title: The presence of mast cell clonality in patients with unexplained anaphylaxis.
abstract: BACKGROUND
  The mechanisms by which mast cells in patients with unexplained anaphylaxis (UEA) are triggered remain elusive. Onset of episodes is unpredictable and often recurrent. The substantial overlap between the clinical manifestations of UEA and clonal mast cell disorders (CMD) suggests an association between these rare disorders. The two forms of CMD characterized to date are systemic mastocytosis (SM) and monoclonal mast cell activation syndrome (MMAS).
  
  
  OBJECTIVE
  To examine the hypothesis that the pathogenesis of UEA reflects the presence of aberrant subpopulations of mast cells.
  
  
  METHODS
  Thirty (14 men, 16 women) patients (≥ 18 years) suffering from UEA and with no signs of cutaneous mastocytosis were recruited. Patients underwent an initial complete allergy work-up to confirm the diagnosis of UEA. Level of baseline serum tryptase (sBT) and total IgE were determined. In addition, a bone marrow examination was performed on all 30 patients to investigate possible underlying CMD.
  
  
  RESULTS
  Fourteen (47%) of our cases (nine men, five women) were diagnosed with CMD: 10 with SM and four with MMAS. Four of the 10 patients with SM had mast cell aggregates in their bone marrow. All patients with SM exhibited a sBT level > 11.4 ng/mL, whereas this level was elevated in only two of those with MMAS and four with UAE but not diagnosed with CMD. Total IgE levels were lower in the group of patients with CMD (P < 0.03).
  
  
  CONCLUSIONS
  The pathogenic mechanism underlying UEA could be explained by the presence of immunophenotypically aberrant mast cells with clonal markers in 47% of our subjects, indicating that clonal mast cell disorders are present in a substantial subset of these patients. Thus, the presence of CMD should be considered in patients with UEA if they have an elevated level of sBT (≥ 11.4 ng/mL) and cardiovascular symptoms such as syncope.
authors.affiliation: Department of Medicine Solna, Clinical Immunology and Allergy Research Unit, 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.initials: T
authors.lastname: Gülen
authors.forename: H
authors.initials: H
authors.lastname: Hägglund
authors.forename: B
authors.initials: B
authors.lastname: Sander
authors.forename: B
authors.initials: B
authors.lastname: Dahlén
authors.forename: G
authors.initials: G
authors.lastname: Nilsson
mesh_terms: D000328:Adult; D000368:Aged; D000707:Anaphylaxis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D001853:Bone Marrow / Q000473:pathology; D060965:Clonal Evolution; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006633:Histamine Antagonists / Q000627:therapeutic use; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D008415:Mastocytosis / Q000175:diagnosis / Q000209:etiology; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D053802:Tryptases / Q000097:blood
chemical_list: D006633:Histamine Antagonists; D007073:Immunoglobulin E; D053802:Tryptases
keywords: CD25; IgE; KIT D816V mutation; clonal mast cell disorders; idiopathic anaphylaxis; mast cell clonality; mastocytosis; tryptase; unexplained anaphylaxis