title: Assessment of in vivo mast cell reactivity in patients with systemic mastocytosis.
abstract: BACKGROUND
  Patients with systemic mastocytosis (SM) have clinical signs of mast cell (MC) activation and increased levels of MC mediators. It is unclear whether the increased mediator levels are caused by increased numbers of tissue MCs, or whether these cells in affected individuals have a hyperactive phenotype.
  
  
  OBJECTIVE
  To determine reactivity of the skin and the airways to directly acting mediators and indirectly acting mast cell secretagogues in subjects with SM.
  
  
  METHODS
  Skin reactivity to morphine and histamine, and airway responsiveness to mannitol and methacholine, was assessed in 15 patients with SM, 11 patients with allergic asthma (A) and 13 healthy controls (HC). Serum tryptase and urinary metabolites of the MC mediators histamine and prostaglandin D2were measured, as well as ex vivo basophil histamine release.
  
  
  RESULTS
  Mast cell mediators in the blood and urine were significantly higher in patients with SM than in HC and A controls. Responsiveness to local activation of skin MCs (by morphine) and airway MCs (by mannitol) was similar in SM and HC groups. Likewise, end-organ responsiveness in the skin to histamine, and in the airways to methacholine, was similar in all three subject groups. There was no evidence of increased basophil reactivity in SM patients.
  
  
  CONCLUSIONS
  Mast cells in the skin and airways of subjects with SM do not exhibit hyper-reactivity towards the MC-activating stimuli morphine and mannitol, respectively. Therefore, the highly elevated baseline levels of MC mediators in SM are most likely due to increased MC numbers, rather than altered MC responsiveness. The underlying mechanisms could involve leakage of MC mediators, or dysfunctions in mediator synthesis, storage and release. One clinical implication of our study is that there is no contraindication to perform skin tests using morphine in subjects with mastocytosis.
authors.affiliation: Department of Medicine, Clinical Immunology and Allergy Research Unit, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.|Department of Respiratory Medicine and Allergy, Karolinska University Hospital Huddinge, Stockholm, Sweden.|Mastocytosis Centre Karolinska, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.|Centre for Allergy research (CfA), Karolinska Institutet, Stockholm, Sweden.
authors.forename: T
authors.identifier: http://orcid.org/0000-0002-1683-8882
authors.initials: T
authors.lastname: Gülen
authors.affiliation: Department of Medicine, Clinical Immunology and Allergy Research Unit, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Möller Westerberg
authors.affiliation: Department of Medicine, Clinical Immunology and Allergy Research Unit, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Lyberg
authors.affiliation: Department of Medicine, Clinical Immunology and Allergy Research Unit, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Ekoff
authors.affiliation: Department of Environmental Medicine, Experimental Asthma and Allergy Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Kolmert
authors.affiliation: Department of Environmental Medicine, Experimental Asthma and Allergy Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Bood
authors.affiliation: Department of Clinical R&D, Medivir AB, Huddinge, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Öhd
authors.affiliation: Centre for Allergy research (CfA), Karolinska Institutet, Stockholm, Sweden.|Department of Environmental Medicine, Experimental Asthma and Allergy Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: James
authors.affiliation: Centre for Allergy research (CfA), Karolinska Institutet, Stockholm, Sweden.|Department of Environmental Medicine, Experimental Asthma and Allergy Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: S-E
authors.initials: SE
authors.lastname: Dahlén
authors.affiliation: Department of Medicine, Clinical Immunology and Allergy Research Unit, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.|Mastocytosis Centre Karolinska, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.|Centre for Allergy research (CfA), Karolinska Institutet, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Nilsson
authors.affiliation: Mastocytosis Centre Karolinska, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.|Centre for Allergy research (CfA), Karolinska Institutet, Stockholm, Sweden.|Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Dahlén
mesh_terms: D000328:Adult; D000368:Aged; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D034721:Mastocytosis, Systemic / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D012129:Respiratory Function Tests; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D012882:Skin Tests; D055815:Young Adult
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D009569:Nitric Oxide; D007073:Immunoglobulin E; D006632:Histamine
keywords: histamine; mannitol; mast cell reactivity; mastocytosis; prostaglandin D2; tryptase