the intensity of the disease. Conversely, where the damage to the cartilage is reversible (as in secondary reactive arthritis caused by infection of the joint tissue), a reduction in levels of previously measured released matrix constituents may correlate with the degree of remission of the disease.
In practice, however, identification of reliable markers for metabolism of cartilage and other connective tissues and development of assays for their detection has proved to be a difficult task. Certain released fragments and molecules may be rapidly cleared from circulation by the lymph nodes, liver and phagocytosis (se, e.g., Frazer, et al., Hyaluronan: Sources, Turnover and Metabolism, Clinical Impact of Bone and Connective Tissue Markers 31-49 (Acad. Press, 1989); Smedsrod, "Catabolism in Liver Sinusoids", id. at 51-73; and, Heinegard, et al., Brit. J. Rheumatol., 30 (Suppl. 1): 21-24, 1991). Further, certain molecules are present in several different connective tissues, thus making correlation to metabolism in a particular tissue based on circulating levels of the molecule uncertain. Even where levels of a particular molecule can be traced to metabolism in the tissue of interest, the molecules may decline to undetectable levels or be biochemically altered in structure during those stages of a disease when a substantial quantity or connective tissue has been lost.
Not surprisingly, therefore, attempts to develop assays, especially those utilizing serum, which correlate levels of certain proteins to joint disease activity have met with mixed success. Rohde and co-workers have described radioimmunoassays (RIAs) for serum levels of amino-terminal type III procollagen peptide and its degradation products in rheumatoid arthritis (RA) patients (Rhode, et al. Eur. J. Clin. Invest, 9:451-459, 1979). This propeptide (P-III-NP) can be detected in several body fluids; a subsequent report attempted to correlate serum levels of P-III-NP to disease activity
REFERENCES:
patent: 4628027 (1986-12-01), Gay
patent: 5726061 (1998-03-01), Robbins et al.
patent: 5773259 (1998-06-01), Kirkpatrick et al.
Johansen et al., "A New Biochemical Marker for Joint Injury. Analysis of YKL-40 in Serum and Synovial Fluid," British Journal of Rheumatology, vol. 32, pp. 949-955 (1993).
Nyirkos et al., "Human synovial cells secrete a 39 kDa protein similar to a bovine mammary protein expressed during the non-lactating period," Biochemical Journal, vol. 268, pp. 265-268 (1990).
Hakala et al., "Human Cartilage gp-39, a Major Secretory Product of Articular Chondrocytes and Synovial Cells, Is a Mammalian Member of a Chitinase Protein Family," The Journal of Biological Chemistry, vol. 268, No. 34, pp. 25803-25810 (1993).
MacNaul et al., "Disooordinate Expression of Stromelysin, Collagenase, and Tissue Inhibitor of Metalloproteinases-1 in Rheumatoid Human Synovial Fibroblasts," The Journal of Biological Chemistry, vol. 265, No. 28, pp. 17238-17245 (1990).
Rejman et al., "Isolation and Characterization of a Novel 39 Kilodalton Whey Protein from Bovine Mammary Secretions Collected During the Nonlactating Period," Biochemical and Biophysical Research Communications, vol. 150, No. 1, pp. 329-334 (1988).
J. Johansen, et al. "Identification of Proteins Secreted by the Human Osteoblastic Cells in Culter", pp. 501-512 Journal of Bone and Mineral Research, vol. 7, No. 5, issued May 1992.
P. H. Maurer, et al., "Proteins and Polypeptides as Antigens", pp. 49-70, Methods in Enzymology, vol. 70, Issued 1980.
A. M. Campbell, "Monoclonal Antibody and Immunosensor Technology", pp. 1-114, Laboratory Techniques in Biochemistry and Molecular Biology, vol. 23, publ. 1982 (Elsevier).
K. J. Isselbacher, et al., "Harrison's Principles of Internal Medicine", pp. 1865-1867, 1870-1879, 1894-1896, publ.1980 (McGraw-Hill).
Johansen, et al., "Plasma YKL-40 Concentrations in Patients with Rheumatoid Arthritis", Abstract for Scientific Conference published on or after Jul. 12, 1992 in Davos, Switzerland.
Johansen Julia S.
Price Paul A.
The Regents of the University of California
Wolski Susan
LandOfFree
Assay for YKL-40 as a marker for degradation of mammalian connec does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Assay for YKL-40 as a marker for degradation of mammalian connec, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Assay for YKL-40 as a marker for degradation of mammalian connec will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1119200