Chemistry: analytical and immunological testing – For preexisting immune complex or auto-immune disease
Reexamination Certificate
1998-12-03
2001-03-06
Nolan, Patrick (Department: 1644)
Chemistry: analytical and immunological testing
For preexisting immune complex or auto-immune disease
C435S007200, C530S388700, C530S389600, C530S395000
Reexamination Certificate
active
06197596
ABSTRACT:
BACKGROUND OF THE INVENTION
(a) Field of the Invention
The invention relates to the monitoring and/or prognostic of antibody-mediated autoimmune diseases, and treatments thereof.
(b) Description of Prior Art
Systemic lupus erythematosus (SLE) is a disease that predominantly affects women, and is characterized by high levels of circulating autoantibodies, which are thought to play an integral role in its pathogenesis. Most of the autoantibodies are specific for proteins that are normally sequestered inside the cell. Much recent interest has focused on the role that apoptosis plays in the movement of these autoantigens to blebs at the cell surface. We speculate that if this happened every time apoptosis occurred, inflammation would occur throughout the body in individuals with high levels of these circulating autoantibodies. This, however, does not occur in SLE, where the disease is more tissue specific with skin lesions and arthritis the most common features. Less common, but generally associated with morbidity, are the renal complications. We reasoned that there must be another level of control, which leads to the inflammation at the different sites. One protein of interest is clusterin, which is induced by the same stimuli that induce apoptosis, such as TNF, UVB irradiation, and serum deprivation.
Clusterin (also known as apoJ, and complement lysis inhibitor) is a 70-80 kD heterodimeric sulfated glycoprotein that is expressed by a large number of cells, including epithelial, polymorphonuclear and neuronal cells, as well as platelets. It has a protective role, and its expression at sites of tissue remodeling and apoptosis is thought to prevent antibody mediated lysis and inflammation. Clusterin not only binds and inhibits the terminal components of complement, but also binds immunoglobulin, apo-IA, and TGF receptors (both type I and II).
It would be highly desirable to be provided with means to monitor antibody-mediated autoimmune diseases.
SUMMARY OF THE INVENTION
One aim of the present invention is to provide means to monitor antibody-mediated autoimmune diseases.
Another aim of the present invention is to provide treatments of antibody-mediated autoimmune diseases.
In accordance with the present invention there is provided a method to determine antibody-mediated autoimmune diseases in a patient, which comprises the steps of:
a) determining the amount of clusterin present in a serum, saliva or tissue sample of the patient with an anti-clusterin antibody;
b) comparing the amount of clusterin in step a) with normal serum, saliva or tissue sample, wherein a lower than normal amount is indicative of antibody-mediated autoimmune and/or injury-mediated disease.
In accordance with the present invention there is provided a method to monitor antibody-mediated autoimmune diseases in a patient, which comprises measuring the clusterin levels according to the method of the present invention weekly to monthly to follow disease activity, wherein a drop in the clusterin levels is indicative of more active disease which necessitates more aggressive treatment.
In accordance with the present invention there is provided a method for the treatment of antibody-mediated autoimmune diseases in a patient, which comprises administering a pharmaceutically effective amount of an agent which increases clusterin expression.
The agent includes, without limitation, folic acid, tamoxifen and Tripterigium Wilfordii Hook(TWH-f).
For the purpose of the present invention the following terms are defined below.
The expression “antibody-mediated autoimmune diseases” is intended to mean any diseases caused by or related to antibodies present in a patient, including, without limitation, diseases such as dermatomyositis, thyroiditis, systemic lupus erythematosus, Sjogren's syndrome, IgA nephropathy, and others, as well as other injury related diseases where antibodies play a role.
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Hogasen, K. et al.,J. Immunol. Meth.160:107-115 (1993).
Liang, M.H. et al.,Arthritis Rheum.32:1107-1118 (1989).
The Merck Manual. 16thEdition, 1992, pp. 338-342.
Rosenberg et al. Int. J. Biochem. Cell. Biol. vol. 27: 633-645, 1995.
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Witte et al.; Am. J. of Pathol.; vol. 143; No. 3; p. 763-773, 1993.
Murakami et al.; J. of Biol. Chem. vol. 266; p. 15414-15419, 1991.
McGill University
Nixon & Peabody LLP
Nolan Patrick
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