Biological Marker for Inflammation

Abstract

Inflammatory state in a subject is assayed by determining the level of expression of A 3 adenosine receptor (A 3 AR) in white blood cells (WBC), e.g. circulating WBCs, from the subject. A high level of expression of A 3 AR is indicative of an inflammatory state in the subject. This assay can be used for determining the severity of inflammation in a subject and monitoring the efficacy of anti-inflammatory treatment. Also, the level of expression may be used for selecting patients to receive an anti-inflammatory treatment that comprises an A 3 AR agonist.

1 . A method of determining an inflammatory state in a subject, comprising, determining the level of expression of A 3  adenosine receptor (A 3 AR) in white blood cells (WBC) from the subject, a high level of expression of A 3 AR being indicative of an inflammatory state in the subject. 
     
     
         2 . The method of  claim 1  wherein the level of said A 3 AR expression in the WBC is compared to a control level, the control level being the level of A 3 AR expression in normal WBC of a healthy subject, or being a standard reference level for the A 3 AR expression which is indicative of a normal state. 
     
     
         3 . The method according to  claim 1 , wherein the inflammatory state is the result of an autoimmune disease. 
     
     
         4 . The method according to  claim 3 , wherein the autoimmune disease is rheumatoid arthritis (RA). 
     
     
         5 . A method for determining the severity of an inflammatory state in a subject comprising determining the level of expression of A 3 AR in WBC of the subject and comparing the level of expression of A 3 AR in the cells with the level of prior determined standards that correlate A 3 AR expression level with severity of infection. 
     
     
         6 . The method according to  claim 5 , wherein the inflammatory state is the result of an autoimmune disease. 
     
     
         7 . The method according to  claim 6 , wherein the autoimmune disease is rheumatoid arthritis (RA). 
     
     
         8 . A method for determining the effectiveness of an anti-inflammatory therapeutic treatment of a subject, the treatment comprising administering an A 3 AR agonist to the subject, comprising determining the expression level of A 3 AR in white blood cells (WBCs) from the subject, in two or more successive time points, at least one of which is during an anti-inflammatory treatment, wherein a difference in the level being indicative of effectiveness of the drug treatment. 
     
     
         9 . The method of  claim 8  wherein one or more first samples are taken at a time point prior to initiation of the treatment and one or more second samples are taken at a time point during the treatment, wherein a decrease in the level of the A 3 AR expression in the one or more second samples as compared to the one or more first samples is indicative that the treatment is effective. 
     
     
         10 . The method of  claim 8  wherein one or more first samples are taken at a time point during the treatment and one or more second samples are taken at a time point during the treatment subsequent to the time point of the one or more first samples, wherein a decrease in the level of the A 3 AR expression in the one or more second samples as compared to the one or more first samples is indicative that the treatment is effective. 
     
     
         11 . The method of  claim 8  wherein one or more first samples are taken at a time point during the treatment and one or more second samples are taken at a time point after the treatment has been discontinued, wherein an increase in the level of the A 3 AR expression in the one or more second samples as compared to the one or more first samples is indicative that the treatment is effective. 
     
     
         12 . The method according to  claim 8  wherein said therapeutic treatment involves an anti-inflammatory drug. 
     
     
         13 . The method according to  claim 8 , wherein the inflammatory state is the result of an autoimmune disease. 
     
     
         14 . The method according to  claim 13 , wherein the autoimmune disease is rheumatoid arthritis (RA). 
     
     
         15 . A method for selecting a subject suffering from a certain inflammatory disease, to receive anti-inflammatory therapeutic treatment that comprises administering to the subject an A 3  adenosine receptor (A 3 AR) agonist, the method comprising determining the level of expression of A 3 AR in the while blood cells (WBCs) of the subject and selecting the subject to receive said anti-inflammatory therapeutic treatment if said level is above a predetermined level. 
     
     
         16 . The method of  claim 15 , wherein said sample of WBC is taken from a subject before receiving an anti-inflammatory treatment. 
     
     
         17 . The method according to  claim 15 , wherein the inflammatory state is the result of an autoimmune disease. 
     
     
         18 . The method according to  claim 18 , wherein the autoimmune disease is rheumatoid arthritis (RA). 
     
     
         19 . The method of  claim 15 , wherein said anti-inflammatory therapeutic treatment comprises providing said subject with an anti-inflammatory amount of IB-MECA. 
     
     
         20 . The method of  claim 15 , for selecting a candidate for receiving anti-inflammatory therapeutic treatment under clinical studies.