Highlights
- •Genomic biomarkers used as a diagnostic tool in sarcoidosis and CBD.
- •CD55, TNFα, and CXCL9 gene levels distinguish between sarcoidosis and CBD.
- •CD55 and TNFα gene levels distinguish between sarcoidosis and controls.
Abstract
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.
Keywords
Abbreviations:
AUC (Area under the curve), BeLPT (Beryllium lymphocyte proliferation test), BeS (Beryllium sensitization), BAL (Bronchoalveolar lavage), CBD (Chronic beryllium disease), DLCO (Diffusing capacity for carbon monoxide), FEV1 (Forced expiratory volume in 1 s), FVC (Forced vital capacity), ROC (Receiver operating characteristic)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: April 05, 2021
Accepted:
March 30,
2021
Received in revised form:
March 29,
2021
Received:
September 3,
2020
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
