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Record W2268167744 · doi:10.14785/lymphosign-2015-0014

Heterozygous mutations in RelB can be associated with immune dysregulation and lymphoma

2016· article· en· W2268167744 on OpenAlexafffundvenue
Alison Haynes, Palinder Kamra, Chaim M. Roifman

Bibliographic record

VenueLymphoSign Journal · 2016
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicNF-κB Signaling Pathways
Canadian institutionsSickKids FoundationHospital for Sick ChildrenUniversity of TorontoJaneway Children's Health and Rehabilitation CentreMemorial University of Newfoundland
FundersOntario Ministry of Research and InnovationHospital for Sick ChildrenGenome CanadaOntario GenomicsOntario Genomics InstituteImmunodeficiency CanadaJeffrey Modell Foundation
KeywordsRELBImmune systemImmunologyHaploinsufficiencyLymphomaImmune dysregulationBiologyImmunodeficiencyAntigenCancer researchMedicineTranscription factorGeneticsNFKB1PhenotypeGene

Abstract

fetched live from OpenAlex

Background: The nuclear factor kappa-B (NFκB) family of transcription factors is essential for numerous processes, including the development and function of the innate and adaptive immune response, inflammation and cell growth, differentiation, and survival. Recently, patients with homozygous mutations in the gene for the NFκB transcription factor RelB have been described as presenting with features of combined immunodeficiency such as recurrent infection and failure to thrive as well as reduced response to mitogens and an inability to maintain an adequate antibody response to immunizations. Methods: The immune status and genetics of the parents of patients with homozygous RelB mutations were assessed. In vitro mitogen stimulation, flow cytometry, and cytokine ELISA were used to assess immunological status and signal transduction pathways. Results: Four patients were confirmed to have heterozygous RelB mutations. The majority of patients had evidence of immune dysfunction with impaired in vitro responses to PHA and antigens. One patient developed lymphoma. Conclusion: Heterozygous RelB mutations can be associated with immune dysregulation with impaired mitogen and antigen responses and lymphoma. It is likely that the immune defects apparent in RelB deficient humans are due to a wider effect of RelB on the classical NFκB pathway (involving RelA and c-Rel) through cross-regulation of activation and expression in addition to RelB’s function within the alternate pathway. Statement of novelty: We describe for the first time the immune abnormalities in patients with heterozygous RelB mutations.

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)0.001
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 score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0030.001

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 head0.009
GPT teacher head0.210
Teacher spread0.201 · 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

Citations2
Published2016
Admission routes3
Has abstractyes

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