Biological markers for evaluating therapeutic treatment of inflammatory and autoimmune disorders

Abstract

Novel biological markers indicative of the action of an anti-inflammatory or immunosuppressive drug can be used to evaluate drug efficacy and compare local and systemic drug effects. They can also aid in comparison of different drugs, doses, and delivery routes. The biological markers include cell populations, cell surface antigen expression levels, and soluble factor concentrations. Measurement values of the novel biomarkers were shown to change significantly in allergic, atopic asthmatic, and healthy subjects after administration of prednisone.

1 . A method for determining whether a candidate drug is effective in treating a disease, comprising: 
 administering said candidate drug to a subject;    obtaining a biological sample from said subject;    measuring CD89 expression on granulocytes in said sample; and    comparing said measured expression with a standard expression.    
     
     
         2 . The method of  claim 1 , wherein said standard expression is obtained by measuring CD89 expression on granulocytes in an additional sample obtained from said subject before said candidate drug is administered.  
     
     
         3 . The method of  claim 1 , wherein a particular dose of said candidate drug is administered, and wherein the method further comprises determining whether said particular dose is effective in treating said disease in dependence on said comparison.  
     
     
         4 . The method of  claim 1 , wherein said candidate drug is administered by a particular delivery route, and wherein the method further comprises determining whether said particular delivery route is effective in treating said disease in dependence on said comparison.  
     
     
         5 . The method of  claim 1 , further comprising determining whether said candidate drug is effective in treating said disease in dependence on said comparison.  
     
     
         6 . The method of  claim 5 , wherein determining whether said candidate drug is effective comprises determining whether said measured expression is significantly higher than said standard expression.  
     
     
         7 . The method of  claim 1 , wherein said disease is selected from the group consisting of inflammatory diseases and autoimmune diseases.  
     
     
         8 . The method of  claim 7 , wherein said disease is asthma.  
     
     
         9 . The method of  claim 7 , wherein said inflammatory disease is atopy.  
     
     
         10 . The method of  claim 1 , wherein said biological sample is a blood sample.  
     
     
         11 . The method of  claim 1 , wherein measuring CD89 expression comprises measuring a percentage of said granulocytes that express CD89.  
     
     
         12 . The method of  claim 1 , wherein measuring CD89 expression comprises measuring intensity of CD89 expression per granulocyte.  
     
     
         13 . A method for determining whether a candidate drug is effective in treating a disease, comprising: 
 administering said candidate drug to a subject;    obtaining a biological sample from said subject;    measuring a quantity of MMP-3 in said sample; and    comparing said measured quantity with a standard quantity.    
     
     
         14 . The method of  claim 13 , wherein said standard quantity is obtained by measuring a quantity of MMP-3 in an additional sample obtained from said subject before said candidate drug is administered.  
     
     
         15 . The method of  claim 13 , wherein a particular dose of said candidate drug is administered, and wherein the method further comprises determining whether said particular dose is effective in treating said disease in dependence on said comparison.  
     
     
         16 . The method of  claim 13 , wherein said candidate drug is administered by a particular delivery route, and wherein the method further comprises determining whether said particular delivery route is effective in treating said disease in dependence on said comparison.  
     
     
         17 . The method of  claim 13 , further comprising determining whether said candidate drug is effective in treating said disease in dependence on said comparison.  
     
     
         18 . The method of  claim 17 , wherein determining whether said candidate drug is effective comprises determining whether said measured quantity is significantly higher than said standard quantity.  
     
     
         19 . The method of  claim 13 , wherein said disease is selected from the group consisting of inflammatory diseases and autoimmune diseases.  
     
     
         20 . The method of  claim 19 , wherein said disease is asthma.  
     
     
         21 . The method of  claim 19 , wherein said disease is atopy.  
     
     
         22 . The method of  claim 13 , wherein said biological sample is a blood sample.  
     
     
         23 . A method for determining whether a candidate drug is effective in treating a disease, comprising: 
 administering said candidate drug to a subject;    obtaining a biological sample from said subject;    measuring values of a set of factors in said sample, wherein said set of factors comprises at least two factors selected from the group consisting of: 
 CD89 expression on granulocytes,  
 CD38 expression on CD4 T cells,  
 HLA-DP, HLA-DQ, HLA-DR, and HLA-PAN expression on B cells,  
 CD62L expression on B cells,  
 monocyte count,  
 HLA-DP, HLA-DQ, HLA-DR, and HLA-PAN expression on monocytes,  
 MMP-3 concentration, and  
 SAA concentration; and  
   comparing said measured values with standard values.    
     
     
         24 . The method of  claim 23 , wherein said set of factors comprises at least three factors selected from said group.  
     
     
         25 . The method of  claim 23 , wherein said standard values are obtained by measuring values of said set of factors in an additional sample acquired from said subject before said candidate drug is administered.  
     
     
         26 . The method of  claim 23 , further comprising determining whether said candidate drug is effective in treating said disease in dependence on said comparison.  
     
     
         27 . The method of  claim 23 , wherein a particular dose of said candidate drug is administered, and wherein the method further comprises determining whether said particular dose is effective in treating said disease in dependence on said comparison.  
     
     
         28 . The method of  claim 23 , wherein said candidate drug is administered by a particular delivery route, and wherein the method further comprises determining whether said particular delivery route is effective in treating said disease in dependence on said comparison.  
     
     
         29 . The method of  claim 23 , wherein said disease is selected from the group consisting of inflammatory diseases and auto-immune diseases.  
     
     
         30 . The method of  claim 29 , wherein said disease is asthma.  
     
     
         31 . The method of  claim 29 , wherein said disease is atopy.  
     
     
         32 . The method of  claim 23 , wherein said biological sample is a blood sample.  
     
     
         33 . The method of  claim 23 , further comprising measuring values of at least one of granulocyte count and CRP concentration.  
     
     
         34 . A method for detecting a systemic effect of a drug in a subject, comprising: 
 obtaining a biological sample from said subject, wherein said sample is correlated with systemic activity;    measuring values of a set of factors in said sample, wherein said set comprises at least one factor selected from the group consisting of: 
 CD89 expression on granulocytes,  
 CD38 expression on CD4 T cells,  
 HLA-DP, HLA-DQ, HLA-DR, and HLA-PAN expression on B cells,  
 CD62L expression on B cells,  
 monocyte count,  
 HLA-DP, HLA-DQ, HLA-DR, and HLA-PAN expression on monocytes,  
 MMP-3 concentration, and  
 SAA concentration; and  
   comparing said measured values with standard values.    
     
     
         35 . The method of  claim 34 , wherein said drug is selected from the group consisting of anti-inflammatory drugs and immunosuppressive drugs.  
     
     
         36 . The method of  claim 35 , wherein said drug is a glucocorticoid.  
     
     
         37 . The method of  claim 36 , wherein said glucocorticoid is prednisone.  
     
     
         38 . The method of  claim 34 , wherein said biological sample is selected from the group consisting of blood and urine.  
     
     
         39 . The method of  claim 34 , further comprising obtaining a local biological sample from said subject, wherein said local biological sample is correlated with local activity, and measuring local values in said local biological sample.