Prolonged Treatment of Peanut-Allergic Mice with Bortezomib Significantly Reduces Serum Anti-Peanut IgE but Does Not Affect Allergic Symptoms

Abstract

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.

Non-classical B Cell Memory of Allergic IgE Responses

“…Treatment with the proteasome inhibitor bortezomib to deplete IgE plasma cells has provided more ambiguous results, in one case reducing circulating IgE and plasma cells but not allergy (102), and in another two studies, reducing IgE and suppressing allergic reactivity (103, 104). The variable results described in studies targeting plasma cells with bortezomib could be due to different sensitivities of plasma cells populations, and to an effect of plasma cells rebounding after plasma cell depletion (105).…”

Recent Advances in Experimental Allergy

“…This work highlights the potential of DNA vaccines as therapy for peanut allergy (and other food allergies) as both prophylaxis and treatment. Furthermore, pretreatment with PLL may be a strategy to overcome low immunogenicity that has often proved a hurdle to DNA vaccine efficacy [61, 62]. …”