Submitted June 8, 2006
Accepted June 25, 2007
Demonstration of an aberrant mast cell population with clonal markers in a subset of patients with "idiopathic" anaphylaxis
Cem Akin*, Linda M. Scott, Can N. Kocabas, Nataliya Kushnir-Sukhov, Erica Brittain, Pierre Noel, and Dean D. Metcalfe
Division of Allergy and Immunology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, United States
Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, United States
Hematology Service, Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, MD, United States
* Corresponding author; email: cemakin{at}umich.edu.
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. Five of these 12 patients had evidence of one or more minor criteria for mastocytosis. C-kit mutational analysis was positive for the D816V 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 2003-2004 and was registered at http://clinicalcenter.nih.gov with a study number 03-I-0010. Since the study is now closed, it is no longer available online.
