TY - JOUR
T1 - Prolonged treatment of peanut-allergic mice with bortezomib significantly reduces serum anti-peanut IgE but does not affect allergic symptoms
AU - Moutsoglou, Daphne M.
AU - Dreskin, Stephen C.
N1 - Publisher Copyright:
© 2016 S. Karger AG, Basel. Copyright: All rights reserved.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Background: Anti-peanut immunoglobulin E (anti-Pn IgE) can persist throughout life, suggesting that this condition could be maintained by long-lived antibody-secreting cells (ASCs). To determine the role of long-lived ASCs, peanut-allergic mice underwent prolonged treatment with the proteasome inhibitor, bortezomib (Bz). Methods: Intravenous Bz was given twice weekly for 21 weeks to peanut-allergic mice. During treatment, serum anti-Pn IgE was measured, and the mice were rechallenged at the end of treatment. Cell populations were measured, and Pn-specific IgG, total IgG, and total IgE ASCs were enumerated in the bone marrow (BM) and spleen (SPL). Results: Prolonged treatment with Bz significantly reduced serum anti-Pn IgE and IgG1 but did not affect symptoms following challenge with Pn, even in mice with undetectable serum anti-Pn IgE. Numbers of CD138+ cells were significantly reduced in the BM but were unaffected in the SPL. Unexpectedly, Bz did not affect numbers of Pn-specific IgG, total IgG, or total IgE ASCs in either the BM or SPL. Conclusions: Cells that maintain long-lived serum anti-Pn IgE are sensitive to Bz. However, prolonged depletion of serum Pn-specific IgE does not result in a decrease of symptoms following challenge with Pn.
AB - Background: Anti-peanut immunoglobulin E (anti-Pn IgE) can persist throughout life, suggesting that this condition could be maintained by long-lived antibody-secreting cells (ASCs). To determine the role of long-lived ASCs, peanut-allergic mice underwent prolonged treatment with the proteasome inhibitor, bortezomib (Bz). Methods: Intravenous Bz was given twice weekly for 21 weeks to peanut-allergic mice. During treatment, serum anti-Pn IgE was measured, and the mice were rechallenged at the end of treatment. Cell populations were measured, and Pn-specific IgG, total IgG, and total IgE ASCs were enumerated in the bone marrow (BM) and spleen (SPL). Results: Prolonged treatment with Bz significantly reduced serum anti-Pn IgE and IgG1 but did not affect symptoms following challenge with Pn, even in mice with undetectable serum anti-Pn IgE. Numbers of CD138+ cells were significantly reduced in the BM but were unaffected in the SPL. Unexpectedly, Bz did not affect numbers of Pn-specific IgG, total IgG, or total IgE ASCs in either the BM or SPL. Conclusions: Cells that maintain long-lived serum anti-Pn IgE are sensitive to Bz. However, prolonged depletion of serum Pn-specific IgE does not result in a decrease of symptoms following challenge with Pn.
KW - Anaphylaxis
KW - Antibody-secreting cell
KW - Immunoglobulin E
KW - Mast cell
KW - Proteasome inhibitor
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U2 - 10.1159/000449247
DO - 10.1159/000449247
M3 - Article
C2 - 27705966
AN - SCOPUS:84990192592
VL - 170
SP - 257
EP - 261
JO - International Archives of Allergy and Immunology
JF - International Archives of Allergy and Immunology
SN - 1018-2438
IS - 4
ER -