Bortezomib treatment diminishes hazelnut-induced intestinal anaphylaxis in mice.
Food allergy is a common health problem and can cause anaphylaxis. Avoidance of the offending food allergen is still the mainstay therapeutic approach. In this study, we investigated the role of plasma cell reduction by proteasome inhibition in a murine model of food allergy and examined the impact of this treatment on the systemic and local immune response. For this purpose, intestinal anaphylaxis was induced in BALB/c mice with the food allergen hazelnut, in conjunction with different adjuvants (alum and Staphylococcal enterotoxin B SEB) and different administration routes (oral and intraperitoneal). In both models, allergy symptoms were observed, but the clinical severity was more pronounced in the hazelnut-alum model than in the hazelnut-SEB model. Accordingly, allergen-specific immunoglobulin E (IgE) against hazelnut was detectable, and mast cell protease-1 in serum was increased after allergen provocation. Treatment with the proteasome inhibitor bortezomib reduced plasma cells and resulted in an abolishment of hazelnut allergen-specific IgE, which was associated with amelioration of clinical symptoms as well as a significant decrease in both CD19(+) and follicular B lymphocytes. Our data demonstrate the importance of allergen-specific IgE in food allergy and point to B cells as potential therapeutic targets for its treatment.
Department of Dermatology und Allergology, Allergie-Centrum-Charité, Charité - Universitätsmedizin, Berlin, Germany.
Kiran Kumar
KK
Mudnakudu Nagaraju
Department of Dermatology und Allergology, Allergie-Centrum-Charité, Charité - Universitätsmedizin, Berlin, Germany.
Magda
M
Babina
Department of Dermatology und Allergology, Allergie-Centrum-Charité, Charité - Universitätsmedizin, Berlin, Germany.
Christin
C
Weise
Department of Medicine-I for Gastroenterology, Infectious Disease and Rheumatology, Research Center ImmunoSciences, Charité - Universitätsmedizin, Berlin, Germany.
Anja
A
Kühl
Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Universitätsmedizin, Berlin, Germany.
Joerg
J
Schulzke
Department of Dermatology und Allergology, Allergie-Centrum-Charité, Charité - Universitätsmedizin, Berlin, Germany.
Margitta
M
Worm
D000485:Allergens / Q000276:immunology*; D000707:Anaphylaxis / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000069286:Bortezomib / Q000008:administration & dosage / Q000494:pharmacology*; D031211:Corylus / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D005512:Food Hypersensitivity / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007422:Intestines / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D061988:Proteasome Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D012720:Severity of Illness Index
D000485:Allergens; D061988:Proteasome Inhibitors; D007073:Immunoglobulin E; D000069286:Bortezomib
Anaphylaxis; B cells; Food allergy; Immunoglobulin E; Proteasome inhibition