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Mar 22
New blood test may detect multiple diseases
Scientists have developed a new blood test that may detect multiple diseases, including diabetes, cancer, traumatic injury and neuro degeneration, in a highly sensitive and specific manner.

The novel method, developed in a series of experiments involving 320 patients and controls, infers cell death in specific tissue from the methylation patterns of circulating DNA that is released by dying cells.

Cell death is a central feature of human biology in health and disease, according to researchers led by Ruth Shemer and Yuval Dor from The Hebrew University of Jerusalem, and Benjamin Glaser from Hadassah Medical Centre.

It can signify the early stages of pathology (eg a developing tumour or the beginning of an autoimmune or neurodegenerative disease), mark disease progression, reflect the success of therapy (eg anti cancer drugs), identify unintended toxic effects of treatment and more.

However to date, it is not possible to measure cell death in specific human tissues non-invasively.

The new blood test detects cell death in specific tissues by combining two important biological principles. First, dying cells release fragmented DNA to the circulation, where it travels for a short time.

The second principle is that the DNA of each cell type carries a unique chemical modification called methylation.

Methylation patterns of DNA account for the identity of cells (the genes that they express), are similar among different cells of the same type and among individuals, and are stable in healthy and disease conditions.

For example, the DNA methylation pattern of pancreatic cells differs from the pattern of all other cell types in the body.

The researchers have identified multiple DNA sequences that are methylated in a tissue-specific manner (for example, unmethylated in DNA of neurons and methylated elsewhere), and can serve as biomarkers for the detection of DNA derived from each tissue.

They then developed a method to detect these methylated patterns in DNA circulating in blood, and demonstrated its utility for identifying the origins of circulating DNA in different human pathologies, as an indication of cell death in specific tissues.

They were able to detect evidence for pancreatic beta-cell death in the blood of patients with new-onset type 1 diabetes, oligodendrocyte death in patients with relapsing multiple sclerosis, brain cell death in patients after traumatic or ischemic brain damage, and exocrine pancreas cell death in patients with pancreatic cancer or pancreatitis.

"Our work demonstrates that the tissue origins of circulating DNA can be measured in humans. This represents a new method for sensitive detection of cell death in specific tissues, and an exciting approach for diagnostic medicine," said Shemer.

The findings were published in the journal PNAS.

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