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Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Patients With Atopic Dermatitis

2019· preprint· en· W4212801675 on OpenAlexaff
Chris Callewaert, Rob Knight, Teruaki Nakatsuji, Tomasz Kościółek, Paul F. Kotol, Marius Ardeleanu, Emma Guttman‐Yassky, Robert Bissonnette, Jonathan I. Silverberg, James M. Krueger, Neil M.H. Graham, Jennifer D. Hamilton, Claire Clibborn, Alessandro Sorrentino, Richard L. Gallo

Bibliographic record

Venuenot available
Typepreprint
Languageen
FieldMedicine
TopicDermatology and Skin Diseases
Canadian institutionsInnovaderm (Canada)
Fundersnot available
KeywordsAtopic dermatitisStaphylococcus aureusColonizationDupilumabMicrobiologyStaphylococcusDermatologyMedicineBiologyBacteriaGenetics

Abstract

fetched live from OpenAlex

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with Staphylococcus aureus (SA) colonization. Dupilumab (DPL), an anti-IL-4Ru03b1 mAb that inhibits signaling of IL-4/IL-13, key drivers of Type 2/Th2 inflammation, is approved for patients aged u226512 years in the USA with moderate-to-severe AD inadequately controlled by topical prescription treatments or when those therapies are not advisable, adult AD patients in Japan not adequately controlled with existing therapies, and adults with moderate-to-severe AD in Europe who are candidates for systemic therapy. We investigated DPL treatment in AD influences skin colonization by SA and skin microbiome diversity. In a phase 2 trial (NCT01979016), 54 adults with moderate-to-severe AD were randomized (1:1) to weekly subcutaneous injections with DPL 200mg or placebo (PBO) for 16 weeks. SA absolute abundance was assessed by qPCR and relative microbial composition by 16S rRNA sequencing. AD severity was assessed by the Eczema Area and Severity Index (EASI). Serum biomarkers (CCL17, CCL18, and IgE) were measured. At baseline, SA had higher absolute abundance on lesional vs non-lesional skin (P<0.05). Lesional skin showed a distinct cluster in microbial u03b2-diversity (P<0.001) and lower u03b1-diversity (P<0.05). DPL decreased SA absolute and relative abundance while overall microbial diversity increased. DPL improved EASI scores and decreased serum biomarkers. No major changes were noted with PBO. Improved EASI and serum biomarkers strongly correlated with decreased SA abundance (P<0.001). These results reveal strong links between SA, the skin microbial community, serum biomarkers, and AD severity, and demonstrate that targeted suppression of Type 2 immunity by anti-IL-4Ru03b1 mAb improves the skin microbial community.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.008
GPT teacher head0.217
Teacher spread0.209 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations1
Published2019
Admission routes1
Has abstractyes

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