Researchers have created a novel immune-profiling method that can return detailed immune cell type proportions by using only DNA from blood.
DNA methylation arrays
Flow cytometry is a powerful tool to count, sort or measure characteristics of cells. While it is commonly used in research and to diagnosis disorders, flow cytometry requires intact and usually fresh cells. These cells must be processed promptly to preserve cell integrity and surface markers that can identify immune cell types.
The developments in DNA methylation microarrays have enabled researchers to gain a deeper understanding of DNA methylation and how it is affected by environmental exposures and during disease. One of the most common biological matrices for these investigations is peripheral blood. Blood DNA methylation profiles can provide information from multiple cell lineages and cell states. Every cell lineage has a unique DNA methylation pattern which regulates cell-specific gene expression.
The reference-based approach considers that the main source of signal variability in heterogenous samples, like the blood, reflects the signals’ proportions in the different cell components. In order to improve the utility of cell-type deconvolution, reference library improvements and expansions need to be made to include additional cell types and broaden the scope of DNA methylation-based immune phenotyping.
A novel immune-profiling method
In a recent paper, published in Nature Communications, researchers reported a novel immune-profiling method that is capable of reporting specific immune cell types using only DNA from blood rather than from fresh cell samples. This approach offers the opportunity for researchers to examine health and disease using the millions of stored blood samples from biobanks worldwide.
Currently, the complete cell blood count is used to diagnose patients in the clinic. This approach is limited to five immune cell types. In the new approach, the team expanded the reference-based deconvolution of blood DNA methylation to include 12 leukocyte subtypes. These included neutrophils, eosinophils, basophils, monocytes, naïve and memory B cells, naïve and memory CD4 + and CD8 + T cells, natural killer, and T regulatory cells.
Lead author, Lucas A. Salas, said:
“Not only does the approach return more than double the number of cell types compared with standard clinical methods, but because it doesn’t depend on surface markers or intact cells, it can be used with either fresh or archival blood.”
The team applied this approach to deconvolve cancer, ageing and autoimmune disease datasets. Here, they observed immune profile responses to chemotherapy and radiation therapy.
Corresponding author, Brock C. Christensen, said:
“Detailed immune profiling with our new method is expected to uncover biomarkers of response to existing and emerging cancer immunotherapies as well as to other immunomodulatory drugs.
This technology also has great potential in advancing cancer immunoprevention efforts.”
The team hope to next evaluate the range of uses for this tool that will most immediately benefit clinicians and patients.
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