Methods of detecting and treating airway inflammatory diseases

Abstract

The present invention is related to novel methods for identifying and/or diagnosing and/or treating a population of subjects that are at risk for developing and/or have an inflammatory disease of the airways, including type 2 cytokine-driven airway inflammation.

1 . A method of identifying a subject having or at risk of having a type-2 (Th2) airway inflammatory disease, the method comprising:
 a. obtaining a blood sample from the subject;   b. determining the level of one or more interleukin-13 (IL-13) induced proteins in the sample; and   c. comparing the level of the one or more IL-13 induced proteins in the sample to a control sample wherein the presence and/or higher level of the one or more IL-13 induced proteins as compared to the control sample identifies the subject as having or at risk of having a type-2 airway inflammatory disease.   
     
     
         2 . The method of  claim 1 , wherein the type-2 airway inflammatory disease is Th2-high asthma. 
     
     
         3 . The method of  claim 1 , wherein the level of the one more IL-13 induced proteins is determined by a method selected from the group consisting of mass spectrometry, Western Blotting, Elisa and PCR. 
     
     
         4 . The method of  claim 1 , wherein the blood sample is a plasma sample. 
     
     
         5 . The method of  claim 1 , wherein the one or more IL-13 induced proteins is selected from the group consisting of IgG Fc-receptor binding protein (FCGBP), arachidonate 15-lipoxygenase (ALOX15), plasminogen activator inhibitor 2 (PAI2), carbonic anhydrase 2 (CA2), cystatin CN (CST1), periostin (POSTN), lysozyme C (LYZ), intelectin-1 (ITLN1), calcium-activated chloride channel 1 (CLCA 1), intelectin-2 (ITLN2), cystatin A (CSTA), mesothelin (MSLN), ST6 beta-galactosamide alpha-2,6-sialyltransferase 1 (SIAT1), mucin 5AC (MUC5AC), gelsolin (GSN), polymeric immunoglobulin receptor (PIGR), transcobalamin-1 (TCN1), lysyl oxidase homolog 4 (LOXL4), kallikrein-10 (KLK10), cadherin-6 (CDH6), secreted and transmembrane protein 1 (SECTM1), BPI fold-containing family B member 1 (BPIFB1), complement factor B (CFB), metalloproteinase inhibitor 1 (TIMP1), antileukoproteinase (SLP1), dipeptidyl peptidase 1 (CTSC), serpin B6 (SERPINB6), pigment epithelium-derived factor (SERPINF1), serpin B4 (SERPINB4), neutrophil gelatinase-associated lipocalin (LCN2), serpin B3 (SERPINB3) and combinations thereof. 
     
     
         6 . The method of  claim 1 , wherein the presence of one or more IL-13 induced proteins is selected from the group consisting of FCGBP, ALOX15, PAI2, POSTN, CST1, LYZ, ITLN1, CA2, ITLN2, CSTA, MSLN, MUC5A, TCN1, LOXL4, KLK10 and combinations thereof in the sample from the subject as compared to the control sample identifies the subject has having or at risk of having a Th2 airway inflammatory disease. 
     
     
         7 . The method of  claim 1 , wherein a higher level of one or more IL-13 induced proteins is selected from the group consisting of GSN, PIGR, CDH6, SCETM1, BPIFB1, CFB, TIMP1, SLP1, CTSC, SREPINB6, SERPINF1, SERPINB4, LCN2, SERPINB3 and combinations thereof as compared to the control sample identifies the subject has having or at risk of having a Th2 airway inflammatory disease. 
     
     
         8 . The method of  claim 1 , wherein the subject identified as having a type-2 (Th2) airway inflammatory disease is administered an inhaled corticosteroid. 
     
     
         9 . The method of  claim 1 , wherein the subject identified as having a Th2 airway inflammatory disease is administered a Th2 pathway inhibitor drug. 
     
     
         10 . A method of diagnosing and treating a type-2 (Th2) airway inflammatory disease, the method comprising:
 a. obtaining a blood sample from the subject;   b. determining the level of one or more IL-13 induced proteins in the sample;   c. comparing the level of the one or more IL-13 induced proteins in the sample to a control sample, wherein the presence and/or a higher level of the one or more IL-13 induced proteins as compared to the control sample identifies the subject as having a type-2 airway inflammatory disease; and   d. administering an effective amount of an inhaled corticosteroid and/or Th2 pathway inhibitor.   
     
     
         11 . The method of  claim 10 , wherein the type-2 airway inflammatory disease is Th2-high asthma. 
     
     
         12 . The method of  claim 10 , wherein the level of the one more IL-13 induced proteins is determined by a method selected from the group consisting of mass spectrometry, Western Blotting, Elisa and PCR. 
     
     
         13 . The method of  claim 10 , wherein the blood sample is a plasma sample. 
     
     
         14 . The method of  claim 10 , wherein the one or more IL-13 induced proteins is selected from the group consisting of FCGBP, ALOX15, PAI2, CA2, CST1, POSTN, lysozyme C LYZ), ITLN1, CLCA 1, ITLN2, CSTA, MSLN, SIAT1, MUC5AC, GSN, PIGR, TCN1, LOXL4, KLK10, CDH6, SECTM1, BPIFB1, CFB, TIMP1, SLP1, CTSC, SERPINB6, SERPINF1, SERPINB4, LCN2, SERPINB3 and combinations thereof. 
     
     
         15 . The method of  claim 10 , wherein the presence of one or more IL-13 induced proteins selected from the group consisting of FCGBP, ALOX15, PAI2, POSTN, CST1, LYZ, ITLN1, CA2, ITLN2, CSTA, MSLN, MUC5A, TCN1, LOXL4, KLK10 and combinations thereof in the sample from the subject as compared to the control sample identifies the subject has having or at risk of having a Th2 airway inflammatory disease. 
     
     
         16 . The method of  claim 10 , wherein a higher level of one or more IL-13 induced proteins selected from the group consisting of GSN, PIGR, CDH6, SCETM1, BPIFB1, CFB, TIMP1, SLP1, CTSC, SREPINB6, SERPINF1, SERPINB4, LCN2, SERPINB3 and combinations thereof as compared to the control sample identifies the subject has having or at risk of having a Th2 airway inflammatory disease. 
     
     
         17 . A method to endotype a subject as having Th2-high asthma, the method comprising:
 a. obtaining a blood sample from the subject;   b. determining the level of one or more IL-13 induced proteins in the sample; and   c. comparing the level of the one or more IL-13 induced proteins in the sample to a control sample wherein the presence and/or higher level of the one or more IL-13 induced proteins as compared to the control sample identifies the subject as having Th2-high asthma.   
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 17 , wherein the one or more IL-13 induced proteins is selected from the group consisting of FCGBP, ALOX15, PAI2, CA2, CST1, POSTN, lysozyme C LYZ), ITLN1, CLCA 1, ITLN2, CSTA, MSLN, SIAT1, MUC5AC, GSN, PIGR, TCN1, LOXL4, KLK10, CDH6, SECTM1, BPIFB1, CFB, TIMP1, SLP1, CTSC, SERPINB6, SERPINF1, SERPINB4, LCN2, SERPINB3 and combinations thereof. 
     
     
         20 . A method to predict the response of a subject to treatment with a Th2 pathway inhibitor, who has, or who is at risk of developing a Th2 airway inflammatory disease, the method comprising
 a. obtaining a blood sample from the subject;   b. determining the level of one or more interleukin-13 (IL-13) induced proteins in the sample;   c. comparing the level of the one or more IL-13 induced proteins in the sample to a control sample wherein the presence and/or higher level of the one or more IL-13 induced proteins as compared to the control sample identifies the subject as having or at risk of having a Th2 airway inflammatory disease responsive to treatment with a Th2 pathway inhibitor.   
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . A method to detect one or more IL-13 induced proteins and/or small molecules in a sample from a subject comprising:
 a. culturing airway epithelial cells obtained from the subject;   b. differentiating the cells at air-liquid interface (ALI);   c. treating cells with either bovine serum albumin (BSA) or IL-13 daily;   d. washing the treated cells; and   e. detecting IL-13 induced proteins and/or small molecules by mass spectrometry.   
     
     
         28 . (canceled) 
     
     
         29 . (canceled)