Tuberculosis biomarkers and uses thereof

Abstract

The present invention provides biomarkers, methods and kits for diagnosing active tuberculosis in a subject, methods and kits for monitoring the effectiveness of treatment for active TB, as well as methods for identifying a compound that can treat TB reduce or inhibit the development of complications associated with the disease in a subject, and methods to treat active TB.

1 . A method for determining whether a subject has active tuberculosis (TB), the method comprising
 determining the level of one or more markers listed in Table 1 in a sample(s) from the subject;   comparing the level of the one or more markers in the subject sample(s) with a level of the one or more markers in a control sample(s), wherein a difference in the level of the one or more markers in the subject sample(s) as compared to the level of the one or more markers in the control sample(s) indicates that the subject has active TB.   
     
     
         2 . A method for monitoring the effectiveness of a treatment in a subject having active tuberculosis (TB), the method comprising
 determining the level of one or more markers listed in Table 1 in a first sample(s) from the subject prior to the initiation of the treatment;   determining the level of one or more markers listed in Table 1 in a second sample(s) from the subject after at least a portion of the treatment has been administered;   comparing the level of the one or more markers in the first sample(s) with a level of the one or more markers in the second sample(s), wherein a difference in the level of the one or more markers in the first sample(s) as compared to the level of the one or more markers in the second sample(s) indicates that the treatment is effective.   
     
     
         3 . The method of  claim 1  or  2 , wherein the level in the subject sample(s) is determined by mass spectrometry or immunoassay. 
     
     
         4 . The method of  claim 1  or  2 , wherein the sample(s) from the subject is a fluid sample(s) or a tissue sample(s). 
     
     
         5 . The method of  claim 1  or  2 , wherein the subject is HIV negative (HIV−) or HIV positive (HIV+). 
     
     
         6 . The method of  claim 1  or  2 , wherein the subject resides in North America or Europe. 
     
     
         7 . The method of  claim 1  or  2 , wherein the one or more markers is selected from the group consisting of APOE, SELL, TNXB, COMP, LUM, PGLYRP2, HABP2, LRG1, QSOX1, S100A8, APOC3, LCP1, VASN, PFN1, IGFBP6, LRG1, PGLYRP2, APOA4, BCHE, PI16, SEPP1, APOA1, IGFALS, CD14, TAGLN2, CPN2, APOC1, PEPD, GP1BA and PTGDS. 
     
     
         8 . The method of  claim 7 , further comprising determining the level of one or more markers selected from the group consisting of CPB2, GP1BA, GPS, GPX3, PROCR, VWF, ATRN, CD14, DBH, SELL, VCAM1, S100A8, S100A9, CD163, CPN1, FCN3, HIST2H2BE, KNG1, MASP1, MASP2, PROS1, YWHAZ, CAL ORM1, PDLIM1, PGLYRP2, LCAT, LPA, PCSK9, PON1, PTGDS, APOA1, APOA4, APOC1, APOC3, APOE, ANPEP, BCHE, BTD, CDHS, CLEC3B, CLU, CNTN1, ECM1, GPLD1, HABP2, HGFAC, HYOU1, IGFALS, IGFBP3, IGFBP6, LCP1, LGALS3BP, LUM, MINPP1, MST1, NCAM1, NID1, PEPD, PFN1, PRG4, QSOX1, SEPP1, SHBG, SPARC, TGFBI, THBS1, TLN1, TNXB, VASN, VTN, YWHAE, CA2, CKM, CNDP1, COMP, IGF2, LRG1, PI16, PRDX2, PTPRG, SPP2, TAGLN2, ZYX, MTB81, MTB51, CACNA2D1, CPN2, and MAN1A1. 
     
     
         9 . A kit for determining whether a subject has active tuberculosis (TB), the kit comprising reagents for determining the level of one or more markers listed in Table 1 in a subject sample(s) and instructions for use of the kit to determine whether the subject has active TB. 
     
     
         10 . A kit of monitoring the effectiveness of a treatment in a subject having active TB the kit comprising reagents for determining the level of one or more markers listed in Table 1 in a subject sample(s) and instructions for use of the kit to monitor the effectiveness of the treatment. 
     
     
         11 . The kit of any of  claim 9  or  10 , further comprising reagents for determining the level of one or more additional markers selected from the group consisting of APOE, SELL, TNXB, COMP, LUM, PGLYRP2, HABP2, LRG1, QSOX1, S100A8, APOC3, LCP1, VASN, PFN1, IGFBP6, LRG1, PGLYRP2, APOA4, BCHE, PI16, SEPP1, APOA1, IGFALS, CD14, TAGLN2, CPN2, APOC1, PEPD, GP1BA and PTGDS in a sample(s) from the subject. 
     
     
         12 .- 19 . (canceled)