Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1996-03-28
1999-05-04
Hutzell, Paula K.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
435 792, 435 793, 435 794, 435960, 435971, 435975, 436506, 436518, 436501, 436507, 436528, 436532, 436540, 436808, 436811, 436536, 5303891, 5303893, 530380, 530359, 5303871, G01N 3353
Patent
active
059003596
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a method for the immunological determination of oxidized lipoproteins utilizing the specific binding of oxidized lipoproteins to .beta.2-glycoprotein I (.beta.2-GPI), and to use thereof.
2. Description of Related Art
In general, lipids are sparingly soluble in water and hence are transported in vivo from one tissue to another in the form of lipoproteins, wherein triglycerides and cholesterol esters as non-polar lipids form a core which is covered with phospholipids and proteins. Depending on hydration density, lipoproteins are classified into four groups: chylomicron (up to 0.950 g/ml), very low density lipoprotein (VLDL, in the range of 0.950 to 1.006 g/ml), low density lipoprotein (LDL, in the range of 1.006 to 1.063 g/ml) and high density lipoprotein (HDL, in the range of 1.063 to 1.210 g/ml). The protein components in these lipoproteins are called "apolipoproteins".
Lipoproteins are deeply associated with the development and progress of arteriosclerosis as well as in vivo transport of lipids. One of the risk-factors for arteriosclerotic disease such as coronary arterioclerosis and cerebral arteriosclerosis is hyperholesterolemia wherein lipoproteins level (especially LDL level) in blood are increased. It is considered that in these diseases, LDL would take part in advancing arteriosclerosis, whereas HDL would have the opposite action to suppress arteriosclerosis.
Recent studies suggest that oxidized lipoproteins might accelerate the development of arteriosclerosis. That is, it is reported that at the initial stage of arteriosclerosis, an endothelial macrophage specifically phagocytoses an oxidized LDL abundant in cholesterol through a receptor to convert the oxidized LDL into foam cells. In contrast, a non-oxidized LDL is not phagocytosed by macrophage. This is also supported by the fact that oxidized LDL is observed in an immunological tissue staining utilizing antibodies to oxidized LDL to be widely distributed at the focal site of arteriosclerosis. It is also revealed that HDL possesses an activity of stimulating the release of cholesterol from foam cells, whereas this activity is seriously reduced in oxidized HDL.
As described above, it has been suggested that the development of arteriosclerotic diseases might be closely associated with oxidized lipoproteins. Accordingly, there is a possibility that assaying specifically for the oxidized lipoproteins could be of some assistance to analysis of the development mechanism of arteriosclerosis and to diagnosis for arteriosclerotic disease.
It is known that the oxidized lipoproteins are assayed by RIA or EIA using antibodies obtained by immunization of oxidized lipoproteins, as reported in Biochimica et Biophysica Acta, 963, 208-214 (1988), Proc. Natl. Acad. Sci. USA, 86, 1372-1376 (1989) and Clinica Chimica Acta, 218, 97-103 (1993).
SUMMARY OF THE INVENTION
The inventors have made detailed analysis on the form of oxidized lipoproteins present in blood. As a result, it has been found that .beta.2-GPI circulating in blood binds to oxidized lipoproteins at the oxidized site thereof. Further, it has been suggested that a complex of .beta.2-GPI and an oxidized lipoprotein would have an epitope similar to one present only in a complex of .beta.2-GPI and a phospholipids, because anti-cardiolipin antibodies derived from patients with anti-phospholipid antibody syndrome react with the complex of .beta.2-GPI and an oxidized lipoprotein. The present invention has thus been accomplished.
That is, the present invention relates to a method for determining the complex of .beta.2-GPI and an oxidized lipoprotein (.beta.2-GPI-oxidized lipoprotein complex) by a sandwich assay, using at least two reagents, a solid phase reagent selected from Group A below and an antibody reagent selected from Group B below (Method 1 of the present invention), and to a kit or use in the method (Kit 1 of the present invention): anti-apolipoprotein antibody
The present invention further relates to a meth
REFERENCES:
patent: 4877746 (1989-10-01), Jansson et al.
patent: 5472883 (1995-12-01), Matsuura et al.
Clark et al. 1987 Enzyme-Immunoassay, ed., by Edward T. Maggio CRC Press, Inc. Flonor, Chapter 8 pp. 167-178.
Hashimoto et al. (1992) J. Immunol. 149 (3), 1063-8.
McNally et al (1993) Nov. 15., vol. 72, 275-286.
Katahira Tomoyoshi
Koike Takao
Matsuura Eiji
Hutzell Paula K.
Masood Khalid
Yamasa Corporation
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