title: Marked and persistent eosinophilia in the absence of clinical manifestations.
abstract: BACKGROUND
  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]).
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  A small number of patients with persistent peripheral eosinophilia (AEC > 1500/μL) appear to have clinically benign disease.
authors.affiliation: Eosinophil Pathology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Frederick, Md.
authors.forename: Yun-Yun K
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Eosinophil Pathology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Frederick, Md.
authors.forename: Paneez
authors.initials: P
authors.lastname: Khoury
authors.affiliation: Eosinophil Pathology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Frederick, Md.
authors.forename: JeanAnne M
authors.initials: JM
authors.lastname: Ware
authors.affiliation: Laboratory of Parasitic Diseases, Clinical Research Directorate/CMRP, SAIC-Frederick, Inc, Frederick National Laboratory for Cancer Research, Frederick, Md.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Holland-Thomas
authors.affiliation: Department of Laboratory Medicine, Warren Magnusson Clinical Center, National Institutes of Health, Bethesda, Md.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Stoddard
authors.affiliation: Department of Laboratory Medicine, Warren Magnusson Clinical Center, National Institutes of Health, Bethesda, Md.
authors.forename: Shakuntala
authors.initials: S
authors.lastname: Gurprasad
authors.affiliation: Eosinophil Pathology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Frederick, Md.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Waldner
authors.affiliation: Eosinophil Pathology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Frederick, Md. Electronic address: aklion@nih.gov.
authors.forename: Amy D
authors.initials: AD
authors.lastname: Klion
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054414:Chemokine CCL17 / Q000097:blood / Q000235:genetics; D002648:Child; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004802:Eosinophilia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D054414:Chemokine CCL17; D016207:Cytokines
keywords: Eosinophil; cytokine; hypereosinophilic syndrome; pathogenesis