Levels of bcma protein expression on b cells and use in diagnostic methods

Abstract

The present invention provides a method of measuring the levels of BCMA in a biological sample, specifically upon the B cell surface. The diagnostic assays are useful in predicting an individual's likelihood of developing or currently suffering from an autoimmune disease, such as SLE, and for methods for treating an individual clinically diagnosed with an autoimmune disease. This diagnostic test serves to predict a patient's likelihood to respond to a specific drug treatment, in particular treatment with BLyS antagonists, either singly or in combination with other immune suppressive drugs

1 . A method of detecting increased BCMA protein expression on the surface of B cells of an individual comprising:
 measuring a first level of BCMA protein expression in a biological sample and   comparing that level to a second level of BCMA protein expression present on the surface of B cells of a healthy individual and   determining the first level is increased as compared to the second level,   wherein said increased BCMA protein expression is associated with an autoimmune disease.   
     
     
         2 . The method of  claim 1 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener's disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud's syndrome, Sjorgen's syndrome and glomerulonephritis. 
     
     
         3 . The method of  claim 1  wherein said autoimmune disease is SLE. 
     
     
         4 . A method of treating an individual clinically diagnosed with an autoimmune disease, comprising:
 analyzing a biological sample from an individual clinically diagnosed with autoimmune disease for the presence or absence of elevated BCMA protein expression levels on their B cells, wherein the presence of elevated BCMA protein expression levels is associated with the clinical diagnosis of autoimmune disease; and   selecting a treatment plan that is most effective for individuals clinically diagnosed as having a condition associated with an increased BCMA protein expression level.   
     
     
         5 . The method of  claim 4  wherein said treatment plan involves administration of a BLyS antagonist. 
     
     
         6 . The method of  claim 5  wherein said BLyS antagonist is also an APRIL antagonist. 
     
     
         7 . The method of  claim 4 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener's disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud's syndrome, Sjorgen's syndrome and glomerulonephritis. 
     
     
         8 . The method of  claim 4  wherein said autoimmune disease is SLE. 
     
     
         9 . A method for predicting a patient's likelihood to respond to a drug treatment for an autoimmune disease, comprising determining the level of BCMA protein expression on the patient's B cells, wherein the presence of elevated BCMA protein expression levels is predictive of the patient's likelihood to respond to a drug treatment for the condition. 
     
     
         10 . The method of  claim 9  wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener's disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud's syndrome, Sjorgen's syndrome and glomerulonephritis. 
     
     
         11 . The method of  claim 9  wherein said autoimmune disease is SLE. 
     
     
         12 . The method of  claim 9  wherein said drug treatment involves administration of a BLyS antagonist. 
     
     
         13 . The method of  claim 12  wherein said BLyS antagonist is also an APRIL antagonist. 
     
     
         14 . An in vitro method of detecting increased BCMA protein expression on the surface of B cells of an individual, comprising:
 measuring the level of BCMA protein expression on the surface of B cells in a test biological sample from the individual;   comparing that level to the level of BCMA protein expression on the surface of B cells in a sample from a healthy control; and   determining whether the level of BCMA protein expression on the surface is B cells in the test biological sample is increased as compared to the level in the control sample;   
       wherein said increased BCMA protein expression is associated with an autoimmune disease. 
     
     
         15 . The method of  claim 14 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener's disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud's syndrome, Sjorgen's syndrome and glomerulonephritis. 
     
     
         16 . The method of  claim 14  wherein said autoimmune disease is SLE. 
     
     
         17 . An in vitro method of selecting a treatment plan that is most effective for treating an individual clinically diagnosed with an autoimmune disease, comprising: analyzing in vitro a biological sample from an individual clinically diagnosed with autoimmune disease for the presence or absence of elevated BCMA levels on their B cells, wherein the presence of elevated BCMA levels is associated with the clinical diagnosis of autoimmune disease. 
     
     
         18 . The method of  claim 17  wherein said treatment plan involves the use of a BLyS antagonist. 
     
     
         19 . The method of  claim 18  wherein said BLyS antagonist is also an APRIL antagonist. 
     
     
         20 . The method of  claim 17 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener's disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud's syndrome, Sjorgen's syndrome and glomerulonephritis. 
     
     
         21 . The method of  claim 17  wherein said autoimmune disease is SLE. 
     
     
         22 . An in vitro method for predicting a patient's likelihood to respond to a drug treatment for an autoimmune disease, comprising determining the level of BCMA expression on the surface of B cells in a sample from the patient; wherein the presence of elevated B cell levels is predictive of the patient's likelihood to respond to a drug treatment for the condition. 
     
     
         23 . The method of  claim 22  wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener's disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud's syndrome, Sjorgen's syndrome and glomerulonephritis. 
     
     
         24 . The method of  claim 22  wherein said autoimmune disease is SLE. 
     
     
         25 . The method of  claim 22  wherein said drug treatment comprises a BLyS antagonist. 
     
     
         26 . The method of  claim 25  wherein said BLyS antagonist is also an APRIL antagonist. 
     
     
         27 . A BLys antagonist for use in the treatment of an autoimmune disease in a patient, wherein said patient has elevated levels of BCMA expression on the surface of B cells. 
     
     
         28 . The antagonist of  claim 27  wherein the autoimmune disease is SLE. 
     
     
         29 . The antagonist of  claim 27  wherein said antagonist is a BLyS antibody. 
     
     
         30 . The antagonist of  claim 29  wherein said BLyS antibody is Lymphostat-B. 
     
     
         31 . The antagonist of  claim 29  wherein said antagonist is a receptor-extracellular domain/Fc domain fusion protein selected from the group consisting of TACI-Ig, BCMA-Ig, and BAFF-R-Ig. 
     
     
         32 . The antagonist of  claim 31  wherein said receptor-extracellular domain/Fc domain fusion protein is TACI-Ig. 
     
     
         33 . The antagonist of  claim 32  wherein said TACI-Ig is atacicept.