ABSTRACT
Mastocytosis is a rare myeloproliferative disease, characterised by accumulation of neoplastic mast cells in one or several organs. It presents as cutaneous or systemic. Patients with advanced systemic mastocytosis have a median survival of 3.5 years. The aetiology of mastocytosis is poorly understood, patients present with a broad spectrum of varying clinical symptoms that lack specificity to point clearly to a definitive diagnosis. Discovery of novel blood borne biomarkers would provide a tractable method for rapid identification of mastocytosis and its sub-types. Moving towards this goal, we carried out a clinical biomarker study on blood from twenty individuals (systemic mastocytosis: n = 12, controls: n = 8), which were subjected to global proteome investigation using the novel technology SWATH-MS. This identified several putative biomarkers for systemic mastocytosis. Orthogonal validation of these putative biomarkers was achieved using ELISAs. Utilising this workflow, we identified and validated CXCL7, LBP, TGFß1 and PDGF receptor-ß as novel biomarkers for systemic mastocytosis. We demonstrate that CXCL7 correlates with neutrophil count offering a new insight into the increased prevalence of anaphylaxis in mastocytosis patients. Additionally, demonstrating the utility of SWATH-MS for the discovery of novel biomarkers in the systemic mastocytosis diagnostic sphere.
Subject(s)
Anaphylaxis , Mastocytosis, Systemic , Mastocytosis , Acute-Phase Proteins , Anaphylaxis/etiology , Biomarkers , Carrier Proteins , Humans , Mast Cells , Mastocytosis, Systemic/complications , Mastocytosis, Systemic/diagnosis , Membrane Glycoproteins , Receptor, Platelet-Derived Growth Factor beta , Transforming Growth Factor beta1 , beta-ThromboglobulinABSTRACT
Exposure to overnutrition in utero may increase offspring cardiometabolic disease risk. A mouse model of maternal exposure to an obesogenic diet (DIO) was used to determine effects on fetal and placental weight and gene expression in mid- and late gestation. DIO altered placental gene expression in mid-gestation without differences in fetal or placental weights. Weight gain was attenuated in DIO dams in late gestation and male pup weight was reduced, however there were no persistent changes in placental gene expression. Differences in maternal weight gain and/or specific dietary components may impact on fetal and placental growth and later disease risk.
