Restoring Function of Immune Cell Type May Aid in gMG Remission
Generalized myasthenia gravis (gMG) may be associated with a deficiency in a type of immune cell called myeloid-derived suppressor cells (MDSCs), a study suggests, and that restoring their function and increasing their numbers may help reduce symptoms.
Treatment with immunosuppressants resulted in an expansion of MDSCs, which was linked to a reduction in certain subsets of immune T helper (Th) cells previously implicated in the abnormal immune responses that drive MG.
The study, “Increased Frequency of Myeloid-Derived Suppressor Cells in Myasthenia Gravis After Immunotherapy,” was published in the journal Frontiers in Neurology.
In myasthenia gravis (MG), the immune system produces antibodies that mistakenly attack proteins involved in nerve-muscle communication, leading to symptoms of muscle weakness and fatigue.
These abnormal immune responses are mediated by antibody-producing B-cells and also rely on certain Th cells — a type of immune cell that activates other immune cells.
Similar to other autoimmune diseases, MG is associated with a reduced number and/or function of immunosuppressive immune cells, such as regulatory T-cells (Tregs) and B-cells (Bregs), which work by dampening immune responses, thereby helping to prevent autoimmunity.
While MDSCs are known to also have immunosuppressive and anti-inflammatory effects, their role in autoimmune diseases remains unclear due to contradictory results from different studies.
Now, a team of researchers in China provided evidence that MDSCs’ ability to block immune responses is also impaired in MG and that restoring such function may help relieve disease symptoms.
They analyzed MDSCs’ frequency and function in blood samples taken from 30 adults (16 women and 14 men) with gMG before and after immunosuppressive treatment, as well as from 30 healthy adults (13 women and 17 men). All participants were recruited at a single center from 2019 to 2020.
Participants diagnosed with the disease had a mean age of 49.1 years, had lived with the disease for a mean of 15.2 months (little over a year), and were positive for antibodies against the acetylcholine receptor — the most common type of MG-causing antibody.
They had no other autoimmune disease and had not received prior immunotherapy. They were followed for six to 12 months after corticosteroid treatment with or without other immunosuppressive treatments.
Results showed that gMG patients experienced a significant reduction in symptom severity after treatment, as assessed with the Myasthenia Gravis Activities of Daily Living scale and the Quantitative Myasthenia Gravis score.
While MDSCs’ frequency was similar between healthy controls and untreated patients, it was significantly increased in patients after immunosuppressive treatment.
This rise in MDSCs was significantly associated with a reduction in the frequencies of Th1 and Th17 cells — two pro-inflammatory immune cell subsets previously shown to contribute to the development and severity of MG. No links between MDSC frequency and those of Tregs and Bregs were detected.
In addition, the team found evidence that MDSCs from untreated patients showed an impaired ability to suppress T-cell-derived production of interferon gamma, a pro-inflammatory molecule.
This immunosuppressive function was improved in patients after immunotherapy, and associated with a significant increase in the activity of genes coding for molecules implicated in MDSC-mediated immunosuppression.
One of these molecules, Arg-1, was previously found to suppress T-cell growth and their production of pro-inflammatory molecules. However, other lab-dish studies using MDSCs from people with another autoimmune disease suggested an opposite role.
These findings suggest that MDSCs’ immunosuppressive function is impaired in gMG patients and that it can be improved after immunotherapy, further supporting a role for these cells in disease remission.
Larger studies with a longer follow-up are needed to confirm these findings and clarify the role of MDSC-derived Arg-1 in T-cell suppression in MG.
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