Chemistry: analytical and immunological testing – Biospecific ligand binding assay
Patent
1996-08-02
1999-09-07
Wortman, Donna C.
Chemistry: analytical and immunological testing
Biospecific ligand binding assay
435 71, G01N 3353, G01N 33566
Patent
active
059486929
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to the technique to utilize effectively the amount and quality of the cartilage matrix components released into synovial fluid as an important source of information on the metabolism of the matrix. This invention relates to the biochemical diagnosis of joint diseases in the field of orthopedics. In the concrete, this invention relates to the method and measurement kit for assay of normal aggrecan and to the method of evaluation of informations on the joint.
In more detail, this invention relates to the method for assay of normal aggrecan that can detect only normal aggrecan present in the specimen, to the measurement kit used for the assay, and to the method of evaluation of informations on the joint which can judge whether the joint is pathological or normal and determine the type of the pathological joint, based on the absence or presence of significant difference between the amount of normal aggrecan and that of total proteoglycan in the specimen and those in synovial fluid obtained from a normal joint.
In this invention, "normal aggrecan" means aggrecan that is capable of binding hyaluronan.
BACKGROUND OF THE INVENTION
It is well known that in a normal joint cartilage, a good balance is maintained between synthesis and destruction of the cartilage matrix, while in a pathological joint cartilage, destruction of the cartilage matrix has been accelerated irrespective of the type of the lesion. Degradation products of the cartilage matrix are first released into synovial fluid, then distributed into blood, and metabolized. Thus the amount and quality of each component of the cartilage matrix released into synovial fluid is an important source of information on the metabolism of the matrix. Proteoglycan, the main component of the cartilage matrix, is characterized by its being capable of forming an aggregate with hyaluronan to build up the huge mass of matrix structure together with the type II collagen in the cartilage matrix. The amount and quality of aggrecan, the main proteoglycan in the cartilage matrix, and its sugar chain, glycosaminoglycan, is a clue to know whether the destruction of the cartilage matrix has been accelerated.
The conventional method for assay of normal aggrecan consists in measurement of the amount of the hyaluronan-aggrecan aggregate isolated by ultracentrifugation (Heinegard, D., et al., J. Biol. Chem.,249, 4250 (1974)) and gel chromatography (Iwata, H., Shin Seikagaku Jikken Koza, Vol.3, Carbohydrates II, p.452-455, Apr. 15, 1991, published by Tokyo Kagaku Dojin Kabushiki Kaisha). The method is time-consuming and requires not a small amount of specimen.
Therefore an improved method for assay of normal aggrecan is now required; namely a method that requires a shorter time and a smaller amount of specimen. Also a method has been desired that can clarify the quantitative relationship between the change in normal aggrecan and the pathological state of a joint to judge whether the joint is pathological or normal and identify the type of the pathological joint, as the basis of diagnosis of arthritis or decision of a therapeutical plan.
As described above, proteoglycan in synovial fluid is useful as a marker molecule for diagnosis of arthritis, though in some types of arthritis the concentration of proteoglycan is lower than that in the normal joint; thus the increased concentration of proteoglycan does not always indicate that the joint is pathological.
DISCLOSURE OF THE INVENTION
This invention intends to provide a method for assay of a novel marker molecule for differentiation of a pathological joint from a normal one. Moreover this invention intends to provide a method for assay of a marker molecule which can differentiate different types of arthritis with different characteristics.
More particularly this invention intends to provide a convenient and very sensitive method and a measurement kit for assay of normal aggrecan in a specimen, especially of body fluid, and to provide a method for evaluation of informations on the joint
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Horie Katuyuki
Miyauti Satoshi
Brumback Brenda G.
Seikagaku Corporation
Wortman Donna C.
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