MétaCan
Menu
Back to cohort
Record W3132953708 · doi:10.1126/scitranslmed.aav5928

Platelets release mitochondrial antigens in systemic lupus erythematosus

2021· article· en· W3132953708 on OpenAlexafffund
Imène Melki, Isabelle Allaeys, Nicolas Tessandier, Tania Lévesque, Nathalie Cloutier, Audrée Laroche, Nathalie Vernoux, Yann Becker, Hadrien Benk-Fortin, Anne Zufferey, Emmanuelle Rollet‐Labelle, Marc Pouliot, Guy G. Poirier, Natacha Patey, Clémence Belleannée, Denis Soulet, Steven E. McKenzie, Alain Brisson, Marie‐Ève Tremblay, Christian Lood, Paul R. Fortin, Éric Boilard

Bibliographic record

VenueScience Translational Medicine · 2021
Typearticle
Languageen
FieldMedicine
TopicSystemic Lupus Erythematosus Research
Canadian institutionsUniversité LavalCentre Hospitalier Universitaire Sainte-JustineCentre hospitalier de l'Université LavalUniversity of VictoriaCentre hospitalier universitaire de Québec
FundersCanadian Institutes of Health ResearchCanada Research ChairsArthritis SocietyLupus Research Alliance
KeywordsPlateletImmunologyImmune systemMitochondrionBiologyAntigenIn vivoAutoantibodyLupus erythematosusCell biologyAntibody

Abstract

fetched live from OpenAlex

The accumulation of DNA and nuclear components in blood and their recognition by autoantibodies play a central role in the pathophysiology of systemic lupus erythematosus (SLE). Despite the efforts, the sources of circulating autoantigens in SLE are still unclear. Here, we show that in SLE, platelets release mitochondrial DNA, the majority of which is associated with the extracellular mitochondrial organelle. Mitochondrial release in patients with SLE correlates with platelet degranulation. This process requires the stimulation of platelet FcγRIIA, a receptor for immune complexes. Because mice lack FcγRIIA and murine platelets are completely devoid of receptor capable of binding IgG-containing immune complexes, we used transgenic mice expressing FcγRIIA for our in vivo investigations. FcγRIIA expression in lupus-prone mice led to the recruitment of platelets in kidneys and to the release of mitochondria in vivo. Using a reporter mouse with red fluorescent protein targeted to the mitochondrion, we confirmed platelets as a source of extracellular mitochondria driven by FcγRIIA and its cosignaling by the fibrinogen receptor α2bβ3 in vivo. These findings suggest that platelets might be a key source of mitochondrial antigens in SLE and might be a therapeutic target for treating SLE.

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)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Case report · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.755
Threshold uncertainty score0.758

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.003
Science and technology studies0.0000.001
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 head0.031
GPT teacher head0.324
Teacher spread0.293 · 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 designCase report
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

Citations122
Published2021
Admission routes2
Has abstractyes

Explore more

Same venueScience Translational MedicineSame topicSystemic Lupus Erythematosus ResearchFrench-language works237,207