Marker combinations for diagnosing infections and methods of use thereof

Abstract

A method of determining an infection type in a subject is disclosed. The method comprises measuring the concentration of a first determinant selected from the group consisting of the determinants which are set forth in Table 1 and a second determinant selected from the group of the determinants which are set forth in Table 2 in a subject derived sample, wherein the concentration is indicative of the infection type.

1 . A method of determining an infection type in a subject comprising measuring the concentration of a first determinant selected from the group consisting of the determinants which are set forth in Table 1 and a second determinant selected from the group of the determinants which are set forth in Table 2 in a sample derived from the subject, wherein said concentration is indicative of the infection type. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein said first determinant is NGAL, MMP8 or neopterin. 
     
     
         5 . The method of  claim 1 , wherein said first determinant is a polypeptide. 
     
     
         6 . A method of determining an infection type in a subject comprising measuring the concentration of at least two determinants which are set forth in Table 1 in a sample derived from the subject, wherein said concentration is indicative of the infection type. 
     
     
         7 - 8 . (canceled) 
     
     
         9 . The method of  claim 6 , wherein at least one of said at least two determinants is NGAL, MMP8 or neopterin. 
     
     
         10 - 16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein said second determinant is selected from the group consisting of TRAIL, CRP and IP-10. 
     
     
         18 . The method of  claim 17 , wherein said determinants comprise:
 (i) CRP and NGAL;   (ii) CRP and MMP8;   (iii) CRP and neopterin;   (iv) TRAIL and NGAL;   (v) TRAIL and MMP8;   (vi) TRAIL and neopterin;   (vii) IP10 and NGAL;   (viii) IP10 and MMP8; or   (ix) IP10 and neopterin; or   (x) Neopterin and PCT; or   (xi) NGAL and PCT.   
     
     
         19 . The method of  claim 6 , wherein said at least two determinants are:
 (i) NGAL and MMP8;   (ii) NGAL and neopterin; or   (iii) neopterin and MMP8.   
     
     
         20 . The method of  claim 1 , wherein said second determinant is TRAIL. 
     
     
         21 . The method of  claim 20 , wherein when the concentration of said TRAIL is higher than a pre-determined threshold value, a bacterial infection is ruled out for the subject. 
     
     
         22 . The method of  claim 20 , wherein when the concentration of said TRAIL is higher than a pre-determined threshold value, a viral infection is ruled in for the subject. 
     
     
         23 . The method of  claim 20 , further comprising measuring the concentration of CRP and/or IP-10. 
     
     
         24 . A method of determining an infection type in a child, comprising measuring the concentration of the determinant neopterin and/or the determinant NGAL in a sample derived from the child, wherein said concentration is indicative of the infection type. 
     
     
         25 . The method of  claim 24 , further comprising determining the concentration of at least one of the determinants set forth in Table 2. 
     
     
         26 . A method of determining an infection type in an adult, comprising measuring the concentration of the determinant osteopontin in a sample derived from the adult, and at least one of the determinants set forth in Table 2, wherein said concentration is indicative of the infection type. 
     
     
         27 . The method of  claim 1 , wherein no more than two determinants are measured. 
     
     
         28 . The method of  claim 1 , wherein no more than three determinants are measured. 
     
     
         29 . The method of  claim 1 , wherein no more than four determinants are measured. 
     
     
         30 . The method of  claim 1 , wherein the sample is whole blood or a fraction thereof. 
     
     
         31 . The method of  claim 30 , wherein said blood fraction sample comprises cells selected from the group consisting of lymphocytes, monocytes and granulocytes. 
     
     
         32 . The method of  claim 30 , wherein said blood fraction sample comprises serum or plasma. 
     
     
         33 . The method of  claim 1 , wherein the concentration of the determinant is determined electrophoretically or immunochemically. 
     
     
         34 . The method of  claim 33 , wherein the immunochemical detection is by flow cytometry, radioimmunoassay, immunofluorescence assay or by an enzyme-linked immunosorbent assay. 
     
     
         35 . The method of  claim 1 , wherein the concentration of the determinant is measured within about 24 hours after the sample is obtained. 
     
     
         36 . The method of  claim 20 , wherein the concentration of TRAIL is measured in a sample that was stored at 12° C. or lower, wherein said storage begins less than 24 hours after the sample is obtained. 
     
     
         37 . The method of  claim 1 , wherein said determinant of Table 1 is set forth in Table 5. 
     
     
         38 . The method of  claim 37 , wherein said determinant set forth in Table 5 is selected from the group consisting of NGAL, neopterin, and osteopontin. 
     
     
         39 . The method of  claim 37 , further comprising age normalization of the determinant concentration. 
     
     
         40 . The method of  claim 37 , further comprising stratifying the subject according to age and wherein the threshold is an appropriate age dependent threshold. 
     
     
         41 . A kit comprising a plurality of determinant detection reagents that specifically detect a first determinant selected from the group consisting of the determinants which are set forth in Table 1 and a second determinant selected from the group of the determinants which are set forth in Table 2. 
     
     
         42 . A kit comprising a plurality of detection reagents that specifically detect at least two determinants which are set forth in Table 1. 
     
     
         43 . (canceled) 
     
     
         44 . The kit of  claim 41 , wherein the detection reagent is an antibody or fragment thereof. 
     
     
         45 . The kit of  claim 41 , wherein said kit comprises antibodies that detect no more than 10 determinants.