A great disturbance in the force: IL-2 receptor defects disrupt immune homeostasis

The current review highlights how inborn errors of immunity (IEI) due to IL-2 receptor (IL-2R) subunit defects may result in children presenting with a wide variety of infectious and inflammatory presentations beyond typical X-linked severe combined immune deficiency (X-SCID) associated with IL-2Rγ....

Full description

Saved in:
Bibliographic Details
Published inCurrent opinion in pediatrics Vol. 34; no. 6; p. 580
Main Authors Hernandez, Joseph D, Hsieh, Elena W Y
Format Journal Article
LanguageEnglish
Published United States 01.12.2022
Subjects
Online AccessGet more information

Cover

Loading…
Abstract The current review highlights how inborn errors of immunity (IEI) due to IL-2 receptor (IL-2R) subunit defects may result in children presenting with a wide variety of infectious and inflammatory presentations beyond typical X-linked severe combined immune deficiency (X-SCID) associated with IL-2Rγ. Newborn screening has made diagnosis of typical SCID presenting with severe infections less common. Instead, infants are typically diagnosed in the first days of life when they appear healthy. Although earlier diagnosis has improved clinical outcomes for X-SCID, atypical SCID or other IEI not detected on newborn screening may present with more limited infectious presentations and/or profound immune dysregulation. Early management to prevent/control infections and reduce inflammatory complications is important for optimal outcomes of definitive therapies. Hematopoietic stem cell transplant (HSCT) is curative for IL-2Rα, IL-2Rβ, and IL-2Rγ defects, but gene therapy may yield comparable results for X-SCID. Defects in IL-2R subunits present with infectious and inflammatory phenotypes that should raise clinician's concern for IEI. Immunophenotyping may support the suspicion for diagnosis, but ultimately genetic studies will confirm the diagnosis and enable family counseling. Management of infectious and inflammatory complications will determine the success of gene therapy or HSCT.
AbstractList The current review highlights how inborn errors of immunity (IEI) due to IL-2 receptor (IL-2R) subunit defects may result in children presenting with a wide variety of infectious and inflammatory presentations beyond typical X-linked severe combined immune deficiency (X-SCID) associated with IL-2Rγ. Newborn screening has made diagnosis of typical SCID presenting with severe infections less common. Instead, infants are typically diagnosed in the first days of life when they appear healthy. Although earlier diagnosis has improved clinical outcomes for X-SCID, atypical SCID or other IEI not detected on newborn screening may present with more limited infectious presentations and/or profound immune dysregulation. Early management to prevent/control infections and reduce inflammatory complications is important for optimal outcomes of definitive therapies. Hematopoietic stem cell transplant (HSCT) is curative for IL-2Rα, IL-2Rβ, and IL-2Rγ defects, but gene therapy may yield comparable results for X-SCID. Defects in IL-2R subunits present with infectious and inflammatory phenotypes that should raise clinician's concern for IEI. Immunophenotyping may support the suspicion for diagnosis, but ultimately genetic studies will confirm the diagnosis and enable family counseling. Management of infectious and inflammatory complications will determine the success of gene therapy or HSCT.
Author Hernandez, Joseph D
Hsieh, Elena W Y
Author_xml – sequence: 1
  givenname: Joseph D
  surname: Hernandez
  fullname: Hernandez, Joseph D
  organization: Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, School of Medicine, Stanford University, Lucile Packard Children's Hospital, Palo Alto, California
– sequence: 2
  givenname: Elena W Y
  surname: Hsieh
  fullname: Hsieh, Elena W Y
  organization: University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA
BackLink https://www.ncbi.nlm.nih.gov/pubmed/36165614$$D View this record in MEDLINE/PubMed
BookMark eNpNj8tKAzEYhYMo9qJvIJIXmDZ_MpNJ3JXipTClIgruSi7_2BHnQpJZ-PZaVPBszuL7OHBm5LTrOyTkCtgCmC6X293jgv0LgIITMoVCQCa1ep2QWYzv30BAoc_JREiQhYR8Sp5W9C2gSdQ3MY3Bms4hbTqaDkjrPji8oZsq4zSgwyH1gXqs0aV49MM4JNq07dghPfQt9jGZ2MQLclabj4iXvz0nL3e3z-uHrNrdb9arKnNC8pRZpZCXLC81shylZrlWErFUzAIyLLiqpRU5U0Z6XnpvvDQenDhia3TN5-T6Z3cYbYt-P4SmNeFz_3eOfwEki1I3
CitedBy_id crossref_primary_10_3390_ijms24076468
crossref_primary_10_3389_fimmu_2023_1279201
crossref_primary_10_1016_j_clim_2024_110288
ContentType Journal Article
Copyright Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Copyright_xml – notice: Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
DBID CGR
CUY
CVF
ECM
EIF
NPM
DOI 10.1097/MOP.0000000000001181
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
DatabaseTitleList MEDLINE
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod no_fulltext_linktorsrc
Discipline Medicine
EISSN 1531-698X
ExternalDocumentID 36165614
Genre Review
Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural
GrantInformation_xml – fundername: NIAMS NIH HHS
  grantid: K23 AR070897
GroupedDBID ---
.-D
.XZ
.Z2
01Q
0R~
4Q1
4Q2
4Q3
5GY
5RE
5VS
6PF
71W
8L-
AAAAV
AAHPQ
AAIQE
AAJCS
AAMTA
AARTV
AASCR
AAWTL
AAYEP
ABASU
ABBUW
ABDIG
ABJNI
ABOCM
ABPPZ
ABVCZ
ABXVJ
ABZAD
ACDDN
ACEWG
ACGFO
ACGFS
ACILI
ACWDW
ACWRI
ACXJB
ACXNZ
ADGGA
ADHPY
AE6
AEBDS
AENEX
AFDTB
AFEXH
AFMFG
AHQNM
AHVBC
AINUH
AJIOK
AJNWD
AJZMW
ALMA_UNASSIGNED_HOLDINGS
ALMTX
AMJPA
AMKUR
AMNEI
AOHHW
AWKKM
BQLVK
C45
CGR
CS3
CUY
CVF
DIWNM
DU5
E.X
EBS
ECM
EEVPB
EIF
EX3
F5P
FCALG
FL-
GNXGY
GQDEL
H0~
HLJTE
HZ~
IKREB
IN~
IPNFZ
JF7
JK3
JK8
K8S
KD2
L-C
LEELO
N9A
NPM
O9-
OAG
OAH
ODA
ODMTH
OHYEH
OJAPA
OLC
OLG
OLW
OPUJH
OVD
OVDKG
OVDNE
OVKID
OWU
OWV
OWW
OWX
OWY
OWZ
OXXIT
P2P
RIG
RLZ
S4R
S4S
TEORI
TSPGW
V2I
VVN
W3M
WOQ
WOW
X3V
X3W
XXN
XYM
YFH
YOC
ZFV
ID FETCH-LOGICAL-c362t-b88e270479e04e6904986ee780b1e0e528f6b3408a6d27ddad6ad1c30b1eba9f2
IngestDate Sat Sep 28 08:16:43 EDT 2024
IsPeerReviewed true
IsScholarly true
Issue 6
Language English
License Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
LinkModel OpenURL
MergedId FETCHMERGED-LOGICAL-c362t-b88e270479e04e6904986ee780b1e0e528f6b3408a6d27ddad6ad1c30b1eba9f2
PMID 36165614
ParticipantIDs pubmed_primary_36165614
PublicationCentury 2000
PublicationDate 2022-12-01
PublicationDateYYYYMMDD 2022-12-01
PublicationDate_xml – month: 12
  year: 2022
  text: 2022-12-01
  day: 01
PublicationDecade 2020
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle Current opinion in pediatrics
PublicationTitleAlternate Curr Opin Pediatr
PublicationYear 2022
SSID ssj0003159
Score 2.4094386
SecondaryResourceType review_article
Snippet The current review highlights how inborn errors of immunity (IEI) due to IL-2 receptor (IL-2R) subunit defects may result in children presenting with a wide...
SourceID pubmed
SourceType Index Database
StartPage 580
SubjectTerms Homeostasis
Humans
Infant, Newborn
Interleukin-2 Receptor alpha Subunit
Receptors, Interleukin-2 - genetics
Severe Combined Immunodeficiency - genetics
Severe Combined Immunodeficiency - therapy
X-Linked Combined Immunodeficiency Diseases
Title A great disturbance in the force: IL-2 receptor defects disrupt immune homeostasis
URI https://www.ncbi.nlm.nih.gov/pubmed/36165614
Volume 34
hasFullText
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LT-MwELYWVqq4IFh2l7d82FsUSPOwHW4VAhVEASEQvVVxPIEcSCNaLvx6xo-0EYUVuz1EVZxEkb-v02_seRDyB3giixCEj3YgRwdFBX4aRJmfFQWLVSI4mN3zwSXr38Xnw2Q4D2I32SVTeZC_fphX8j-o4jnEVWfJ_gOys4fiCfyO-OIREcbjlzDueQ_Gw1eI1cuzNNH_Lm4RtWhu0s7PLvzQQ7MGNXrXngIbvoF3PL_UU6_U6SHgPY6fYIw6cVJO2mq1Kd6kk6pcTGTdtPaYafF-eyXabijMw4j7kxIebfgYVJl378y9W2YIw1bIBjSmseuz1DQCntlOtxBZLhjCxPZnWjDQtvDv4OraFo50H5392r4cp6d-MqBFTJcHsnmmfx99Vza7GVoiS1xoA3ipl3HcX3SEIq7Jo0z54Uevs0I6zSPeeRxGedyukVXnMtCexX-dfIPqB-kMXFDEBrnpUUMD2qIBLSuKNKCGBkdUk4A2JKCOBNSRgFoS0BYJfpK705Pb477vWmX4OSqQqS-FgJDrdgEQxMBS9PsEA-AikF0IIAlFwWQUByJjKuRKZYplqptHelhmaRH-IsvVuIJNQrkMZMr1dnDB47jIJApMvDnO8fIEknyL_LazMaptPZRRM0_bn47skJU5p3bJ9wJ_gLCHam4q9w0yb5xWR9c
link.rule.ids 783
linkProvider National Library of Medicine
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+great+disturbance+in+the+force%3A+IL-2+receptor+defects+disrupt+immune+homeostasis&rft.jtitle=Current+opinion+in+pediatrics&rft.au=Hernandez%2C+Joseph+D&rft.au=Hsieh%2C+Elena+W+Y&rft.date=2022-12-01&rft.eissn=1531-698X&rft.volume=34&rft.issue=6&rft.spage=580&rft_id=info:doi/10.1097%2FMOP.0000000000001181&rft_id=info%3Apmid%2F36165614&rft_id=info%3Apmid%2F36165614&rft.externalDocID=36165614