Sarcoidosis Phenotypic Traits Linked to Novel Bronchoalveolar Lavage Cell Gene Expression

sarcoidosis lungs
sarcoidosis lungs
Researchers looked for specific BAL cell gene expression patterns indicative of distinct disease phenotypic traits.

Specific gene profiles of bronchoalveolar lavage (BAL) cells are associated with phenotypic manifestations of sarcoidosis such as activity and disease severity, including immune, inflammatory, and profibrotic mediators as identified via genome-wide transcriptome analysis, according to results published in the European Respiratory Journal. Study results also suggest 4 possible sarcoidosis endotypes with specific molecular, clinical, and environmental traits.

A team of investigators for the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study conducted a supervised and unsupervised analysis to highlight BAL cell gene signatures that may be linked to phenotypic sarcoidosis.

A total of 215 patients with pulmonary sarcoidosis were enrolled in the study and ribonucleic acid (RNA) sequencing was performed on BAL cells obtained from the cohort; 209 BAL samples were included from 8 predefined clinical groups.

In the supervised analysis, which was conducted to identify known associations between predefined parameters, there was an association between distinct transcriptional programs and major pulmonary phenotypic manifestations of sarcoidosis.

Such manifestations included T helper (Th)1 and Th17 pathways linked to hilar lymphadenopathy, transforming growth factor-β1 (TGFB1) and mammalian target of rapamycin (mTOR) signaling with parenchymal involvement, and interleukin (IL)-7 and IL-2 with airway involvement.

In an unsupervised analysis, which was conducted to identify novel relationships using weighted gene coexpression network analysis, the authors highlighted gene modules that identified 4 possible sarcoidosis endotypes. These included hilar lymphadenopathy with increased acute T-cell immune response, extraocular organ involvement with PI3K activation pathways, and multiorgan with increased IL-1 and IL-18 immune and inflammatory responses.

Gene expression, pulmonary function tests, and cell differentials from an independent microarray expression dataset of a sarcoidosis cohort were used to validate the presence of these endotypes. 

“[O]ur study identified gene profiles associated with major phenotypic manifestations of pulmonary involvement in sarcoidosis, as well as identified 4 novel endotypes that help to better stratify patients in the future,” the study authors noted.

“Our findings support the design of future studies to focused on specific attributes of sarcoidosis, and the use of novel single cell profiling technologies leading to novel therapeutic interventions and biomarkers,” they concluded.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of authors’ disclosures.


Vukmirovic M, Yan X, Gibson KF, et al for the GRADS Investigators. Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis. Eur Respir J. Published online June 3, 2021. doi:10.1183/13993003.02950-2020