Immune changes beyond Th2 pathways during rapid multifood immunotherapy enabled with omalizumab
Monali Manohar, Diane Dunham, Sheena Gupta, Zheng Yan, Wenming Zhang, Samantha Minnicozzi, Matthew Kirkey, Bryan Bunning, Roshni Roy Chowdhury, Stephen J Galli, Scott D Boyd, Laurie Elizabeth Kost, R Sharon Chinthrajah, Manisha Desai, Hans C Oettgen, Holden T Maecker, Wong Yu, Rosemarie H DeKruyff, Sandra Andorf, Kari C Nadeau, Monali Manohar, Diane Dunham, Sheena Gupta, Zheng Yan, Wenming Zhang, Samantha Minnicozzi, Matthew Kirkey, Bryan Bunning, Roshni Roy Chowdhury, Stephen J Galli, Scott D Boyd, Laurie Elizabeth Kost, R Sharon Chinthrajah, Manisha Desai, Hans C Oettgen, Holden T Maecker, Wong Yu, Rosemarie H DeKruyff, Sandra Andorf, Kari C Nadeau
Abstract
Background: Multifood oral immunotherapy (mOIT) with adjunctive anti-IgE (omalizumab, XOLAIR® ) treatment affords safe, effective, and rapid desensitization to multiple foods, although the specific immune mechanisms mediating this desensitization remain to be fully elucidated.
Methods: Participants in our phase 2 mOIT trial (NCT02643862) received omalizumab from baseline to week 16 and mOIT from week 8 to week 36. We compared the immune profile of PBMCs and plasma taken at baseline, week 8, and week 36 using high-dimensional mass cytometry, component-resolved diagnostics, the indirect basophil activation test, and Luminex.
Results: We found (i) decreased frequency of IL-4+ peanut-reactive CD4+ T cells and a marked downregulation of GPR15 expression and CXCR3 frequency among γδ and CD8+ T-cell subsets at week 8 during the initial, omalizumab-alone induction phase; (ii) significant upregulation of the skin-homing receptor CCR4 in peanut-reactive CD4+ T and Th2 effector memory (EM) cells and of cutaneous lymphocyte-associated antigen (CLA) in peanut-reactive CD8+ T and CD8+ EM cells; (iii) downregulation of CD86 expression among antigen-presenting cell subsets; and (iv) reduction in pro-inflammatory cytokines, notably IL-17, at week 36 post-OIT. We also observed significant attenuation of the Th2 phenotype post-OIT, defined by downregulation of IL-4 peanut-reactive T cells and OX40 in Th2EM cells, increased allergen component-specific IgG4/IgE ratio, and decreased allergen-driven activation of indirectly sensitized basophils.
Conclusions: This exploratory study provides novel comprehensive insight into the immune underpinnings of desensitization through omalizumab-facilitated mOIT. Moreover, this study provides encouraging results to support the complex immune changes that can be induced by OIT.
Keywords: IgE; biologics; food allergy; immunotherapy and tolerance induction; immunotherapy clinical; lymphocytes.
© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
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Source: PubMed