Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with "idiopathic" anaphylaxis

Blood. 2007 Oct 1;110(7):2331-3. doi: 10.1182/blood-2006-06-028100. Epub 2007 Jul 16.


Idiopathic anaphylaxis remains a perplexing disorder in which existing prophylactic therapy is inadequate. In this prospective study, we sought to determine whether patients with idiopathic anaphylaxis might have evidence for a clonal disorder of mast cells related to mastocytosis and for which novel targeted therapies might be considered. We report 12 patients with "idiopathic" anaphylaxis who did not exhibit either urticaria pigmentosa or the characteristic bone marrow biopsy finding of multifocal mast-cell aggregates observed in systemic mastocytosis. Of these 12 patients, 5 had evidence of 1 or more minor criteria for mastocytosis. C-KIT mutational analysis was positive for the 816D>V activating mutation in 3 of 3 patients in CD25(+) bone marrow cells where the analysis was performed. These results demonstrate the presence of an aberrant mast-cell population carrying clonal markers in a subset of patients diagnosed with "idiopathic" anaphylaxis, who may respond to inhibitors targeting mutated C-KIT. This intramural clinical trial was conducted in 2003 and 2004 and was registered at ( with a study number 03-I-0010. Since the study is now closed, it is no longer available online.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Anaphylaxis / genetics
  • Anaphylaxis / metabolism*
  • Anaphylaxis / pathology*
  • Aspartic Acid / genetics
  • Biomarkers
  • Female
  • Humans
  • Leukocyte Count
  • Male
  • Mast Cells / cytology*
  • Mast Cells / metabolism*
  • Middle Aged
  • Mutation / genetics
  • Proto-Oncogene Proteins c-kit / genetics


  • Biomarkers
  • Aspartic Acid
  • Proto-Oncogene Proteins c-kit