Patients with idiopathic anaphylaxis (IA) continue to be admitted for study. The majority of the patients are admitted to the inpatient unit and undergo a history and physical examination, a blood draw for routine studies, and a bone marrow biopsy and aspirate in an attempt to elucidate the etiology and evaluate the pathogenesis of their disease. In collaboration with the NIH Clinical Center's myeloid core facility, we assess all the patient bone marrow aspirates and biopsies obtained based on the current WHO criteria to diagnose systemic mastocytosis. We are also engaged in exploring mechanisms of anaphylaxis in NSAID dependent and independent food-induced anaphylaxis. In a now completed study, we used transcriptome analysis to define patients with lipid-transfer protein-induced anaphylaxis to profile possible disturbances in gut epithelium homestasis, which may be a factor in allergic sensitization. This study highlights gene networks that may be important in IgG-induced anaphylaxis. We are evaluating alternate pathways in anaphylaxis that may be an etiology of non-IgE-mediated anaphylaxis in patients with idiopathic anaphylaxis. A study on adverse reactions to an erythropoietin peptide mimetic illustrates the importance of atypical activation of the anaphylaxis pathway. The randomized treatment protocol with omalizumab (09-I-0129) is in the patient accrual stage. Omalizumab is approved for the treatment of severe asthma and acts through a mechanism that down regulates the IgE receptor on the surface of basophils, mast cells, and dendritic cells. Omalizumab has been reported to be useful as adjunct therapy in the treatment of diseases other than asthma such as food allergy and chronic urticaria. There have been no serious adverse events to date in the study drug, in particular drug-induced anaphylaxis.

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8
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2016
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Metcalfe, Dean D; Mekori, Yoseph A (2017) Pathogenesis and Pathology of Mastocytosis. Annu Rev Pathol 12:487-514
Carter, Melody C; Desai, Avanti; Komarow, Hirsh D et al. (2017) A distinct biomolecular profile identifies monoclonal mast cell disorders in patients with idiopathic anaphylaxis. J Allergy Clin Immunol :
Lyons, Jonathan J; Yu, Xiaomin; Hughes, Jason D et al. (2016) Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number. Nat Genet 48:1564-1569
Muñoz-Cano, Rosa; Pascal, Mariona; Bartra, Joan et al. (2016) Distinct transcriptome profiles differentiate nonsteroidal anti-inflammatory drug-dependent from nonsteroidal anti-inflammatory drug-independent food-induced anaphylaxis. J Allergy Clin Immunol 137:137-146
Boyden, Steven E; Metcalfe, Dean D; Komarow, Hirsh D (2016) Vibratory Urticaria and ADGRE2. N Engl J Med 375:95
Kotarek, Joseph; Stuart, Christine; De Paoli, Silvia H et al. (2016) Subvisible Particle Content, Formulation, and Dose of an Erythropoietin Peptide Mimetic Product Are Associated With Severe Adverse Postmarketing Events. J Pharm Sci 105:1023-7
Kirshenbaum, Arnold S; Cruse, Glenn; Desai, Avanti et al. (2016) Immunophenotypic and Ultrastructural Analysis of Mast Cells in Hermansky-Pudlak Syndrome Type-1: A Possible Connection to Pulmonary Fibrosis. PLoS One 11:e0159177
Metcalfe, Dean D; Pawankar, Ruby; Ackerman, Steven J et al. (2016) Biomarkers of the involvement of mast cells, basophils and eosinophils in asthma and allergic diseases. World Allergy Organ J 9:7
Hox, Valerie; O'Connell, Michael P; Lyons, Jonathan J et al. (2016) Diminution of signal transducer and activator of transcription 3 signaling inhibits vascular permeability and anaphylaxis. J Allergy Clin Immunol 138:187-99
Siebenhaar, F; von Tschirnhaus, E; Hartmann, K et al. (2016) Development and validation of the mastocytosis quality of life questionnaire: MC-QoL. Allergy 71:869-77

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