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

Journal of Translational Medicine

Christina Ziemann⁴  Katrin Jensen¹  Gerhard J Molderings⁵  Norbert-Folke Rath⁷  Stefan Brettner²  Peter Dreßen³  Dirk Schäfer⁶ 

[1] Institute of Medical Biometry and Informatics, University Heidelberg, Heidelberg, Germany;Department of Oncology, Haematology and Palliative Care, District Hospital of Waldbröl, Waldbröl, Germany;Department of Internal Medicine, St. Franziskus Hospital, Eitorf, Germany;Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany;Institute of Human Genetics, University Hospital of Bonn, Bonn, Germany;Medical Clinic III, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany;Oststadt-Heidehaus Hospital Laboratory, Klinikum Region Hannover (clinical centre of the Hannover region), Hannover, Germany

关键词: Arachidonic acid;    Acetylsalicylic acid;    Substance P;    Mastocytosis;    Functional eicosanoid testing and typing;    Peptido-leukotrienes;    PGD2;    PGE2;    Eicosanoids;    Systemic mast cell activation disease;   

Others  :  1148478
DOI  :  10.1186/s12967-014-0213-2

 received in 2014-03-17, accepted in 2014-07-21,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Schäfer et al.; licensee BioMed Central Ltd.

【 图 表 】

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