Genomic biomarkers in chronic beryllium disease and sarcoidosis.
Adult
Aged
Berylliosis
/ diagnosis
Biomarkers
/ metabolism
CD55 Antigens
/ genetics
Chemokine CXCL9
/ genetics
Chronic Disease
Diagnosis, Differential
Eosinophil Cationic Protein
/ genetics
Female
Gene Expression
/ genetics
Gene Expression Regulation
/ genetics
Genetic Markers
Humans
Interferon-gamma
/ genetics
Male
Middle Aged
Sarcoidosis, Pulmonary
/ diagnosis
Tumor Necrosis Factor-alpha
/ genetics
Chronic beryllium disease
Gene expression
Genomic biomarkers
Granulomatous lung disease
Sarcoidosis
Journal
Respiratory medicine
ISSN: 1532-3064
Titre abrégé: Respir Med
Pays: England
ID NLM: 8908438
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
03
09
2020
revised:
29
03
2021
accepted:
30
03
2021
pubmed:
17
8
2021
medline:
9
2
2022
entrez:
16
8
2021
Statut:
ppublish
Résumé
Background Previous gene expression studies have identified genes IFNγ, TNFα, RNase 3, CXCL9, and CD55 as potential biomarkers for sarcoidosis and/or chronic beryllium disease (CBD). We hypothesized that differential expression of these genes could function as diagnostic biomarkers for sarcoidosis and CBD, and prognostic biomarkers for sarcoidosis. Study Design/Methods We performed RT-qPCR on whole blood samples from CBD (n = 132), beryllium sensitized (BeS) (n = 109), and sarcoidosis (n = 99) cases and non-diseased controls (n = 97) to determine differential expression of target genes. We then performed logistic regression modeling and generated ROC curves to determine which genes could most accurately differentiate: 1) CBD versus sarcoidosis 2) CBD versus BeS 3) sarcoidosis versus controls 4) non-progressive versus progressive sarcoidosis. Results CD55 and TNFα were significantly upregulated, while CXCL9 was significantly downregulated in CBD compared to sarcoidosis (p < 0.05). The ROC curve from the logistic regression model demonstrated high discriminatory ability of the combination of CD55, TNFα, and CXCL9 to distinguish between CBD and sarcoidosis with an AUC of 0.98. CD55 and TNFα were significantly downregulated in sarcoidosis compared to controls (p < 0.05). The ROC curve from the model showed a reasonable discriminatory ability of CD55 and TNFα to distinguish between sarcoidosis and controls with an AUC of 0.86. There was no combination of genes that could accurately differentiate between CBD and BeS or sarcoidosis phenotypes. Interpretation CD55, TNFα and CXCL9 expression levels can accurately differentiate between CBD and sarcoidosis, while CD55 and TNFα expression levels can accurately differentiate sarcoidosis and controls.
Identifiants
pubmed: 34399367
pii: S0954-6111(21)00096-2
doi: 10.1016/j.rmed.2021.106390
pmc: PMC8490480
mid: NIHMS1690894
pii:
doi:
Substances chimiques
Biomarkers
0
CD55 Antigens
0
CXCL9 protein, human
0
Chemokine CXCL9
0
Genetic Markers
0
Tumor Necrosis Factor-alpha
0
Interferon-gamma
82115-62-6
Eosinophil Cationic Protein
EC 3.1.27.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
106390Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL140357
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL114587
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES023826
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES025722
Pays : United States
Organisme : NIEHS NIH HHS
ID : K01 ES020857
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
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