Immune changes beyond Th2 pathways during rapid multifood immunotherapy enabled with omalizumab
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".