Evaluating and predicting clinical outcomes by gene expression analysis

Abstract

Methods of determining clinical outcomes in patients suffering from a pathological condition or syndrome are provided. Levels of intracellular gene expression re measured from a clinical sample provided by the patient, and the levels are compared to reference levels. Deviations from reference levels are predictive of clinical outcomes, for example, disease progression or response to therapeutic intervention.

What is claimed is:  
     
         1 . A method of evaluating a clinical outcome for a patient suffering from a clinical condition or syndrome, comprising the steps of 
 (a) providing a clinical specimen from said patient;    (b) measuring the levels of intracellular expression of a preselected set of genes in cells in said clinical specimen; and    (c) comparing said levels of expression against a set of reference expression levels, wherein a deviation of the level of expression of one or more of said preselected set of genes is indicative of clinical outcome for said patient.    
     
     
         2 . A method according to  claim 1 , wherein said clinical specimen is a sample of blood, tissue, or cerebrospinal fluid.  
     
     
         3 . A method according to  claim 2 , wherein said clinical specimen is a sample of blood.  
     
     
         4 . A method according to  claim 1 , wherein the expression levels of at least three genes are measured.  
     
     
         5 . A method according to  claim 1 , wherein the expression level of at least one proinflammatory cytokine is measured.  
     
     
         6 . A method according to  claim 4 , wherein the expression level of at least three proinflammatory cytokines is measured.  
     
     
         7 . A method according to  claim 6 , wherein said genes are selected from the group consisting of TNF-α, IL-6, IL-1, IL-8, IP-10 and MIP-1α.  
     
     
         8 . A method according to  claim 1 , wherein said clinical condition or syndrome is an inflammatory disorder.  
     
     
         9 . A method according to  claim 8 , wherein said inflammatory disorder is a chronic inflammatory disorder.  
     
     
         10 . A method according to  claim 9 , wherein said chronic inflammatory disorder is selected from the group consisting of chronic hepatitis, hepatitis B and C, chronic obstructive pulmonary disease, inflammatory mucosal disease, autoimmune disease, dementia, cardiovascular disease, and cancer.  
     
     
         11 . A method according to  claim 10 , wherein said inflammatory mucosal disease is selected from the group consisting of inflammatory bowel disease, Crohn's disease, and colitis.  
     
     
         12 . A method according to  claim 10 , wherein said dementia is AIDS-related dementia or Alzheimer's disease.  
     
     
         13 . A method according to  claim 10 , wherein said cancer is selected from the group consisting of lymphoma, prostate cancer, and colon cancer.  
     
     
         14 . A method according to  claim 1 , wherein said clinical outcome is response to a therapeutic intervention.  
     
     
         15 . A method according to  claim 14 , wherein said therapeutic intervention is treatment with a drug.  
     
     
         16 . A method according to  claim 15 , wherein said drug is a stabilized chlorite solution.  
     
     
         17 . A method according to  claim 16 , wherein said stabilized chlorite solution is WF-10.  
     
     
         18 . A method according to  claim 1 , wherein said clinical condition or syndrome is HIV infection.  
     
     
         19 . A method according to  claim 18 , wherein said clinical condition or syndrome is AIDS.  
     
     
         20 . A method according to  claim 1 , wherein said predicted clinical outcome is the probability of patient survival at a predetermined date.  
     
     
         21 . A method according to  claim 15 , wherein said predicted clinical outcome is the probability of patient survival after six months.  
     
     
         22 . A method according to  claim 1  wherein the levels of gene expression are measured by a quantitative polymerase chain reaction.  
     
     
         23 . A method according to  claim 22 , wherein the polymerase chain reaction is a reverse transcriptase/polymerase chain reaction.  
     
     
         24 . A method according to  claim 23 , wherein said polymerase chain reaction is carried out using fluorescent detection of the amplification products.  
     
     
         25 . A method according to  claim 1 , wherein said clinical condition is allograft rejection.