title: A novel immunodeficiency disorder characterized by genetic amplification of interleukin 25.
abstract: Many primary immunodeficiency disorders of differing etiologies have been well characterized, and much understanding of immunological processes has been gained by investigating the mechanisms of disease. Here, we have used a whole-genome approach, employing single-nucleotide polymorphism and gene expression microarrays, to provide insight into the molecular etiology of a novel immunodeficiency disorder. Using DNA copy number profiling, we define a hyperploid region on 14q11.2 in the immunodeficiency case associated with the interleukin (IL)-25 locus. This alteration was associated with significantly heightened expression of IL25 following T-cell activation. An associated dominant type 2 helper T cell bias in the immunodeficiency case provides a mechanistic explanation for recurrence of infections by pathogens met by Th1-driven responses. Furthermore, this highlights the capacity of IL25 to alter normal human immune responses.
authors.affiliation: Genomics Research Centre, Griffith Institute for Health and Medical Research, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: M R
authors.initials: MR
authors.lastname: Green
authors.forename: E
authors.initials: E
authors.lastname: Camilleri
authors.forename: M K
authors.initials: MK
authors.lastname: Gandhi
authors.forename: J
authors.initials: J
authors.lastname: Peake
authors.forename: L R
authors.initials: LR
authors.lastname: Griffiths
mesh_terms: D056915:DNA Copy Number Variations; D005784:Gene Amplification / Q000235:genetics*; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D020381:Interleukin-17