Dysregulation of interleukin 5 expression in familial eosinophilia. Issue 9 (18th April 2017)

• Record Type: Journal Article
• Authors: Prakash Babu, S.; Chen, Y.‐Y. K.; Bonne‐Annee, S.; Yang, J.; Maric, I.; Myers, T. G.; Nutman, T. B.; Klion, A. D.
• Is Part Of: Allergy. Volume 72:Issue 9(2017:Sep.)
• Page Start: 1338
• Page End: 1345
• Publication Date: 2017-04-18
• Subjects: autosomal dominant -- cytokine -- eosinophil -- hypereosinophilic syndrome -- interleukin 5; Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.13146
• Languages: English
• ISSNs: 0105-4538

Abstract

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).