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Dysregulation of interleukin 5 expression in familial eosinophilia
Author(s) -
Prakash Babu S.,
Chen Y.Y. K.,
BonneAnnee S.,
Yang J.,
Maric I.,
Myers T. G.,
Nutman T. B.,
Klion A. D.
Publication year - 2017
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13146
Subject(s) - eosinophilia , peripheral blood mononuclear cell , interleukin 5 , immunology , eosinophil , biology , gene expression , cytokine , microbiology and biotechnology , interleukin , gene , genetics , in vitro , asthma
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 m RNA expression was significantly increased in freshly isolated PBMC from affected family members, this was not accompanied by increased m RNA 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 m RNA expression was significantly increased in purified CD 3+ CD 4+, CD 14+, CD 19+, and ILC 2 cells from affected family members, as were IL ‐5 protein levels in supernatants from both stimulated PBMC and ILC 2 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).