Molecules in Blood Cells ID’d as Potential MG Diagnosis Biomarkers

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Two molecules in blood cells may be potential biomarkers for diagnosing myasthenia gravis (MG), a study suggests.

Researchers found levels to be lower in mononuclear cells — a mixture of different cell types that circulate in the bloodstream and have a round nucleus — of patients with MG than in those of healthy individuals.

“They can distinguish MG patients from healthy controls with high accuracy,” the researchers wrote.

The study, “DCAF12 and HSPA1A may serve as potential diagnostic biomarkers for myasthenia gravis,” was published in BioMed Research International by a team of researchers in China.

MG is an autoimmune disease caused by certain self-reactive antibodies that impair the communication between nerve and muscle cells, resulting in muscle weakness.

A common way to diagnose MG is to look for these antibodies in the blood. However, tests come back negative for about 10% of patients with MG, underscoring the need for new disease blood biomarkers.

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“Early diagnosis of MG, along with a timely and effective treatment plan, will result in a better prognosis,” the researchers wrote.

As in many other autoimmune diseases, immune cells can play a part in how MG develops by prompting the body to make more self-reactive antibodies. They also can release cytokines — molecules that signal other immune cells to get involved in mounting an immune response.

Researchers looked for differences in immune cells between patients with MG and healthy people, and whether they have a molecular signature that could help in the disease’s diagnosis.

They analyzed and compared data from 13 blood samples from MG patients with 12 blood samples from healthy individuals. The data were available from a public database called GEO.

Researchers first looked for differences in gene activity levels. They found differences in the levels of 113 genes, with 76 being underactive and 37 being overly active in patients versus healthy individuals.

Next, researchers searched for differences in immune cells by looking at their signature molecules. They found differences in six types of immune cells, which were lower in blood samples from MG patients, but focused on one: the CD56bright natural killer cells.

A natural killer cell is a type of white blood cell that has has granules (small particles) with enzymes that can destroy other cells in the body. CD56bright natural killer cells help control a heightened immune response by destroying certain other cells of the immune system. They are called CD56bright because they are rich in CD56, a protein that sits on their surface.

Researchers think that in people with MG, fewer CD56bright natural killer cells may mean the immune response is not under control as well, which may contribute to the disease. However, “the detailed immune mechanism of [natural killer] cells in MG still requires further research,” they wrote.

Of the 113 genes initially identified, nine were involved in immune responses. Two of them, DCAF12 and HSPA1A, were significantly lower in blood samples from MG patients. Both provide instructions for making proteins involved in protein folding.

To confirm their findings, researchers isolated mononuclear cells from the blood of 10 MG patients and 10 healthy people. They found DCAF12 and HSPA1A activity levels were significantly lower in MG patients.

According to researchers, “low expression of DCAF12 and HSPA1A may increase MG development risk by affecting the number and function of CD56bright natural killer cells.”

While DCAF12 and HSPA1A were not compared in the study with other commonly used biomarkers, their diagnostic performance was considered to be good. Their sensitivity, or ability to correctly identify MG patients, was 90% and 80%.

“Detecting the levels of DCAF12 and HSPA1A … in suspected patients with MG in clinical practice can diagnose MG early and timely treatment measures can be performed,” the researchers wrote.

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Myasthenia Gravis News conducted a survey from Feb. 11-March 28 to gain greater insight into the characteristics of the MG community and disease management. Results of the survey have now been published. Click on the image to view the infographic, and click here to read the story.