Dysregulation of interleukin 5 expression in familial eosinophilia

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...

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Bibliographic Details
Published in:Allergy (Copenhagen) 2017-09, Vol.72 (9), p.1338-1345
Main Authors: Prakash Babu, S., Chen, Y.‐Y. K., Bonne‐Annee, S., Yang, J., Maric, I., Myers, T. G., Nutman, T. B., Klion, A. D.
Format: Article
Language:English
Subjects:
autosomal dominant
Blood diseases
CD14 antigen
CD19 antigen
CD3 antigen
CD4 antigen
Cell culture
Cells, Cultured
Chromosome 5
cytokine
Cytokines
DNA microarrays
eosinophil
Eosinophilia
Eosinophilia - metabolism
Gene Expression
Hereditary diseases
Humans
hypereosinophilic syndrome
Immunoassays
Immunoglobulin E
Interleukin 13
Interleukin 4
Interleukin 5
Interleukin-5 - biosynthesis
Interleukin-5 - blood
Interleukin-5 - genetics
Iron
Leukocytes (mononuclear)
Leukocytes, Mononuclear - metabolism
Lymphocyte Subsets - immunology
Lymphocyte Subsets - metabolism
Lymphocytes T
Peripheral blood mononuclear cells
Polymerase chain reaction
Real-Time Polymerase Chain Reaction
RNA, Messenger - blood
Serum levels
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Summary: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).
ISSN:0105-4538
1398-9995
1398-9995
DOI:10.1111/all.13146