New Blood Test Detects Local Immune Activity Without Painful Biopsies and Expensive Imaging

The method developed by scientists, led by Hebrew University of Jerusalem (HU; Jerusalem, Israel), could help patients avoid follow-ups with invasive measures, such as biopsies and expensive and potentially harmful imaging modalities such as PET/CT scans and MRIs.

The human immune system works hard to keep the body healthy and protect it against bacteria, viruses, fungi, parasites and cancerous cells. When the immune system is weakened, a person is at a risk for illnesses and dangerous infections; when it is overactive, a person is at a risk for inflammation and autoimmune diseases. Therefore, accurate monitoring of immune system activity is vital to health.

Currently, the main way to test the immune system’s health is a blood test that counts immune (white blood) cells in the body. If the number comes out higher than normal, it may mean there’s an infection in the body that the immune system is fighting off. However, these blood tests often fail to catch immune system activity in the body’s remote tissues, such as those found in bone marrow, lymph nodes and other organs. In those cases, patients must follow-up with invasive measures, such as biopsies and expensive and potentially harmful imaging modalities such as PET/CT scans and MRI’s. And even then, such advanced testing doesn’t always detect the problem.

The new method to monitor remote immune processes relies on two fundamental biological principles. First, dying cells release fragments of DNA into the blood stream. Second, the DNA of each cell type contains a unique chemical pattern called methylation. Based on these principles, scientists can identify from which tissue the circulating fragments of DNA originated and infer disease states. For example, if a patient is battling breast cancer, there will be an elevation of DNA fragments (which is deposited into the blood stream after a cell dies) originating from breast cells and carrying the methylation hallmarks of breast cells, ditto for cardiac DNA fragments during heart attacks.

As part of their work, the researchers identified the specific DNA methylation patterns among immune and inflammatory cells types. This helped them detect DNA fragments that were deposited into the blood stream when those immune cells died. The researchers tested their theory and found proof of concept by testing several medical conditions where the immune system is activated but standard blood cell counts are normal. The first was with eosinophilic esophagitis (EoE), a chronic allergic disease that affects kids and adults and is often difficult to diagnose. To date, EoE diagnoses require invasive endoscopic biopsies because most patients’ blood counts come back normal. However, probing further, the team found that EoE patients’ blood contains abnormally high levels of DNA fragments from eosinophils (as identified by their unique DNA methylation pattern).

The team found similar success with lymphoma, a type of cancer that usually doesn’t show up in blood tests. However, the new blood test does pick up DNA fragments left by the immune system’s fight with lymphoma, without the need for bone marrow aspiration and further imaging. Currently, the team is conducting a study of people who’ve been vaccinated against COVID-19 to see whether the levels of DNA released from antibody-producing B-cells increased after they received the vaccine.

“Our research suggests that, in principle, doctors could monitor remote but critical immune processes by measuring the immune battle’s casualties, that is, immune-derived DNA fragments circulating in patients’ blood,” said MD/PhD student Ilana Fox-Fisher at HU’s Institute for Medical Research-Israel Canada (IMRIC). ”Our new non-invasive blood test could go a long way in helping diagnosis and monitoring this disease.”

“We’re hopeful this new blood test will give clinicians a more accurate picture of the state of their patient’s health, beyond the standard blood counts which often do not tell the whole story and frequently necessitate invasive follow-up tests and biopsies,” added Fox-Fisher.

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Hebrew University of Jerusalem