Diabetes May Be Immune System Trigger in MG, Worsening Symptoms
Diabetes, which causes blood sugar levels to rise abnormally, may trigger a stronger immune response and worsen myasthenia gravis (MG) symptoms, a study in a rat disease model suggests.
If its findings hold true in people, they could provide evidence of the importance of blood sugar control in easing MG symptoms, the study’s scientists noted.
The study, “Diabetes mellitus exacerbates experimental autoimmune myasthenia gravis via modulating both adaptive and innate immunity,” was published in the Journal of Neuroinflammation.
Diabetes, also known by its full name as diabetes mellitus, occurs when the body fails to respond to or does not produce enough insulin, a hormone in the pancreas that allows cells to take up and use sugar. It is common among people with MG, particularly those with late-onset disease.
Its impact on the development of MG, however, is largely unknown. Now, a team of scientists in China found that diabetes may have “overlapping roles” with MG, by amplifying the immune response that takes place in this disease.
Researchers performed experiments on 15 female rats with experimental autoimmune MG (EAMG), a model that mimics many aspects of the human disease. It can be induced by making animals produce antibodies against the acetylcholine receptor (AChR), which attack this protein receptor on muscle cells, resulting in muscle weakness.
They also induced hyperglycemia (high sugar levels) in eight of the rats by injecting them with streptozotocin, a molecule that is toxic to the insulin-producing cells of the pancreas. These rats were considered to have diabetes. The remaining seven animals were injected with a buffer solution and served as controls.
Researchers then watched for changes in MG clinical scores, which were determined based on muscle strength, motor activity, and posture.
Clinical scores were worse — with symptoms being more severe and manifesting sooner — in rats with diabetes than in controls, the team found, and this worsening was due to higher levels of anti-AChR antibodies and greater numbers of antibody-producing cells.
Rats with diabetes also had greater numbers of memory B-cells — a type of immune cell that remembers potential invaders — and follicular helper T-cells — another type of immune cell, found in the spleen and lymph nodes, that helps in antibody production. These two types of cells are part of the adaptive immune system, which provides highly specialized protection against certain threats.
When researchers removed immune cells from animals’ spleens to discover what could be driving these changes, they found it to be advanced glycation end products (AGEs), which are proteins or fatty molecules that become altered — and harmful — after being exposed to sugars.
Inflammation plays a role in MG, and the numbers of a particular type of helper T-cell, which makes a pro-inflammatory molecule called interferon gamma, were higher in rats with diabetes than in controls. In turn, levels of regulatory T-cells, which fine-tune the body’s immune response by suppressing it, were lower.
Researchers also watched for changes in the spleen and lymph nodes. They found that the spleen was smaller in rats with diabetes than in controls.
To check if cells of the innate immune system, which provides a non-specific first line of protection, could also be involved, the researchers looked at natural killer (NK) cells. These cells can “serve as a bridge between innate and adaptive immunity,” they noted.
Although the numbers of NK cells were not greater in rats with diabetes, these cells had more CXCR5 on their surface. CXCR5 is a protein that helps B-cells migrate to the spleen, where they are able to make antibodies.
“Diabetes promoted both adaptive and innate immunity and exacerbated clinical symptoms in EAMG,” the researchers wrote, adding that further research is needed to confirm that lowering blood sugar or AGE levels might help in treating MG.
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