US2013344112A1PendingUtilityA1

Detection of an immune response

Assignee: BENAROYA RES INSTPriority: Feb 25, 2011Filed: Aug 23, 2013Published: Dec 26, 2013
Est. expiryFeb 25, 2031(~4.6 yrs left)· nominal 20-yr term from priority
G01N 2800/24G01N 2333/70596G01N 33/56977G01N 33/56972G01N 2333/726A61K 39/35G01N 33/6893G01N 2333/70514
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Claims

Abstract

Provided herein are methods of detecting and/or monitoring the presence or severity of an immune disorder in a subject, including detecting a frequency of a Th2a subset of CD4+ T cells in a biological sample of the subject. In some embodiments, the detecting includes: (a) detecting a frequency of CD4+ T cells in a biological sample of said subject; (b) detecting a frequency of a Th2a subset of the CD4+ T cells in the biological sample; and (c) comparing the frequency of the Th2a subset with the frequency of the CD4+ T cells.

Claims

exact text as granted — not AI-modified
1 . A method of detecting an immune disorder in a subject, comprising:
 (a) detecting a frequency of CD4+ T cells in a biological sample of said subject;   (b) detecting a frequency of a Th2a subset of the CD4+ T cells in the biological sample; and   (c) comparing the frequency of the Th2a subset with the frequency of the CD4+ T cells,   wherein a higher frequency of the Th2a subset as compared to a Th2a frequency in a control subject indicates said immune disorder.   
     
     
         2 . The method of  claim 1 , wherein the CD4+ T cells are total CD4+ T cells, total memory CD4+ T cells, or total CRTH2+ CD4+ T cells. 
     
     
         3 . The method of  claim 1 , wherein a frequency of:
 at least 50, at least 60, or at least 70 Th2a cells per 100,000 total CD4+ cells;   at least 75, at least 80, or at least 85 Th2a cells per 100,000 total memory CD4+ T cells; or   at least 3,000, at least 4,000 or at least 5,000 Th2a cells per 100,000 total CRTH2+ CD4+ T cells,   indicates that said subject has an immune disorder.   
     
     
         4 . The method of  claim 1 , wherein said immune disorder is an allergic disorder. 
     
     
         5 . The method of  claim 1 , wherein said immune disorder is an allergic disorder selected from: seasonal rhinoconjuctivitis, animal dander allergy, food allergy, and venom anaphylaxis. 
     
     
         6 . The method of  claim 1 , wherein said Th2a subset of the CD4+ T cells are CD161 positive, CD49d positive, CD27 negative and CD45RB negative. 
     
     
         7 . The method of  claim 1 , wherein said CD4+ Th2a cells are CD161 positive, CRTH2 positive, CD27 negative, CD49d positive and CD45RB negative. 
     
     
         8 . The method of  claim 1 , wherein said detecting step is carried out by fluorescent activated cell sorting (FACS). 
     
     
         9 . The method of  claim 1 , wherein said biological sample is a whole blood sample or a peripheral blood mononuclear cell (PBMC) sample. 
     
     
         10 . The method of  claim 9 , wherein said blood sample has a volume of from 0.05 to 10 milliliters. 
     
     
         11 . The method of  claim 9 , wherein said blood sample has a volume of from 0.1 to 5 milliliters. 
     
     
         12 . The method of  claim 1 , wherein said subject is a human subject. 
     
     
         13 . The method of  claim 12 , wherein said subject is between 0 and 5 years of age, and wherein said immune disorder is a food allergy. 
     
     
         14 . A method of monitoring immune deviation in a subject, comprising:
 (a) detecting a first frequency of CD4+ Th2a cells as compared to a frequency of CD4+ T cells in a first biological sample of said subject; and then   (b) detecting a second frequency of CD4+ Th2a cells as compared to a frequency of CD4+ T cells in a second biological sample of said subject,   wherein a lower number for the second frequency of said CD4+ Th2a in step (b) as compared to the first frequency in step (a) indicates immune deviation in said subject.   
     
     
         15 . The method of  claim 14 , wherein the CD4+ T cells are total CD4+ T cells, total memory CD4+ T cells, or total CRTH2+ CD4+ T cells, 
     
     
         16 . The method of  claim 14 , wherein the second biological sample is collected from about 2 weeks to about 1, 2, 3, 4 or 5 years after the first biological sample is collected from the subject. 
     
     
         17 . The method of  claim 14 , wherein said CD4+ Th2a cells are CD161 positive, CD49d positive, CD27 negative and CD45RB negative. 
     
     
         18 . The method of  claim 14 , wherein said CD4+ Th2a cells are CD161 positive, CRTH2 positive, CD27 negative, CD49d positive and CD45RBnegative. 
     
     
         19 . The method of  claim 14 , wherein one or both of said detecting steps is carried out by fluorescent activated cell sorting (FACS). 
     
     
         20 . The method of  claim 14 , wherein said biological sample is a whole blood sample or a peripheral blood mononuclear cell (PBMC) sample. 
     
     
         21 . The method of  claim 20 , wherein said blood sample has a volume of from 0.05 to 10 milliliters. 
     
     
         22 . The method of  claim 20 , wherein said blood sample has a volume of from 0.1 to 5 milliliters. 
     
     
         23 . The method of  claim 14 , wherein said monitoring is carried out during the course of an immunotherapy treatment. 
     
     
         24 . The method of  claim 23 , wherein said immunotherapy treatment is oral immunotherapy treatment (OIT), sublingual immunotherapy (SLIT), or subcutaneous immunotherapy (SCIT) treatment. 
     
     
         25 . The method of  claim 14 , wherein said subject is a human subject. 
     
     
         26 . The method of  claim 25 , wherein said subject is between 0 and 5 years of age, and said monitoring is carried out to monitor a food allergy in said subject. 
     
     
         27 - 30 . (canceled) 
     
     
         31 . A method of treating an immune disorder in a subject, comprising:
 detecting a Th2a cell frequency in said subject; and then, if the Th2a cell frequency is significant,   administering an immunotherapy treatment to said subject.   
     
     
         32 . The method of  claim 31 , wherein a frequency of:
 at least one Th2a cell per 3,000 total CD4+ cells;   at least one Th2a cell per 3,000 total memory CD4+ T cells; or   at least one Th2a cell per 50 total CRTH2+ CD4+ T cells, indicates that the Th2a cell frequency is significant.   
     
     
         33 . The method of  claim 31 , wherein a frequency of:
 at least one Th2a cell per 1,000 total CD4+ cells;   at least one Th2a cell per 500 total memory CD4+ T cells; or   at least one Th2a cell per 25 total CRTH2+ CD4+ T cells, indicates that the Th2a cell frequency is significant.   
     
     
         34 . The method of  claim 31 , wherein said immunotherapy treatment is oral immunotherapy treatment (OIT), sublingual immunotherapy (SLIT), or subcutaneous immunotherapy (SCIT) treatment.

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