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Record W4400871372 · doi:10.1016/j.jacig.2024.100310

Effect of benralizumab on inflammation in skin after intradermal allergen challenge in patients with moderate-to-severe atopic dermatitis

2024· article· en· W4400871372 on OpenAlexafffund
Christiane E. Whetstone, Ruth P. Cusack, Emma Price, Karen Howie, Dhuha Al‐Sajee, Sue Beaudin, Jennifer Wattie, Nadia Alsaji, Abbey Schlatman, Vanessa Luk, Xiaotian Ju, Paul M. O’Byrne, M INMAN, Roma Sehmi, Hermenio Lima, Gail M. Gauvreau

Bibliographic record

VenueJournal of Allergy and Clinical Immunology Global · 2024
Typearticle
Languageen
FieldMedicine
TopicDermatology and Skin Diseases
Canadian institutionsMcMaster University
FundersAstraZeneca CanadaAstraZeneca
KeywordsAtopic dermatitisMedicineBenralizumabDermatologyEosinophiliaAllergenImmunologyAllergyEosinophilAsthma

Abstract

fetched live from OpenAlex

Background Atopic dermatitis (AD) is a skin barrier dysfunction characterized by tissue eosinophilia. Objective In patients with AD, we evaluated the effect of eosinophil depletion with benralizumab on markers of inflammation in skin after intradermal allergen challenge. Methods A total of 20 patients with moderate-to-severe AD completed a randomized, double-blind, placebo-controlled parallel-group study comparing 3 doses of benralizumab (30 mg each) administered subcutaneously every 4 weeks (n = 9) with placebo (n = 11). Allergen and saline control intradermal challenges were conducted before and after treatment, with skin biopsy samples collected 24 hours after challenge. Early and late cutaneous responses were measured by skin wheal size. Levels of eosinophils and IL-5 receptor-α–bearing cells, including eosinophil progenitor (EoP) cells, basophils, and mast cells, in papillary dermis were measured by immunofluorescence microscopy, and levels of EoP cells, hematopoietic progenitor cells, and type 2 innate lymphoid cells in the blood were measured by flow cytometry. Outcomes were compared between the placebo and benralizumab treatment groups by using the Mann-Whitney U test. Results Benralizumab reduced eosinophil counts in the blood ( P < .0001) and allergen-challenged skin, as measured by hematoxylin and eosin staining and eosinophil cationic protein antibody concentration ( P < .05). Benralizumab lowered the levels of EoP cells, mast cells, and basophils in the skin, as well as the levels of EoP cells, hematopoietic progenitor cells, and type 2 innate lymphoid cells in the blood (all P < .05). There was a trend toward improvement in the early cutaneous response ( P = .095) but no effect on the late cutaneous response. Conclusion In patients with moderate-to-severe AD, benralizumab treatment significantly inhibited accumulation of eosinophils and other IL-5 receptor-α–expressing cells in the papillary dermis after intradermal allergen challenge. Targeting IL-5 receptor-α–positive cells did not modulate the size of the allergen-induced skin wheal (ClincialTrials.gov identifier NCT03563066).

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.079
Threshold uncertainty score0.444

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.006
GPT teacher head0.286
Teacher spread0.280 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations5
Published2024
Admission routes2
Has abstractyes

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