Evidence map›Paper›PMID 25569260›Full record

ArticleGenes and immunity2015

A mutation in caspase-9 decreases the expression of BAFFR and ICOS in patients with immunodeficiency and lymphoproliferation.

N Clemente, E Boggio, C L Gigliotti, E Orilieri, G Cappellano, E Toth, P A Valletti, C Santoro, I Quinti, C Pignata and 6 more

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Article in Genes and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 41% 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

3 citing papers in PubMed, 8 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

16 authors at 4 institutions in 2 countries.

N ClementeInterdisciplinary Research Center of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Eastern Piedmont 'A Avogadro', Novara, Italy.
E BoggioInterdisciplinary Research Center of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Eastern Piedmont 'A Avogadro', Novara, Italy.
C L GigliottiInterdisciplinary Research Center of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Eastern Piedmont 'A Avogadro', Novara, Italy.
E OrilieriInterdisciplinary Research Center of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Eastern Piedmont 'A Avogadro', Novara, Italy.
G CappellanoInterdisciplinary Research Center of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Eastern Piedmont 'A Avogadro', Novara, Italy.
E TothInterdisciplinary Research Center of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Eastern Piedmont 'A Avogadro', Novara, Italy.
P A VallettiInterdisciplinary Research Center of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Eastern Piedmont 'A Avogadro', Novara, Italy.
C SantoroInterdisciplinary Research Center of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Eastern Piedmont 'A Avogadro', Novara, Italy.
I QuintiDepartment of Clinical Immunology, University of Rome 'La Sapienza', Rome, Italy.
C PignataDepartment of Pediatrics, 'Federico II' University, Naples, Italy.
L D NotarangeloDivision of Immunology, Children's Hospital, Harvard Medical School, Boston, MA, USA.
C DianzaniDepartment of Drug Science and Technology, University of Turin, Turin, Italy.
I DianzaniInterdisciplinary Research Center of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Eastern Piedmont 'A Avogadro', Novara, Italy.
U RamenghiDepartment of Pediatrics, University of Turin, Turin, Italy.
U DianzaniInterdisciplinary Research Center of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Eastern Piedmont 'A Avogadro', Novara, Italy.
A ChiocchettiInterdisciplinary Research Center of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Eastern Piedmont 'A Avogadro', Novara, Italy.
University of Turin · ITFederico II University Hospital · ITHarvard University · USSapienza University of Rome · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lymphocyte apoptosis is mainly induced by either death receptor-dependent activation of caspase-8 or mitochondria-dependent activation of caspase-9. Mutations in caspase-8 lead to autoimmunity/lymphoproliferation and immunodeficiency. This work describes a heterozygous H237P mutation in caspase-9 that can lead to similar disorders. H237P mutation was detected in two patients: Pt1 with autoimmunity/lymphoproliferation, severe hypogammaglobulinemia and Pt2 with mild hypogammaglobulinemia and Burkitt lymphoma. Their lymphocytes displayed defective caspase-9 activity and decreased apoptotic and activation responses. Transfection experiments showed that mutant caspase-9 display defective enzyme and proapoptotic activities and a dominant-negative effect on wild-type caspase-9. Ex vivo analysis of the patients' lymphocytes and in vitro transfection experiments showed that the expression of mutant caspase-9 correlated with a downregulation of BAFFR (B-cell-activating factor belonging to the TNF family (BAFF) receptor) in B cells and ICOS (inducible T-cell costimulator) in T cells. Both patients carried a second inherited heterozygous mutation missing in the relatives carrying H237P: Pt1 in the transmembrane activator and CAML interactor (TACI) gene (S144X) and Pt2 in the perforin (PRF1) gene (N252S). Both mutations have been previously associated with immunodeficiencies in homozygosis or compound heterozygosis. Taken together, these data suggest that caspase-9 mutations may predispose to immunodeficiency by cooperating with other genetic factors, possibly by downregulating the expression of BAFFR and ICOS.

Indexed as

MutationAdolescentAdultApoptosisB-Cell Activation Factor ReceptorCaspase 9Down-RegulationHEK293 CellsHumansImmunologic Deficiency SyndromesInducible T-Cell Co-Stimulator ProteinLymphoproliferative DisordersMalePedigreeB-Cell Activation Factor ReceptorCASP9 protein, humanCaspase 9ICOS protein, humanInducible T-Cell Co-Stimulator ProteinTNFRSF13C protein, human

Identifiers

PMID25569260
OpenAlexW2035926805

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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.