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Record W4388976184 · doi:10.1038/s41467-023-43504-8

The extrafollicular B cell response is a hallmark of childhood idiopathic nephrotic syndrome

2023· article· en· W4388976184 on OpenAlexafffund
Tho-Alfakar Al-Aubodah, Lamine Aoudjit, Giuseppe Pascale, Maneka A. Perinpanayagam, David Langlais, Martin Bitzan, Susan Samuel, Ciriaco A. Piccirillo, Tomoko Takano

Bibliographic record

VenueNature Communications · 2023
Typearticle
Languageen
FieldMedicine
TopicRenal Diseases and Glomerulopathies
Canadian institutionsMcGill Genome CentreMcGill UniversityUniversity of CalgaryMcGill University Health Centre
FundersMcGill University Health CentreCanadian Institutes of Health ResearchFonds de Recherche du Québec - SantéKidney Foundation of CanadaGovernment of CanadaMcGill University
KeywordsMarginal zoneBiologyCD11cImmunologyB cellImmune systemFlow cytometryAntibodyPhenotypeGeneticsGene

Abstract

fetched live from OpenAlex

Abstract The efficacy of the B cell-targeting drug rituximab (RTX) in childhood idiopathic nephrotic syndrome (INS) suggests that B cells may be implicated in disease pathogenesis. However, B cell characterization in children with INS remains limited. Here, using single-cell RNA sequencing, we demonstrate that a B cell transcriptional program poised for effector functions represents the major immune perturbation in blood samples from children with active INS. This transcriptional profile was associated with an extrafollicular B cell response marked by the expansion of atypical B cells (atBCs), marginal zone-like B cells, and antibody-secreting cells (ASCs). Flow cytometry of blood from 13 children with active INS and 24 healthy donors confirmed the presence of an extrafollicular B cell response denoted by the expansion of proliferating RTX-sensitive extrafollicular (CXCR5 – ) CD21 low T-bet + CD11c + atBCs and short-lived T-bet + ASCs in INS. Together, our study provides evidence for an extrafollicular origin for humoral immunity in active INS.

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)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.013
GPT teacher head0.286
Teacher spread0.273 · 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 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

Citations39
Published2023
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicRenal Diseases and GlomerulopathiesFrench-language works237,207