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Record W2529710156 · doi:10.1038/ncomms13027

Loss of immune tolerance to IL-2 in type 1 diabetes

2016· article· en· W2529710156 on OpenAlexafffund
Louis Pérol, John M. Lindner, Pamela Caudana, Nicolás Gonzalo Núñez, Audrey Baeyens, Andrea Valle, Christine Sedlik, Delphine Loirat, Olivier Boyer, Alain Créange, José L. Cohen, Ute C. Rogner, Jun Yamanouchi, Martine Marchant, Xavier Charles Leber, Meike Scharenberg, Marie‐Claude Gagnerault, Roberto Mallone, Manuela Battaglia, Pere Santamaría, Agnès Hartemann, Elisabetta Traggiai, Eliane Piaggio

Bibliographic record

VenueNature Communications · 2016
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDiabetes and associated disorders
Canadian institutionsUniversity of Calgary
FundersCanadian Institutes of Health ResearchDirection Générale de l’offre de SoinsCentre National de la Recherche ScientifiqueAstraZenecaEuropean Foundation for the Study of DiabetesAgence Nationale de la RechercheInstitut National de la Santé et de la Recherche MédicaleAlberta InnovatesUniversidad Nacional de Rosario
KeywordsType 2 diabetesImmune systemDiabetes mellitusImmune toleranceType 1 diabetesMedicineImmunologyBiologyEndocrinology

Abstract

fetched live from OpenAlex

Type 1 diabetes (T1D) is characterized by a chronic, progressive autoimmune attack against pancreas-specific antigens, effecting the destruction of insulin-producing β-cells. Here we show interleukin-2 (IL-2) is a non-pancreatic autoimmune target in T1D. Anti-IL-2 autoantibodies, as well as T cells specific for a single orthologous epitope of IL-2, are present in the peripheral blood of non-obese diabetic (NOD) mice and patients with T1D. In NOD mice, the generation of anti-IL-2 autoantibodies is genetically determined and their titre increases with age and disease onset. In T1D patients, circulating IgG memory B cells specific for IL-2 or insulin are present at similar frequencies. Anti-IL-2 autoantibodies cloned from T1D patients demonstrate clonality, a high degree of somatic hypermutation and nanomolar affinities, indicating a germinal centre origin and underscoring the synergy between cognate autoreactive T and B cells leading to defective immune tolerance.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
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)0.0010.000

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 head0.006
GPT teacher head0.260
Teacher spread0.254 · 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

Citations42
Published2016
Admission routes2
Has abstractyes

Explore more

Same venueNature Communications→Same topicDiabetes and associated disorders→French-language works237,207→