High Blood Sugar Levels Prompt MG-driving Immune Cell Activity: Study
MG patients with diabetes had higher levels of cTfh cells than those without diabetes
The high blood sugar levels that characterize diabetes may prompt immune cells to be activated that can drive and worsen myasthenia gravis (MG), a recent study suggests.
These findings indicate that tightly controlling blood sugar levels may benefit MG patients who also have diabetes.
The study, “Diabetes mellitus aggravates humoral immune response in myasthenia gravis by promoting differentiation and activation of circulating Tfh cells,” was published in Clinical Immunology.
In MG, an autoimmune attack interferes with the communication between nerve and muscle cells, causing muscle weakness and other symptoms. This attack is driven by immune proteins called antibodies, which are produced by a type of immune cell called B-cells. The most common type of MG-driving antibody targets the acetylcholine receptor (AChR).
Diabetes mellitus is a metabolic disorder that causes glucose, or blood sugar, levels to become excessively high. Studies have suggested diabetes can alter the activity of the immune system, but its implications in autoimmune diseases such as MG are poorly understood.
Researchers in China analyzed blood samples from 28 people with MG — 15 with diabetes, 13 without — to explore the possible connection between diabetes and MG. Both groups were similar in age and gender distribution.
Researchers first looked at the levels of circulating follicular helper T-cells (cTfh cells), a type of immune cells that help B-cells become active and produce antibodies.
Results showed MG patients with diabetes had higher levels of cTfh cells compared with those who didn’t. MG patients with diabetes also had more cTfh cells producing activation markers, such as the protein ICOS.
“In the current study, we found a higher population of cTfh cells in MG patients with [diabetes mellitus],” the researchers wrote. “We further analyzed the activation markers of cTfh cells and found increased ICOS expression in cTfh cells of MG patients with [diabetes mellitus].”
Scientists next examined B-cell levels. While most B-cell populations were similar in MG patients with or without diabetes, those with diabetes had significantly higher levels of plasmablasts, B-cells that have been primed toward antibody production, results showed.
There was a significant correlation between levels of ICOS-expressing cTfh cells and plasmablast levels, statistical analyses showed.
Researchers also showed in experiments in cell models that high glucose levels, as seen in diabetes, can promote cTfh cell activation, as shown by an increased production of ICOS. These activated cTfh cells promoted B-cells to become plasmablasts and produce antibodies. This glucose-driven cTfh cell activation was dependent on the activity of a biochemical pathway called mTOR, results showed.
“The present results showed diabetes mellitus promoted cTfh cells differentiation and activation in MG patients, which positively correlated with increased plasmablasts in the blood,” the researchers wrote, adding diabetes and high glucose appear to promote the generation of AChR-antibody secreting cells that drive MG. They said “tight glycemic control” may benefit MG patients with diabetes mellitus.”