4.6 Article

Immune changes beyond Th2 pathways during rapid multifood immunotherapy enabled with omalizumab

期刊

ALLERGY
卷 76, 期 9, 页码 2809-2826

出版社

WILEY
DOI: 10.1111/all.14833

关键词

biologics; food allergy; IgE; immunotherapy and tolerance induction; immunotherapy clinical; lymphocytes

资金

  1. NIH NIAID AADCRC [U19AI104209, R01AI140134-02, 5UM2AI130836-04, U01 AI140498-03, R01AI119918, 5T32AI007512]
  2. Friend Family Foundation
  3. Crown Family Foundation
  4. Sean N Parker Center for Allergy and Asthma Research at Stanford University
  5. Simons Foundation
  6. Myra Reinhard Foundation
  7. Carell Family Foundation
  8. Food Allergy Research and Education (FARE) Center of Excellence
  9. Department of Pathology and Department of Pediatrics, Stanford University

向作者/读者索取更多资源

The study found that adjunctive anti-IgE treatment with oral immunotherapy can reduce inflammatory cytokines and specific immune cell populations, producing positive effects during desensitization.
Background Multifood oral immunotherapy (mOIT) with adjunctive anti-IgE (omalizumab, XOLAIR(R)) 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 gamma delta 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.

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