Repository logo
 
Publication

Characterization of the Clinical and Immunologic Phenotype and Management of 157 Individuals with 56 Distinct Heterozygous NFKB1 Mutations

2020Journal article Open access
Simple item page
dc.contributor.authorLorenzini, T
dc.contributor.authorFliegauf, M
dc.contributor.authorKlammer, N
dc.contributor.authorFrede, N
dc.contributor.authorProietti, M
dc.contributor.authorBulashevska, A
dc.contributor.authorCamacho-Ordonez, N
dc.contributor.authorVarjosalo, M
dc.contributor.authorKinnunen, M
dc.contributor.authorde Vries, E
dc.contributor.authorvan der Meer, JW
dc.contributor.authorAmeratunga, R
dc.contributor.authorRoifman, CM
dc.contributor.authorSchejter, YD
dc.contributor.authorKobbe, R
dc.contributor.authorHautala, T
dc.contributor.authorAtschekzei, F
dc.contributor.authorSchmidt, RE
dc.contributor.authorSchröder, C
dc.contributor.authorStepensky, P
dc.contributor.authorShadur, B
dc.contributor.authorPedroza, LA
dc.contributor.authorvan der Flier, M
dc.contributor.authorMartínez-Gallo, M
dc.contributor.authorGonzalez-Granado, LI
dc.contributor.authorAllende, LM
dc.contributor.authorShcherbina, A
dc.contributor.authorKuzmenko, N
dc.contributor.authorZakharova, V
dc.contributor.authorNeves, JF
dc.contributor.authorSvec, P
dc.contributor.authorFischer, U
dc.contributor.authorIp, W
dc.contributor.authorBartsch, O
dc.contributor.authorBarış, S
dc.contributor.authorKlein, C
dc.contributor.authorGeha, R
dc.contributor.authorChou, J
dc.contributor.authorAlosaimi, M
dc.contributor.authorWeintraub, L
dc.contributor.authorBoztug, K
dc.contributor.authorHirschmugl, T
dc.contributor.authorDos Santos Vilela, MM
dc.contributor.authorHolzinger, D
dc.contributor.authorSeidl, M
dc.contributor.authorLougaris, V
dc.contributor.authorPlebani, A
dc.contributor.authorAlsina, L
dc.contributor.authorPiquer-Gibert, M
dc.contributor.authorDeyà-Martínez, A
dc.contributor.authorSlade, CA
dc.contributor.authorAghamohammadi, A
dc.contributor.authorAbolhassani, H
dc.contributor.authorHammarström, L
dc.contributor.authorKuismin, O
dc.contributor.authorHelminen, M
dc.contributor.authorAllen, HL
dc.contributor.authorThaventhiran, JE
dc.contributor.authorFreeman, AF
dc.contributor.authorCook, M
dc.contributor.authorBakhtiar, s
dc.contributor.authorChristiansen, M
dc.contributor.authorCunningham-Rundles, C
dc.contributor.authorPatel, NC
dc.contributor.authorRae, W
dc.contributor.authorNiehues, T
dc.contributor.authorBrauer, N
dc.contributor.authorSyrjänen, J
dc.contributor.authorSeppänen, MJ
dc.contributor.authorBurns, SO
dc.contributor.authorTuijnenburg, P
dc.contributor.authorKuijpers, TW
dc.contributor.authorWarnatz, K
dc.contributor.authorGrimbacher, B
dc.date.accessioned2021-06-23T14:39:46Z
dc.date.available2021-06-23T14:39:46Z
dc.date.issued2020
dc.description.abstractBackground: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. Objective: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. Methods: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. Results: We classified 56 of the 105 distinct NFKB1 variants in 157 individuals from 68 unrelated families as pathogenic. Incomplete clinical penetrance (70%) and age-dependent severity of NFKB1-related phenotypes were observed. The phenotype included hypogammaglobulinemia (88.9%), reduced switched memory B cells (60.3%), and respiratory (83%) and gastrointestinal (28.6%) infections, thus characterizing the disorder as primary immunodeficiency. However, the high frequency of autoimmunity (57.4%), lymphoproliferation (52.4%), noninfectious enteropathy (23.1%), opportunistic infections (15.7%), autoinflammation (29.6%), and malignancy (16.8%) identified NF-κB1-related disease as an inborn error of immunity with immune dysregulation, rather than a mere primary immunodeficiency. Current treatment includes immunoglobulin replacement and immunosuppressive agents. Conclusions: We present a comprehensive clinical overview of the NF-κB1-related phenotype, which includes immunodeficiency, autoimmunity, autoinflammation, and cancer. Because of its multisystem involvement, clinicians from each and every medical discipline need to be made aware of this autosomal-dominant disease. Hematopoietic stem cell transplantation and NF-κB1 pathway-targeted therapeutic strategies should be considered in the future.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Allergy Clin Immunol. 2020;146(4):901-911pt_PT
dc.identifier.doi10.1016/j.jaci.2019.11.051pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/3743
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.subjectAdultpt_PT
dc.subjectAgedpt_PT
dc.subjectAutoimmunitypt_PT
dc.subjectBiological Variation, Populationpt_PT
dc.subjectBiomarkerspt_PT
dc.subjectDisease Managementpt_PT
dc.subjectFemalept_PT
dc.subjectFluorescent Antibody Techniquept_PT
dc.subjectHumanspt_PT
dc.subjectImmunohistochemistrypt_PT
dc.subjectKaplan-Meier Estimatept_PT
dc.subjectMagnetic Resonance Imagingpt_PT
dc.subjectMalept_PT
dc.subjectMiddle Agedpt_PT
dc.subjectNF-kappa B p50 Subunitpt_PT
dc.subjectPrognosispt_PT
dc.subjectTomography, X-Ray Computedpt_PT
dc.subjectGenetic Association Studiespt_PT
dc.subjectGenetic Predisposition to Diseasept_PT
dc.subjectHeterozygotept_PT
dc.subjectMutationpt_PT
dc.subjectPhenotypept_PT
dc.subjectHDE PEDpt_PT
dc.titleCharacterization of the Clinical and Immunologic Phenotype and Management of 157 Individuals with 56 Distinct Heterozygous NFKB1 Mutationspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage911pt_PT
oaire.citation.issue4pt_PT
oaire.citation.startPage901pt_PT
oaire.citation.titleThe Journal of allergy and clinical immunologypt_PT
oaire.citation.volume146pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
J Allergy Clin Immunol 2020_146_901.pdf
Size:
3.51 MB
Format:
Adobe Portable Document Format
Download

Collections

PED - Artigos