Evidence map›Paper›PMID 34009545›Full record

ArticleJournal of clinical immunology2021

Decreased ATM Function Causes Delayed DNA Repair and Apoptosis in Common Variable Immunodeficiency Disorders.

Chantal E Hargreaves, Silvia Salatino, Sarah C Sasson, James E G Charlesworth, Elizabeth Bateman, Arzoo M Patel, Consuelo Anzilotti, John Broxholme, Julian C Knight, Smita Y Patel

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

Article in Journal of clinical immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 35% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

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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

10 authors at 6 institutions in 1 country.

Chantal E HargreavesNuffield Department of Medicine and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, OX3 9DU, UK. chantal.hargreaves@ndm.ox.ac.uk.
Silvia SalatinoWellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Sarah C SassonNuffield Department of Medicine and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, OX3 9DU, UK.
James E G CharlesworthOxford University Clinical Academic Graduate School, Medical Sciences Office, John Radcliffe Hospital, University of Oxford, OX3 9DU, Oxford, UK.
Elizabeth BatemanDepartment of Immunology, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, OX3 7LE, UK.
Arzoo M PatelNuffield Department of Medicine and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, OX3 9DU, UK.
Consuelo AnzilottiClinical Immunology Department, Oxford University Hospitals Trust, Oxford, OX3 9DU, UK.
John BroxholmeWellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Julian C KnightWellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Smita Y PatelNuffield Department of Medicine and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, OX3 9DU, UK.
University of Oxford · GBCentre for Human Genetics · GBOxford BioMedica (United Kingdom) · GBChurchill Hospital · GBJohn Radcliffe Hospital · GBOxford University Hospitals NHS Trust · GB

Funding

Cancer Research UK 30137Department of HealthWellcome TrustWellcome Trust 109692/Z/15/ZWellcome Trust 203141/Z/16/ZWellcome Trust 204969/Z/16/Z
6 · The paper itself

Abstract

purposeCommon variable immunodeficiency disorders (CVID) is characterized by low/absent serum immunoglobulins and susceptibility to bacterial infection. Patients can develop an infections-only phenotype or a complex disease course with inflammatory, autoimmune, and/or malignant complications. We hypothesized that deficient DNA repair mechanisms may be responsible for the antibody deficiency and susceptibility to inflammation and cancer in some patients.

methodsGermline variants were identified following targeted sequencing of n = 252 genes related to DNA repair in n = 38 patients. NanoString nCounter PlexSet assay measured gene expression in n = 20 CVID patients and n = 7 controls. DNA damage and apoptosis were assessed by flow cytometry in n = 34 CVID patients and n = 11 controls.

resultsTargeted sequencing supported enrichment of rare genetic variants in genes related to DNA repair pathways with novel and rare likely pathogenic variants identified and an altered gene expression signature that distinguished patients from controls and complex patients from those with an infections-only phenotype. Consistent with this, flow cytometric analyses of lymphocytes following DNA damage revealed a subset of CVID patients whose immune cells have downregulated ATM, impairing the recruitment of other repair factors, delaying repair and promoting apoptosis.

conclusionThese data suggest that germline genetics and altered gene expression predispose a subset of CVID patients to increased sensitivity to DNA damage and reduced DNA repair capacity.

Indexed as

AdultAgedAged, 80 and overApoptosisAtaxia Telangiectasia Mutated ProteinsCase-Control StudiesCommon Variable ImmunodeficiencyDNA DamageDNA RepairFemaleGene ExpressionHumansMaleMiddle AgedPhenotypeYoung AdultAtaxia Telangiectasia Mutated ProteinsATM protein, humanApoptosiscommon variable immunodeficiency disordersCVIDDNA damage and repairprimary antibody deficiency

Identifiers

PMID34009545
PMCPMC8310859
OpenAlexW3160633895

What OpenQuestion holds

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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.