Genomic biomarkers in chronic beryllium disease and sarcoidosis

Respir Med. 2021 Oct:187:106390. doi: 10.1016/j.rmed.2021.106390. Epub 2021 Apr 5.


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: Chronic beryllium disease; Gene expression; Genomic biomarkers; Granulomatous lung disease; Sarcoidosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Berylliosis / diagnosis*
  • Berylliosis / genetics*
  • Biomarkers / metabolism
  • CD55 Antigens / genetics
  • CD55 Antigens / metabolism
  • Chemokine CXCL9 / genetics
  • Chemokine CXCL9 / metabolism
  • Chronic Disease
  • Diagnosis, Differential
  • Eosinophil Cationic Protein / genetics
  • Eosinophil Cationic Protein / metabolism
  • Female
  • Gene Expression / genetics*
  • Gene Expression Regulation / genetics*
  • Genetic Markers
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Male
  • Middle Aged
  • Sarcoidosis, Pulmonary / diagnosis*
  • Sarcoidosis, Pulmonary / genetics*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Biomarkers
  • CD55 Antigens
  • CXCL9 protein, human
  • Chemokine CXCL9
  • Genetic Markers
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Eosinophil Cationic Protein