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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 E 2  (PGE 2 ) 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 PGE 2  and pLT. The FET assay was further supplemented by analyzing prostaglandin D 2  (PGD 2 ), as mast cell-specific eicosanoid.    Results  We observed marked PGE 2 -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 PGD 2  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, PGD 2  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 PGD 2  and pLT release.    Conclusions  The new  in-vitro  FET assay, supplemented with analysis of PGD 2 , 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 PGD 2  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.    Electronic supplementary material  The online version of this article (doi:10.1186/s12967-014-0213-2) contains supplementary material, which is available to authorized users.

journal of translational medicine

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