The objective of future personalized medicine is the early detection of a disease in its preclinical stage when the patient is still healthy. In order to achieve this, a more thorough understanding as to the changes in cell metabolism within the relevant organ in the early stages of the disease needs to be gained. Moreover, it should be possible to obtain evidence of such changes in easily accessible diagnostic material. Not until this step is taken will large-scale diagnostics or also long-term monitoring of individual patients be possible.
In a recently published study in the scientific journal EMBO Molecular Medicine (Mayr et al., 2021), DZL scientists have provided proof of concept that, by means of systemic analyses of bodily fluids (body fluid proteomic), conclusions about the metabolic behaviour of single cells (single-cell transcriptomic) are possible. For instance, specific changes in gene expression, i.e. in the reading frame of genetic material, have been identified by means of protein analysis of the material obtained from bronchoalveolar lavage (BAL), so early changes in patients with pulmonary fibrosis could be derived. With the help of machine learning, it could be demonstrated that protein signatures in lung fluids correlate with lung function in a large patient cohort suffering from pulmonary fibrosis. They were consistent with the specific state of the cell and the change in cell frequency with disease progression. The study in particular identified an activated state of what is referred to as pericytes, a specific type of cell that can be found on the walls of thin blood vessels. This cell state correlated with disease severity and was reflected by the quantity of CFHR1 protein (complement factor H-related protein 1) in BAL. Furthermore, the authors found that, in pulmonary fibrosis, the de-differentiation of epithelial cells (alveolar type II) was reflected in the level of CFTAC1 protein. This level was detected in both BAL and – much less invasively obtainable - blood plasma. Hence, this protein is a good candidate for a novel peripheral biomarker for the health of bronchoalveolar epithelium.
With this study, the authors have created an integrated single-cell atlas of human lung fibrosis for the first time and provided evidence of the correlation of a number of peripheral protein biomarker signatures with cellular changes in the lungs. Evidence of the clinical benefit of these novel biomarker signatures for monitoring the development of the disease now needs to be provided in prospective longitudinal studies. Conceptually, this study provides important evidence for the concept of non-invasive monitoring of cell state in future individualized medicine.
https://www.embopress.org/doi/epdf/10.15252/emmm.202012871
