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Record W4391116455 · doi:10.1136/rmdopen-2023-003897

Human leucocyte antigens and Japanese patients with polymyalgia rheumatica: the protective effect of <i>DRB1*09:01</i>

2024· article· en· W4391116455 on OpenAlexfundno aff
Shinichi Nogi, Shomi Oka, Takashi Higuchi, Hiroshi Furukawa, Kota Shimada, Takanori Azuma, Takao Sugiyama, Fuminori Hirano, Akira Okamoto, Misuzu Fujimori, Yoshiro Horai, Atsushi Ihata, Atsushi Hashimoto, Akiko Komiya, Toshihiro Matsui, Naoshi Fukui, Masao Katayama, Kiyoshi Migita, Shigeto Tohma

Bibliographic record

VenueRMD Open · 2024
Typearticle
Languageen
FieldMedicine
TopicSystemic Lupus Erythematosus Research
Canadian institutionsnot available
FundersPfizer JapanChugai PharmaceuticalMitsubishi Tanabe Pharma CorporationTeijin PharmaAstellas Foundation for Research on Metabolic DisordersAstellas PharmaMerck Sharp and DohmeOno PharmaceuticalEisaiDaiichi Sankyo EuropeAsahi Kasei Pharma CorporationPfizerJapan Research Foundation for Clinical PharmacologyAbbott JapanJapan Society for the Promotion of ScienceMitsui Sumitomo Insurance Welfare FoundationMinistry of Health, Labour and WelfareDaiwa Securities Health FoundationBristol-Myers SquibbEisai CanadaNakatomi FoundationTakeda Science FoundationJapan Agency for Medical Research and Development
KeywordsMedicinePolymyalgia rheumaticaInternal medicineGastroenterologyHaplotypeGenotypingHLA-DRB1GenotypeAntigenImmunologyHuman leukocyte antigenDiseaseGeneGiant cell arteritisGenetics

Abstract

fetched live from OpenAlex

Objective The hallmarks of the chronic inflammatory disease polymyalgia rheumatica (PMR) include pain, and morning stiffness in areas of the neck, shoulder and pelvic girdle. The human leucocyte antigen ( HLA ) gene was reported to be an important risk factor for PMR, but it has not been analysed precisely, especially in populations other than Europeans. Methods Genotyping of DRB1 and DQB1 was performed in Japanese PMR patients (n=270) and controls (n=413). Associations between allele carrier and genotype frequencies were determined for PMR. Results DRB1*04:05 was associated with a predisposition to PMR (p=0.0006, Pc =0.0193, OR 1.85, 95% CI 1.31 to 2.62). DRB1*09:01 was associated with protection against PMR (p=1.46×10 −5 , Pc =0.0004, OR 0.40, 95% CI 0.26 to 0.61). A shared epitope (SE) associated with PMR (p=3.07×10 −6 , OR 2.11, 95% CI 1.54 to 2.88). DQB1*03:03 (p=0.0010, P c=0.0140, OR 0.52, 95% CI 0.35 to 0.77) was associated with protection against PMR and DQB1*04:01 (p=0.0009, P c=0.0140, OR 1.82, 95% CI 1.28 to 2.58) was associated with predisposition to PMR. A gene dosage effect was observed for DRB1*09:01 and DQB1*03:03 , but not for DRB1*04:05, SE or DQB1*04:01 . Haplotype and logistic regression analyses suggested a protective effect for DRB1*09:01 . Conclusion This study is the first to demonstrate predisposing associations of DRB1*04:05, SE, and DQB1*04:01 , and protective associations of DRB1*09:01 and DQB1*03:03 with PMR in Japanese patients. Our data indicate HLA has predisposing and protective effects on the pathogenesis of PMR.

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 categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.255
Threshold uncertainty score0.389

Codex and Gemma teacher scores by category

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

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 head0.308
Teacher spread0.294 · 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 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

Citations0
Published2024
Admission routes1
Has abstractyes

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