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Record W2159504684 · doi:10.1038/gene.2014.6

MHC associations with clinical and autoantibody manifestations in European SLE

2014· review· en· W2159504684 on OpenAlexaff
David Morris, Maria Michelle Fernando, Kimberly E. Taylor, Sharon A. Chung, Joanne Nititham, Marta E. Alarcón‐Riquelme, Lisa F. Barcellos, Timothy W. Behrens, Chris Cotsapas, Patrick M. Gaffney, Robert Graham, Bernardo A. Pons‐Estel, Peter K. Gregersen, John B. Harley, Stephen L. Hauser, Gary Hom, Carl D. Langefeld, Janelle A. Noble, John D. Rioux, Michael F. Seldin, Timothy J. Vyse, Lindsey A. Criswell

Bibliographic record

VenueGenes and Immunity · 2014
Typereview
Languageen
FieldMedicine
TopicSystemic Lupus Erythematosus Research
Canadian institutionsMontreal Heart InstituteUniversité de Montréal
FundersNational Center for Research ResourcesNational Institute of Dental and Craniofacial ResearchInstituto de Salud Carlos IIIUniversity of California, San FranciscoNational Institutes of HealthNational Institute of Mental HealthVetenskapsrådetEuropean Science FoundationNational Center for Advancing Translational SciencesNational Human Genome Research InstituteWellcome TrustLupus Research AllianceRheumatology Research FoundationU.S. Department of DefenseEuropean CommissionUniversity of PittsburghNational Institute of General Medical SciencesMassachusetts General HospitalU.S. Department of Veterans AffairsNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institute of Allergy and Infectious DiseasesVersus Arthritis
KeywordsAutoantibodyImmunologyMajor histocompatibility complexBiologyHuman leukocyte antigenAllelePhenotypeSingle-nucleotide polymorphismAntibodyAutoimmunityGenotypeGeneticsAntigenGene

Abstract

fetched live from OpenAlex

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the highest number and most statistically significant associations. HLA-DRB1*03:01 was significantly associated with both sub-phenotypes. We found evidence of associations independent of MHC class II variants in the anti-Ro subset alone. Conditional analyses showed that anti-Ro and anti-La subsets are independently associated with HLA-DRB1*0301, and that the HLA-DRB1*03:01 association with SLE is largely but not completely driven by the association of this allele with these sub-phenotypes. Our results provide strong evidence for a multilevel risk model for HLA-DRB1*03:01 in SLE, where the association with anti-Ro and anti-La antibody-positive SLE is much stronger than SLE without these autoantibodies.

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)0.001
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: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.003
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0030.004
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.001
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 head0.108
GPT teacher head0.428
Teacher spread0.319 · 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 designNot applicable
Domainnot available
GenreReview

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

Citations90
Published2014
Admission routes1
Has abstractyes

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