Evidence map›Paper›PMID 36402602›Full record

ArticleJournal of autoimmunity2023

NFκB pathway dysregulation due to reduced RelB expression leads to severe autoimmune disorders and declining immunity.

Nigel Sharfe, Ilan Dalal, Zahra Naghdi, Diane Lefaudeux, Linda Vong, Harjit Dadi, Hector Navarro, Diana Tasher, Adi Ovadia, Tzili Zangen and 4 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of autoimmunity, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.6field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Inherited human RelB deficiency impairs innate and adaptive immunity to infection.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  6. Article
  7. Article
  8. Article
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 3 countries.

Nigel SharfeThe Canadian Centre for Primary Immunodeficiency, Immunogenomic Laboratory, Jeffrey Modell Research Laboratory for the Diagnosis of Primary Immunodeficiency, Division of Immunology/Allergy, Department of Pediatrics, Hospital for Sick Children, and the University of Toronto, Toronto, Ontario, Canada.
Ilan DalalPediatric Department, E. Wolfson Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: ilandalal@hotmail.com.
Zahra NaghdiThe Canadian Centre for Primary Immunodeficiency, Immunogenomic Laboratory, Jeffrey Modell Research Laboratory for the Diagnosis of Primary Immunodeficiency, Division of Immunology/Allergy, Department of Pediatrics, Hospital for Sick Children, and the University of Toronto, Toronto, Ontario, Canada.
Diane LefaudeuxSignaling Systems Laboratory, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA.
Linda VongThe Canadian Centre for Primary Immunodeficiency, Immunogenomic Laboratory, Jeffrey Modell Research Laboratory for the Diagnosis of Primary Immunodeficiency, Division of Immunology/Allergy, Department of Pediatrics, Hospital for Sick Children, and the University of Toronto, Toronto, Ontario, Canada.
Harjit DadiThe Canadian Centre for Primary Immunodeficiency, Immunogenomic Laboratory, Jeffrey Modell Research Laboratory for the Diagnosis of Primary Immunodeficiency, Division of Immunology/Allergy, Department of Pediatrics, Hospital for Sick Children, and the University of Toronto, Toronto, Ontario, Canada.
Hector NavarroSignaling Systems Laboratory, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA.
Diana TasherPediatric Department, E. Wolfson Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Adi OvadiaPediatric Department, E. Wolfson Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Tzili ZangenPediatric Department, E. Wolfson Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Dorit AterPediatric Pulmonology Unit, Assuta Medical Center, Tel Aviv, Israel.
Bo NganDepartment of Laboratory Medicine and Pathobiology, Hospital for Sick Children, Toronto, Ontario, Canada.
Alexander HoffmannSignaling Systems Laboratory, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA.
Chaim M RoifmanThe Canadian Centre for Primary Immunodeficiency, Immunogenomic Laboratory, Jeffrey Modell Research Laboratory for the Diagnosis of Primary Immunodeficiency, Division of Immunology/Allergy, Department of Pediatrics, Hospital for Sick Children, and the University of Toronto, Toronto, Ontario, Canada. Electronic address: chaim.roifman@sickkids.ca.
Hospital for Sick Children · CAUniversity of California, Los Angeles · USUniversity of Toronto · CAWolfson Medical Center · ILAssuta Medical Center · ILTel Aviv University · IL

Funding

The NFkB System in Dendritic CellsR01AI127867 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HOFFMANN, ALEXANDER · 2018 to 2022
$2.2M
Roles of RelB in tuning inflammatory and innate immune responsesR21AI128646 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HOFFMANN, ALEXANDER · 2017 to 2018
$424k
NIAID NIH HHS R01 AI127867NIAID NIH HHS R21 AI128646
6 · The paper itself

Abstract

backgroundGenetic aberrations in the NFκB pathway lead to primary immunodeficiencies with various degrees of severity. We previously demonstrated that complete ablation of the RelB transcription factor, a key component of the alternative pathway, results in an early manifested combined immunodeficiency requiring stem cell transplantation.

objectiveTo study the molecular basis of a progressive severe autoimmunity and immunodeficiency in three patients.

methodsWhole exome sequencing was performed to identify the genetic defect. Molecular and cellular techniques were utilized to assess the variant impact on NFκB signaling, canonical and alternative pathway crosstalk, as well as the resultant effects on immune function.

resultsPatients presented with multiple autoimmune progressive severe manifestations encompassing the liver, gut, lung, and skin, becoming debilitating in the second decade of life. This was accompanied by a deterioration of the immune system, demonstrating an age-related decline in naïve T cells and responses to mitogens, accompanied by a gradual loss of all circulating CD19

conclusionIncomplete loss of RelB provided a unique opportunity to gain insights into NFκB's pathway interactions as well as the pathogenesis of autoimmunity. The P364L RelB mutation leads to gradual decline in immune function with progression of severe debilitating autoimmunity.

Indexed as

Autoimmune DiseasesTranscription Factor RelBGene Expression RegulationHumansNF-kappa BSignal TransductionNF-kappa BTranscription Factor RelBAutoimmunityCombined immunodeficiencyMemory B cellsNaïve T cellsNFκB pathwayRelB

Identifiers

PMID36402602
PMCPMC10861023
OpenAlexW4309438117

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.