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Record W4284709246 · doi:10.1183/13993003.01469-2021

Plasma cell but not CD20-mediated B-cell depletion protects from bleomycin-induced lung fibrosis

2022· article· en· W4284709246 on OpenAlexaff
Cecilia M. Prêle, Tylah Miles, David R. Pearce, Robert J.J. O’Donoghue, Christopher Grainge, Lucy Barrett, Kimberly A. Birnie, Andrew Lucas, Svetlana Baltic, Matthias Ernst, Catherine Rinaldi, Geoffrey J. Laurent, Darryl A. Knight, Mark W. Fear, Gerard F. Hoyne, Robin J. McAnulty, Steven E. Mutsaers

Bibliographic record

VenueEuropean Respiratory Journal · 2022
Typearticle
Languageen
FieldMedicine
TopicInterstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Canadian institutionsProvidence Health Care Research Institute
FundersBritish Lung FoundationMurdoch UniversityMedical Research CouncilGenentechNational Health and Medical Research CouncilLung Foundation Australia
KeywordsBleomycinIdiopathic pulmonary fibrosisMedicinePulmonary fibrosisFibrosisLungCD20Cancer researchImmune systemBortezomibPathologyCD19ImmunologyChemotherapyInternal medicineLymphoma

Abstract

fetched live from OpenAlex

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with chronic inflammation and tissue remodelling leading to fibrosis, reduced pulmonary function, respiratory failure and death. Bleomycin (Blm)-induced lung fibrosis in mice replicates several clinical features of human IPF, including prominent lymphoid aggregates of predominantly B-cells that accumulate in the lung adjacent to areas of active fibrosis. We have shown previously a requirement for B-cells in the development of Blm-induced lung fibrosis in mice. To determine the therapeutic potential of inhibiting B-cell function in pulmonary fibrosis, we examined the effects of anti-CD20 B-cell ablation therapy to selectively remove mature B-cells from the immune system and inhibit Blm-induced lung fibrosis. Anti-CD20 B-cell ablation did not reduce fibrosis in this model; however, immune phenotyping of peripheral blood and lung resident cells revealed that anti-CD20-treated mice retained a high frequency of CD19 + CD138 + plasma cells. Interestingly, high levels of CD138 + cells were also identified in the lung tissue of patients with IPF, consistent with the mouse model. Treatment of mice with bortezomib, which depletes plasma cells, reduced the level of Blm-induced lung fibrosis, implicating plasma cells as important effector cells in the development and progression of pulmonary fibrosis.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
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 score0.664
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.002
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 head0.018
GPT teacher head0.230
Teacher spread0.212 · 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.

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

Citations71
Published2022
Admission routes1
Has abstractyes

Explore more

Same venueEuropean Respiratory JournalSame topicInterstitial Lung Diseases and Idiopathic Pulmonary FibrosisFrench-language works237,207