title: IL-5 receptor α levels in patients with marked eosinophilia or mastocytosis.
abstract: BACKGROUND
  IL-5 plays a central role in the development and maintenance of eosinophilia (EO) and eosinophil activation in a wide variety of eosinophilic disorders. Although IL-5, IL-3, and GM-CSF can modulate the expression of IL-5 receptor α (IL-5Rα) on eosinophils in vitro, little is known about soluble and surface IL-5Rα levels in vivo.
  
  
  OBJECTIVE
  To assess soluble and surface IL-5Rα levels in patients with EO and/or mastocytosis.
  
  
  METHODS
  Surface IL-5Rα expression was assessed by flow cytometry in blood and/or bone marrow from subjects with EO (n = 39) and systemic mastocytosis (n = 8) and from normal volunteers (n = 28). Soluble IL-5Rα (sIL-5Rα) level was measured in a cohort of 177 untreated subjects and correlated with EO, eosinophil activation, and serum tryptase and cytokine levels.
  
  
  RESULTS
  IL-5Rα expression on eosinophils inversely correlated with EO (r = -0.48; P < .0001), whereas serum levels of sIL-5Rα increased with the eosinophil count (r = 0.56; P < .0001) and serum IL-5 (r = 0.40; P < .0001) and IL-13 (r = 0.29; P = .004) levels. Of interest, sIL-5Rα level was significantly elevated in patients with systemic mastocytosis without EO. Although sIL-5Rα levels correlated with serum tryptase levels in these patients, eosinophil activation, assessed by CD69 expression on eosinophils and serum eosinophil-derived neurotoxin levels, was increased compared with that in normal subjects.
  
  
  CONCLUSIONS
  These data are consistent with an in vivo IL-5Rα regulatory pathway in human eosinophils similar to that described in vitro and involving a balance between soluble and surface receptor levels. This may have implications with respect to the use of novel therapeutic agents targeting IL-5 and its receptor in patients with EO and/or mastocytosis.
authors.affiliation: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Wilson
authors.forename: Irina
authors.initials: I
authors.lastname: Maric
authors.forename: Juhi
authors.initials: J
authors.lastname: Shukla
authors.forename: Margaret
authors.initials: M
authors.lastname: Brown
authors.forename: Carlo
authors.initials: C
authors.lastname: Santos
authors.forename: Olga
authors.initials: O
authors.lastname: Simakova
authors.forename: Paneez
authors.initials: P
authors.lastname: Khoury
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fay
authors.forename: Alexander
authors.initials: A
authors.lastname: Kozhich
authors.forename: Roland
authors.initials: R
authors.lastname: Kolbeck
authors.forename: Dean D
authors.initials: DD
authors.lastname: Metcalfe
authors.forename: Amy D
authors.initials: AD
authors.lastname: Klion
mesh_terms: D000328:Adult; D000368:Aged; D002469:Cell Separation; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D047208:Eosinophil-Derived Neurotoxin / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology / Q000378:metabolism*; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053666:Interleukin-5 Receptor alpha Subunit / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D034721:Mastocytosis, Systemic / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D053802:Tryptases / Q000097:blood; D055815:Young Adult
chemical_list: D016207:Cytokines; C485918:IL5RA protein, human; D053666:Interleukin-5 Receptor alpha Subunit; D047208:Eosinophil-Derived Neurotoxin; D053802:Tryptases