Immunologic and Genetic Contributors to CD46-Dependent Immune Dysregulation.
CD46
Inborn errors of immunity
SLE
aHUS
atypical hemolytic uremic syndrome
haploinsufficiency
next-generation sequencing
penetrance
primary immunodeficiency complement
systemic lupus erythematosus
Journal
Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
received:
27
10
2022
accepted:
30
06
2023
medline:
21
11
2023
pubmed:
21
7
2023
entrez:
21
7
2023
Statut:
ppublish
Résumé
Mutations in CD46 predispose to atypical hemolytic uremic syndrome (aHUS) with low penetrance. Factors driving immune-dysregulatory disease in individual mutation carriers have remained ill-understood. In addition to its role as a negative regulator of the complement system, CD46 modifies T cell-intrinsic metabolic adaptation and cytokine production. Comparative immunologic analysis of diseased vs. healthy CD46 mutation carriers has not been performed in detail yet. In this study, we comprehensively analyzed clinical, molecular, immune-phenotypic, cytokine secretion, immune-metabolic, and genetic profiles in healthy vs. diseased individuals carrying a rare, heterozygous CD46 mutation identified within a large single family. Five out of six studied individuals carried a CD46 gene splice-site mutation causing an in-frame deletion of 21 base pairs. One child suffered from aHUS and his paternal uncle manifested with adult-onset systemic lupus erythematosus (SLE). Three mutation carriers had no clinical evidence of CD46-related disease to date. CD4
Identifiants
pubmed: 37477760
doi: 10.1007/s10875-023-01547-y
pii: 10.1007/s10875-023-01547-y
pmc: PMC10661731
doi:
Substances chimiques
Cytokines
0
CD46 protein, human
0
Membrane Cofactor Protein
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1840-1856Subventions
Organisme : Intramural NIH HHS
ID : ZIA HL006223
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
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