Identification of Unique Blood-Based Gene Expression Profiles in Children with Regressive Autism Spectrum Disorder (ASD) and Ileocolitis

Abstract

The invention provides compositions and methods for identifying autism and autism spectrum disorders in humans. The invention also includes compositions and methods for identifying unique blood-based gene expression profiles in children with regressive autism spectrum disorder (ASD) and ileocolitis.

1 . A method of treating a subject having a gastrointestinal disorder, the method comprising administering a treatment for gastrointestinal disorder to a pre-selected subject, wherein the subject is pre-selected by detecting an alteration in the level of a polypeptide or polynucleotide of at least one biomarker selected from the group consisting of FCER1A, CYP2S1, TMC4, IL1RN, TNFAIP3, CENPE, MTHFD2, and SIGLEC17P relative to a reference in a blood sample obtained from the subject. 
     
     
         2 . A method of diagnosing a gastrointestinal disorder in a subject, the method comprising measuring the level of a polypeptide or polynucleotide of at least one biomarker selected from the group consisting of FCER1A, CYP2S1, TMC4, IL1RN, TNFAIP3, CENPE, MTHFD2, and SIGLEC17P in a blood sample from the subject, wherein an alteration in the level of the polypeptide or polynucleotide relative to a reference indicates that the subject has a gastrointestinal disorder. 
     
     
         3 . The method of  claim 1 , wherein the subject is pre-selected by further detecting an alteration in the level of TNFRSF12A polypeptide or polynucleotide. 
     
     
         4 . The method of  claim 2 , further comprising measuring the level of TNFRSF12A polypeptide or polynucleotide. 
     
     
         5 . The method of  claim 1 , wherein the subject is pre-selected by detecting an alteration in the level of a IL1RN polypeptide or polynucleotide, MTHFD2 polypeptide or polynucleotide, and SIGLEC17P polypeptide or polynucleotide. 
     
     
         6 . The method of  claim 2 , wherein the method comprises measuring the level of a IL1RN polypeptide or polynucleotide, MTHFD2 polypeptide or polynucleotide, and SIGLEC17P polypeptide or polynucleotide. 
     
     
         7 . The method of  claim 1 , wherein the alteration comprises an increase in the level of TMC4 polypeptide or polynucleotide, an increase in the level of TNFAIP3 polypeptide or polynucleotide, a decrease in the level of FCER1A polypeptide or polynucleotide, a decrease in the level of CYP2S1 polypeptide or polynucleotide, a decrease in the level of TNFRSF12A polypeptide or polynucleotide, a decrease in the level of IL1RN polypeptide or polynucleotide, a decrease in the level of CENPE polypeptide or polynucleotide, a decrease in the level of MTHFD2 polypeptide or polynucleotide, or a decrease in the level of SIGLEC17P polypeptide or polynucleotide. 
     
     
         8 . The method of  claim 1 , wherein the gastrointestinal disorder is ileocolitis, ileitis, colitis, enteritis, duodenitis, gastritis, and/or esophagitis. 
     
     
         9 . The method of  claim 1 , wherein the subject is a child. 
     
     
         10 . The method of  claim 1 , wherein the subject has an autism spectrum disorder. 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 2 , further comprising a step of using the results obtained from the diagnostic assay to selecting or administering a treatment. 
     
     
         13 . The method of  claim 1 , wherein the treatment comprises corticosteroids, immunomodulators, 5-aminosalicylic acid preparations, cytokine specific antagonists, dietary restrictions, antimicrobials, probiotics, and/or supplemental digestive enzymes. 
     
     
         14 . A method of diagnosing autism spectrum disorder (ASD) in a subject, the method comprising measuring the level of a polypeptide or polynucleotide of at least one biomarker selected from the group consisting of FCER1A, CYP2S1, TMC4, IL1RN, TNFAIP3, CENPE, MTHFD2, and SIGLEC17P in a blood sample from the subject, wherein an alteration in the level of the polypeptide or polynucleotide relative to a reference indicates that the subject has autism spectrum disorder. 
     
     
         15 . The method of  claim 14 , further comprising measuring the level of TNFRSF12A polypeptide or polynucleotide. 
     
     
         16 . The method of  claim 14 , wherein the method comprises measuring the level of a polypeptide or polynucleotide of biomarkers IL1RN, MTHFD2, and SIGLEC17P. 
     
     
         17 . The method of  claim 14 , wherein the alteration comprises an increase in the level of TMC4 polypeptide or polynucleotide, an increase in the level of TNFAIP3 polypeptide or polynucleotide, a decrease in the level of FCER1A polypeptide or polynucleotide, a decrease in the level of CYP2S1 polypeptide or polynucleotide, a decrease in the level of TNFRSF12A polypeptide or polynucleotide, a decrease in the level of IL1RN polypeptide or polynucleotide, a decrease in the level of CENPE polypeptide or polynucleotide, a decrease in the level of MTHFD2 polypeptide or polynucleotide, or a decrease in the level of SIGLEC17P polypeptide or polynucleotide. 
     
     
         18 . The method of  claim 14 , wherein the autism spectrum disorder is autism. 
     
     
         19 . The method of  claim 14 , wherein said subject is a child. 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 14 , further comprising a step of using the results obtained from the diagnostic assay to selecting or administering a treatment. 
     
     
         22 . The method of  claim 21 , wherein the treatment comprises corticosteroids, immunomodulators, 5-aminosalicylic acid preparations, cytokine specific antagonists, dietary restrictions, antimicrobials, probiotics, and/or supplemental digestive enzymes. 
     
     
         23 - 25 . (canceled)