title: Prostaglandin D2-supplemented "functional eicosanoid testing and typing" assay with peripheral blood leukocytes as a new tool in the diagnosis of systemic mast cell activation disease: an explorative diagnostic study.
abstract: BACKGROUND
  Systemic mast cell activation disease (MCAD) is characterized by an enhanced release of mast cell-derived mediators, including eicosanoids, which induce a broad spectrum of clinical symptoms. Accordingly, the diagnostic algorithm of MCAD presupposes the proof of increased mast cell mediator release, but only a few mediators are currently established as routine laboratory parameters. We thus initiated an explorative study to evaluate in vitro typing of individual eicosanoid pattern of peripheral blood leukocytes (PBLs) as a new diagnostic tool in MCAD.
  
  
  METHODS
  Using the "functional eicosanoid testing and typing" (FET) assay, we investigated the balance (i.e. the complex pattern of formation, release and mutual interaction) of prostaglandin E2 (PGE2) and peptido-leukotrienes (pLT) release from PBLs of 22 MCAD patients and 20 healthy individuals. FET algorithms thereby consider both basal and arachidonic acid (AA)-, acetylsalicylic acid (ASA)-, and substance P (SP)-triggered release of PGE2 and pLT. The FET assay was further supplemented by analyzing prostaglandin D2 (PGD2), as mast cell-specific eicosanoid.
  
  
  RESULTS
  We observed marked PGE2-pLT imbalances for PBLs of MCAD patients, as indicated by a markedly enhanced mean FET value of 1.75 ± 0.356 (range: 1.14-2.36), compared to 0.53 ± 0.119 (range: 0.36-0.75) for healthy individuals. In addition, mean PGD2 release from PBLs of MCAD patients was significantly, 6.6-fold higher than from PBLs of healthy individuals (946 ± 302.2 pg/ml versus 142 ± 47.8 pg/ml; P < 0.001). In contrast to healthy individuals, PGD2 release from PBLs of MCAD patients was markedly triggered by SP (mean: 1896 ± 389.7 pg/ml; P < 0.001), whereas AA and ASA caused individually varying effects on both PGD2 and pLT release.
  
  
  CONCLUSIONS
  The new in-vitro FET assay, supplemented with analysis of PGD2, demonstrated that the individual patterns of eicosanoid release from PBLs can unambiguously distinguish MCAD patients from healthy individuals. Notably, in our analyses, the FET value and both basal and triggered PGD2 levels were not significantly affected by MCAD-specific medication. Thus, this approach may serve as an in-vitro diagnostic tool to estimate mast cell activity and to support individualized therapeutic decision processes for patients suffering from MCAD.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schäfer
authors.forename: Peter
authors.initials: P
authors.lastname: Dreßen
authors.forename: Stefan
authors.initials: S
authors.lastname: Brettner
authors.forename: Norbert-Folke
authors.initials: NF
authors.lastname: Rath
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Molderings
authors.forename: Katrin
authors.initials: K
authors.lastname: Jensen
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany. christina.ziemann@item.fraunhofer.de.
authors.forename: Christina
authors.initials: C
authors.lastname: Ziemann
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001774:Blood Chemical Analysis / Q000379:methods; D016022:Case-Control Studies; D003955:Diagnostic Tests, Routine / Q000379:methods* / Q000639:trends; D015777:Eicosanoids / Q000032:analysis / Q000145:classification; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D015289:Leukotrienes / Q000097:blood; D008297:Male; D034721:Mastocytosis, Systemic / Q000097:blood / Q000175:diagnosis*; D008875:Middle Aged; D015230:Prostaglandin D2 / Q000097:blood* / Q000378:metabolism; D055815:Young Adult
chemical_list: D015777:Eicosanoids; D015289:Leukotrienes; D015230:Prostaglandin D2
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