Plasma microRNAs as Biomarkers in Hereditary Angioedema.
Biomarker
Disease severity
Hereditary Angioedema
MicroRNA
Phenotype
Journal
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology
ISSN: 1534-4436
Titre abrégé: Ann Allergy Asthma Immunol
Pays: United States
ID NLM: 9503580
Informations de publication
Date de publication:
25 Feb 2024
25 Feb 2024
Historique:
received:
12
10
2023
revised:
19
02
2024
accepted:
20
02
2024
medline:
28
2
2024
pubmed:
28
2
2024
entrez:
27
2
2024
Statut:
aheadofprint
Résumé
Hereditary angioedema (HAE) is an autosomal dominant disease with variable expression. In some families with identical genetic abnormality, the expression can range from several attacks per month to no attacks at all. It is hypothesized that post-transcriptional gene regulation account for the variable expression of the disease. We sought to identify candidate micro-ribonucleic acids (miRNAs) that could play a role in HAE by determining whether miRNAs differentially expressed in HAE vs. non-HAE subjects, and whether expression profiles tracked with severity. This study compared serum miRNA expression in HAE subjects to non-HAE subjects using RNAseq. Associations between miRNA expression and HAE severity was assessed in subjects with mild disease (<6 attacks a year) vs. severe disease (>1 attack per month). Functions of candidate miRNAs were analyzed using in silico methods. There were robust miRNA expression differences between HAE subjects and non-HAE controls. A cluster analysis identified sub-groups of HAE patients with unique miRNA profiles that tracked with frequency of attacks. Two miRNAs, miR-99b-5p and miR-127-3p were differentially expressed between mild and severe HAE (adjusted p-val <0.05). In silico analysis demonstrate a function of differentially expressed miRNAs in regulation of C1INH, kininogen, the bradykinin B2 receptor, and adherens junction function. Candidate microRNAs were identified that could distinguish subjects with and without HAE, and may be used to identify phenotypes of HAE.
Sections du résumé
BACKGROUND
BACKGROUND
Hereditary angioedema (HAE) is an autosomal dominant disease with variable expression. In some families with identical genetic abnormality, the expression can range from several attacks per month to no attacks at all. It is hypothesized that post-transcriptional gene regulation account for the variable expression of the disease.
OBJECTIVE
OBJECTIVE
We sought to identify candidate micro-ribonucleic acids (miRNAs) that could play a role in HAE by determining whether miRNAs differentially expressed in HAE vs. non-HAE subjects, and whether expression profiles tracked with severity.
METHODS
METHODS
This study compared serum miRNA expression in HAE subjects to non-HAE subjects using RNAseq. Associations between miRNA expression and HAE severity was assessed in subjects with mild disease (<6 attacks a year) vs. severe disease (>1 attack per month). Functions of candidate miRNAs were analyzed using in silico methods.
RESULTS
RESULTS
There were robust miRNA expression differences between HAE subjects and non-HAE controls. A cluster analysis identified sub-groups of HAE patients with unique miRNA profiles that tracked with frequency of attacks. Two miRNAs, miR-99b-5p and miR-127-3p were differentially expressed between mild and severe HAE (adjusted p-val <0.05). In silico analysis demonstrate a function of differentially expressed miRNAs in regulation of C1INH, kininogen, the bradykinin B2 receptor, and adherens junction function.
CONCLUSION
CONCLUSIONS
Candidate microRNAs were identified that could distinguish subjects with and without HAE, and may be used to identify phenotypes of HAE.
Identifiants
pubmed: 38412917
pii: S1081-1206(24)00105-4
doi: 10.1016/j.anai.2024.02.017
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of competing interest *Dr Craig: CSL Behring (research, speaker, consultant), Biocryst (research, consultant), Ionis (research), Kalvista (research, consultant), Pharvaris (research), Takeda (research, speakers, consultant), Grifols (speaker, consultant), BioMarin (researcher, consultant), Spark (consultant), Ionis (researcher, consultant), Intellia (research).No other authors have a conflict of interest