Assay for Soluble CD200

Abstract

The disclosure relates to methods for identifying a subject having elevated CD200 levels and/or comprising cells overexpressing CD200, the method comprising the step of assaying a biological fluid from the subject to determine a level of soluble CD200, wherein a level above control indicates the subject has elevated CD200 levels. Diagnostic methods, methods of monitoring prognosis and methods of medical treatment relating to CD200 associated medical conditions are also provided. The disclosure also provides assays and kits useful in the diagnosis of a medical condition associated with elevated CD200 and/or comprising cells overexpressing CD200.

1 . A method for identifying a subject having an elevated CD200 level, the method comprising the step of assaying a biological fluid from the subject to determine a level of soluble CD200, wherein a level above control indicates the subject has elevated CD200 levels. 
     
     
         2 . The method according to  claim 1  for identifying a subject having cells that overexpress CD200, the method comprising the step of assaying a biological fluid from the subject to determine a level of soluble CD200, wherein a level above control indicates the presence of said cells. 
     
     
         3 . The method according to  claim 1  for identifying a subject having or at risk for a medical condition associated with elevated CD200, the method comprising the steps of:
 a) obtaining a sample of biological fluid from said subject; and 
 b) determining a level of soluble CD200 in said sample, 
 wherein a soluble CD200 level above control indicates the subject has or is at risk for said medical condition. 
 
     
     
         4 . The method according to  claim 1  for monitoring progression in a subject of a medical condition associated with elevated CD200, the method comprising the steps of:
 a) at a first time point, determining the level of soluble CD200 in a sample of biological fluid from the subject; and 
 b) comparing the level of soluble CD200 in a sample of biological fluid taken from said subject at a second time point different from said given time point; 
 wherein a difference in the soluble CD200 levels at the first time point compared to the second time point indicates modulated progression of the condition. 
 
     
     
         5 . A method of medical treatment useful to control progression of a medical condition associated with overexpression of CD200, comprising the steps of:
 a) identifying a subject having cells that overexpress cellular CD200 as determined by the method according to any of  claim 1 , and   b) treating the subject with an agent that inhibits signalling via the CD200:CD200R pathway.   
     
     
         6 . The method of medical treatment according to  claim 5  useful to control progression of a medical condition associated with elevated levels of CD200, comprising the steps of:
 a) identifying a subject having elevated levels of CD200 as determined by the assay method of the present disclosure, and 
 b) treating the subject with an agent that inhibits signalling via the CD200:CD200R pathway. 
 
     
     
         7 . The method according to  claim 3  for determining prognosis in a subject with cancer, optionally CLL, comprising the steps of: assaying a biological fluid from the subject to determine a level of soluble CD200 and comparing to a reference level, wherein a level above the reference level is indicative of poor prognosis. 
     
     
         8 . The method according to  claim 3  wherein the control is 0.4 ng/ml, 0.5 ng/ml, 0.6 ng/ml, 0.7 ng/ml, 0.8 ng/ml, 0.9 ng/ml, 1.0 ng/ml. 1.1 ng/ml, 1.2 ng/ml, 1.3 ng/ml, 1.4 ng/ml or 1.5 ng/ml. 
     
     
         9 . The method according to  claim 3  wherein the level of soluble CD200 detected in the subject tested is greater than 1.5 ng/ml, optionally greater than 1.6 ng/ml, optionally greater than 1.7 ng/ml, optionally greater than 1.8 ng/ml, optionally greater than 1.9 ng/ml and/or optionally greater than 2.0 ng/ml. 
     
     
         10 . The method according to  claim 7  wherein the reference level is 1.0 ng/ml. 
     
     
         11 . The method according to  claim 7  wherein reference level is about 1, 2, 3 standard deviations higher than the soluble CD200 level in CLL subjects with an average WBC count of 15.5, 20, 25, 30, 35, 40, 45 or 50. 
     
     
         12 . The method according to  claim 3 , wherein the biological fluid comprises blood and/or fractionated blood. 
     
     
         13 . The method according to  claim 3 , wherein the biological fluid comprises serum and/or plasma. 
     
     
         14 . (canceled) 
     
     
         15 . The method according to  claim 3 , wherein the biological fluid is substantially cell free. 
     
     
         16 . The method according to  claim 11 , wherein the biological fluid is neat serum. 
     
     
         17 . The method according to  claim 3 , wherein the medical condition is cancer. 
     
     
         18 . The method according to  claim 16  wherein the medical condition is a haematological malignancy, optionally CLL, AML, or MM. 
     
     
         19 .- 23 . (canceled) 
     
     
         24 . The method according to  claim 3  wherein the level of CD200 is determined with an antibody that binds to CD200. 
     
     
         25 . The method according to  claim 3 , wherein the subject is treated with an antibody that inhibits binding between CD200 and CD200R. 
     
     
         26 . The method according to  claim 25 , wherein the antibody is an antibody that binds and inhibits CD200. 
     
     
         27 . (canceled) 
     
     
         28 . The method of  claim 24 , wherein the antibody that binds CD200 is an antibody that binds the extracellular domain of CD200. 
     
     
         29 .- 38 . (canceled) 
     
     
         39 . An assay useful in the diagnosis of a medical condition comprising cells overexpressing CD200, comprising the steps of:
 a) obtaining a sample of biological fluid from a subject;   b) reacting the sample with an antibody that binds soluble CD200;   c) detecting bound soluble CD200; and   d) comparing the level of soluble CD200 in the sample with the level of soluble CD200 in a control subject, wherein a subject having said medical condition is indicated by a greater level of soluble CD200 in the sample relative to the level of soluble CD200 in a control subject.   
     
     
         40 . The assay of  claim 39  useful in the diagnosis of a medical condition associated with elevated levels of CD200, comprising the steps of:
 a) obtaining a sample of biological fluid from a subject; 
 b) reacting the sample with an agent that binds soluble CD200; 
 c) detecting bound soluble CD200; and 
 d) comparing the level of soluble CD200 in the sample with the level of soluble CD200 in a control, 
 
     
     
         41 .- 46 . (canceled) 
     
     
         47 . A kit comprising an antibody that binds soluble CD200 and instructions for the use thereof in determining the level of soluble CD200 in a sample. 
     
     
         48 .- 49 . (canceled)