Diagnostic assay for source of inflammation

Abstract

A method of diagnosing the source of local, acute inflammation has been developed based on the discovery that white cells have different patterns of gene expression, and therefore protein markers, depending on the origin of the inflammation. These differences can be readily accessed by analysis of the white cells obtained at a site to be analyzed, for example, in the synovial fluid of a knee. The analysis, by comparison with the analysis of white cells present in known conditions, can be used to differentiate between inflammation due to bacterial infection, arthritis or gout, for example. The examples demonstrate differential gene expression in cells present in synovial fluid biopsies from patients with confirmed bacterial infection as compared to patients with aseptic loosening or patients with inflammation due to gout.

I claim: 
     
         1 . A method of diagnosing the type or origin of local inflammation comprising:
 determining the expression of one or more genes in a clinical sample obtained from a site of local inflammation and comparing the expression of these genes with their expression in known control samples.   
     
     
         2 . The method of  claim 1  wherein the gene expression is detected by examining nucleic acid expression. 
     
     
         3 . The method of  claim 1  wherein the gene expression is detected by examining protein expression. 
     
     
         4 . The method of  claim 1  wherein expression of a gene is determined by assaying for an mRNA transcribed from the gene or a protein translated from an mRNA transcribed from the gene. 
     
     
         5 . The method of  claim 1  wherein the sample is synovial or lymph fluid. 
     
     
         6 . The method of  claim 1  wherein the sample consists predominantly of neutrophils or other white cells. 
     
     
         7 . The method of  claim 1  wherein the sample is a fluid selected from the group consisting of blood, plasma, serum, urine, reproductive organ secretions, ascites fluid, peritoneal fluid, pleural fluid, pericardial fluid, cerebrospinal fluid, sputum, mucous secretions, and abscesses. 
     
     
         8 . The method of  claim 1  wherein the sample is cells from the fluid in  claim 6 . 
     
     
         9 . The method of  claim 1  wherein the sample is a tissue from biopsy, selected from a group consisting of bone, synovium, muscle, periprosthetic tissue, brain, nerve, skin, nasopharyngeal tissues, thyroid, tonsils, heart, lung, pancreas, gastrointestinal tissue, genitourinary tissue, liver, kidney, and gall bladder. 
     
     
         10 . The method of  claim 1  wherein the genes are analyzed on a microarray. 
     
     
         11 . The method of  claim 1  wherein the controls are obtained from individuals with confirmed infection. 
     
     
         12 . The method of  claim 1  wherein the controls are obtained from individuals with confirmed inflammation due to gout or autoimmune disease. 
     
     
         13 . The method of  claim 1  wherein the expression is compared by comparing protein expressed from the genes. 
     
     
         14 . The method of  claim 1  wherein the genes are selected from the group consisting of genes one through fifteen of Table I and genes one through sixteen of Table II. 
     
     
         15 . A method of screening for candidate therapeutic agents for treating inflammation, comprising the steps of
 administering a compound to be screened to an individual or site therein which is inflamed and then obtaining a sample from the site of inflammation; determining gene expression in the delis, and comparing the expression with the expression of genes in control cells.   
     
     
         16 . A kit for use in determining the expression of one or more genes in a clinical sample obtained from a site of local inflammation and comparing the expression of these genes with their expression in known control samples
 comprising means for analyzing the sample and   control expression patterns from normal white cells and white cells having known associations with specific diseases or disorders.   
     
     
         17 . The kit of  claim 16  further comprising reagents for analyzing genes. 
     
     
         18 . The kit of  claim 16  further comprising a software program for comparing expression patterns.