Use of hla genetic status to assess or select treatment of celiac disease

Abstract

Provided herein are methods of adjusting or selecting a gluten peptide therapy based on the human leukocyte antigen (HLA) genotype, in particular HLA-DQ2.5 homozygosity, of a subject having or suspected of having Celiac disease. Also provided herein are methods of identifying (e.g., diagnosing) a subject, such as a subject having or suspected of having Celiac disease and/or assessing the efficacy of treatment of Celiac disease, e.g. by determining responsiveness to a therapeutic gluten peptide composition or cytokine response, and kits relating thereto.

1 . A method, comprising: selecting or adjusting a gluten peptide treatment for a subject that has or is suspected of having Celiac disease based on a human leukocyte antigen (HLA) genotype of the subject. 
     
     
         2 . The method of  claim 1 , further comprising: assessing the HLA genotype of the subject. 
     
     
         3 . The method of  claim 2 , wherein assessing comprises determining the sequence of each copy of an HLA-DQA gene and each copy of an HLA-DQB gene in the subject. 
     
     
         4 . The method of  claim 3 , wherein determining comprises performing a nucleic-acid based assay on each copy of the HLA-DQA gene, or a portion thereof, and each copy of the HLA-DQB gene, or a portion thereof. 
     
     
         5 . The method of  claim 4 , wherein the nucleic-acid based assay is a probe-based assay or a sequencing assay. 
     
     
         6 . The method of  claim 1 , wherein assessing further comprises identifying the subject as having a homozygous HLA-DQ2.5 genotype or a non-homozygous HLA-DQ2.5 genotype. 
     
     
         7 . The method of  claim 6 , wherein the non-homozygous HLA-DQ2.5 genotype is a heterozygous HLA-DQ2.5 genotype. 
     
     
         8 . The method of  claim 7 , wherein the heterozygous HLA-DQ2.5 genotype is HLA-DQ 2.5/2.2 , HLA-DQ 2.5/7 , or HLA-DQ 2.5/8 . 
     
     
         9 . The method of  claim 1 , wherein the method further comprises:
 decreasing a dose of the gluten peptide treatment if the subject has a homozygous HLA-DQ2.5 genotype; or   maintaining or increasing the dose of the gluten peptide treatment if the subject has a non-homozygous HLA-DQ2.5 genotype.   
     
     
         10 . The method of  claim 1 , wherein the gluten peptide treatment comprises a composition comprising:
 a first peptide comprising the amino acid sequence PFPQPELPY (SEQ ID NO: 1) and the amino acid sequence PQPELPYPQ (SEQ ID NO:2);   a second peptide comprising the amino acid sequence PFPQPEQPF (SEQ ID NO:3) and the amino acid sequence PQPEQPFPW (SEQ ID NO:4); and   a third peptide comprising the amino acid sequence EQPIPEQPQ (SEQ ID NO:6) and the amino acid sequence PIPEQPQPY (SEQ ID NO:5).   
     
     
         11 . The method of  claim 10 , wherein:
 the first peptide comprises the amino acid sequence LQPFPQPELPYPQPQ (SEQ ID NO: 62);   the second peptide comprises the amino acid sequence QPFPQPEQPFPWQP (SEQ ID NO: 7); and   the third peptide comprises the amino acid sequence PEQPIPEQPQPYPQQ (SEQ ID NO: 8).   
     
     
         12 . The method of  claim 11 , wherein:
 the first peptide comprises the amino acid sequence ELQPFPQPELPYPQPQ (SEQ ID NO: 9), wherein the N-terminal glutamate is a pyroglutamate and the C-terminal glutamine is amidated;   the second peptide comprises the amino acid sequence EQPFPQPEQPFPWQP (SEQ ID NO: 10), wherein the N-terminal glutamate is a pyroglutamate and the C-terminal proline is amidated; and   the third peptide comprises the amino acid sequence EPEQPIPEQPQPYPQQ (SEQ ID NO: 11), wherein the N-terminal glutamate is a pyroglutamate and the C-terminal glutamine is amidated.   
     
     
         13 . The method of  claim 9 , wherein the dose is or is decreased to less than 300 micrograms if the subject has a homozygous HLA-DQ2.5 genotype. 
     
     
         14 . The method of  claim 13 , wherein the dose is or is decreased to less than 150 micrograms if the subject has a homozygous HLA-DQ2.5 genotype. 
     
     
         15 . A method, comprising:
 measuring a level of at least one circulating cytokine or chemokine in a subject that has or is suspected of having Celiac disease, wherein the subject has been administered a first composition comprising at least one gluten peptide in an amount selected based on a human leukocyte antigen (HLA) genotype of the subject, and   assessing the likelihood the subject has Celiac disease.   
     
     
         16 . The method of  claim 16 , further comprising:
 assessing the HLA genotype of the subject.   
     
     
         17 . The method of  claim 16 , wherein assessing comprises determining the sequence of each copy of an HLA-DQA gene and each copy of an HLA-DQB gene in the subject. 
     
     
         18 . The method of  claim 17 , wherein determining comprises performing a nucleic-acid based assay on each copy of the HLA-DQA gene, or a portion thereof, and each copy of the HLA-DQB gene, or a portion thereof. 
     
     
         19 - 46 . (canceled) 
     
     
         47 . A method for assessing tolerance to a gluten peptide in a subject having Celiac disease, the method comprising:
 measuring a level of at least one circulating cytokine or chemokine in a subject having Celiac disease, wherein the subject has been administered a first composition comprising at least one gluten peptide in an amount selected based on a human leukocyte antigen (HLA) genotype of the subject, and   assessing the tolerance of the subject to the at least one gluten peptide based on the measuring.   
     
     
         48 - 78 . (canceled) 
     
     
         79 . A method comprising:
 administering to a subject that has or is suspected of having Celiac disease a first composition comprising at least one gluten peptide in an amount selected based on an HLA genotype of the subject,   measuring a T cell response to a second composition comprising at least one gluten peptide in a sample from the subject, and   assessing the likelihood that the subject has Celiac disease.   
     
     
         80 - 87 . (canceled)