title: Dysregulation of interleukin 5 expression in familial eosinophilia.
abstract: BACKGROUND
  Familial eosinophilia (FE) is a rare autosomal dominant inherited disorder characterized by the presence of lifelong peripheral eosinophilia (>1500/μL). Mapped to chromosome 5q31-q33, the genetic cause of FE is unknown, and prior studies have failed to demonstrate a primary abnormality in the eosinophil lineage.
  
  
  OBJECTIVE
  The aim of this study was to identify the cells driving the eosinophilia in FE.
  
  
  METHODS
  Microarray analysis and real-time PCR were used to examine transcriptional differences in peripheral blood mononuclear cells (PBMC), and in purified cell subsets from affected and unaffected family members belonging to a single large kindred. Cytokine levels in serum and PBMC culture supernatants were assessed by suspension array multiplexed immunoassays.
  
  
  RESULTS
  Whereas IL-5 mRNA expression was significantly increased in freshly isolated PBMC from affected family members, this was not accompanied by increased mRNA expression of other Th2 cytokines (IL-4 or IL-13). Serum levels of IL-5 and IL-5 receptor α, but not IgE, were similarly increased in affected family members. Of note, IL-5 mRNA expression was significantly increased in purified CD3+ CD4+, CD14+, CD19+, and ILC2 cells from affected family members, as were IL-5 protein levels in supernatants from both stimulated PBMC and ILC2 cultures.
  
  
  CONCLUSIONS
  These data are consistent with the hypothesis that the eosinophilia in FE is secondary to dysregulation of IL-5 production in PBMC (and their component subsets).
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Prakash Babu
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Y-Y K
authors.initials: YK
authors.lastname: Chen
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Bonne-Annee
authors.affiliation: Laboratory of Human Retrovirology and Immunoinformatics, Applied and Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: I
authors.initials: I
authors.lastname: Maric
authors.affiliation: Genomic Technologies Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: T G
authors.initials: TG
authors.lastname: Myers
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: T B
authors.initials: TB
authors.lastname: Nutman
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: A D
authors.identifier: http://orcid.org/0000-0002-4986-5326
authors.initials: AD
authors.lastname: Klion
mesh_terms: D002478:Cells, Cultured; D004802:Eosinophilia / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D015848:Interleukin-5 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C508599:IL5 protein, human; D015848:Interleukin-5; D012333:RNA, Messenger
keywords: autosomal dominant; cytokine; eosinophil; hypereosinophilic syndrome; interleukin 5