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J Allergy Clin Immunol. 2014 Apr;133(4):1195-202. doi: 10.1016/j.jaci.2013.06.037. Epub 2013 Aug 26.

Marked and persistent eosinophilia in the absence of clinical manifestations.

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  • 1Eosinophil Pathology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Frederick, Md.
  • 2Laboratory of Parasitic Diseases, Clinical Research Directorate/CMRP, SAIC-Frederick, Inc, Frederick National Laboratory for Cancer Research, Frederick, Md.
  • 3Department of Laboratory Medicine, Warren Magnusson Clinical Center, National Institutes of Health, Bethesda, Md.
  • 4Eosinophil Pathology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Frederick, Md. Electronic address:



Although most patients with hypereosinophilic syndromes (HES) present with clinical signs and symptoms attributable to eosinophilic tissue infiltration, some untreated patients remain asymptomatic or have signs and symptoms, such as allergic rhinitis, for which the relationship to peripheral eosinophilia is unclear (hypereosinophilia of unknown significance [HEUS]).


To identify and characterize subjects with HEUS of 5 years duration or more as compared to untreated patients with symptomatic HES and healthy normal volunteers.


All subjects with eosinophilia underwent yearly evaluation, including a standardized clinical evaluation, whole blood flow cytometry to assess lymphocyte subsets and eosinophil activation, and serum collection. Peripheral blood mononuclear cells were cultured overnight with and without phorbol 12-myristate 13-acetate/ionomycin. Cytokines and chemokines were measured in serum and cell supernatants, and mRNA expression was assessed by using quantitative real-time PCR.


Eight of the 210 subjects referred for the evaluation of eosinophilia (absolute eosinophil count [AEC] > 1500/μL) met the criteria for HEUS of 5 years duration or more (range, 7-29 years). Peak eosinophil count and surface expression of eosinophil activation markers were similar in subjects with HEUS and in untreated subjects with platelet-derived growth factor alpha-negative HES (n = 28). Aberrant or clonal T-cell populations were identified in 50% of the subjects with HEUS as compared to 29% of the subjects with HES (P = .12). Increased levels of IL-5, GM-CSF, IL-9, and IL-17A were also comparable in subjects with HEUS and HES. Serum levels of IgE and IL-13 were significantly increased only in subjects with HES.


A small number of patients with persistent peripheral eosinophilia (AEC > 1500/μL) appear to have clinically benign disease.


Eosinophil; cytokine; hypereosinophilic syndrome; pathogenesis

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