Anti-thyroid Antibodies Tied to Specific Immune Profile in MG
Myasthenia gravis (MG) patients with antibodies against the thyroid gland have significantly more B-cells — the immune cells that produce antibodies — and fewer immune T-cells, a small single-center study in China shows.
These early findings suggest the presence of anti-thyroid antibodies may affect the success of immunomodulating therapies used in MG and that patients with these antibodies may benefit more from B-cell-suppressing therapies, the researchers noted.
Larger studies are needed to confirm these findings and assess the value of testing for anti-thyroid antibodies in MG patients to improve treatment decisions.
The study, “Differences in immunophenotypes between myasthenia gravis patients with and without thyroid antibodies,” was published in the journal Muscle & Nerve.
MG is an autoimmune disease in which the immune system wrongly produces self-reactive antibodies against proteins that play a key role in the function of the neuromuscular junction — the region where nerve-muscle communication takes place.
These antibodies most commonly attack the acetylcholine receptor (AChR), a cell surface protein, but many patients have antibodies against an enzyme called muscle-specific tyrosine kinase. These abnormal immune attacks are mostly driven by two types of immune cells: B-cells, which produce antibodies, and T-cells, which can regulate the activity of other immune cells.
Autoimmune thyroid diseases (ATDs), caused by the abnormal production of antibodies against the thyroid gland, are the most common simultaneous conditions in people with MG, and such antibodies are detected in about 20–30% of MG patients.
The presence of anti-thyroid antibodies has been associated with changes in immune cell subsets and worse outcomes in several diseases, but whether this is true for MG remains largely unclear. This type of information “may contribute to individualized treatment decisions” in MG, the researchers wrote.
With this in mind, a team of researchers at the Huazhong University of Science and Technology in China compared the immune cell profile, as well as other clinical and lab features, between MG patients with and without anti-thyroid antibodies.
A total of 48 adults with MG (27 women and 21 men) who were positive for antibodies against AchR were included in the retrospective study. All had been hospitalized at a single Chinese hospital from April 2017 to May 2021, and none had received prior immunotherapy or had autoimmune diseases other than ATDs.
Patients had an average age of 48.7 years and antibodies against the thyroid gland were detected in 15 (31.3%) patients. Most (66.7%) patients had generalized MG, while 16 (33.3%) had ocular MG.
Results showed that a significantly higher proportion of patients with anti-thyroid antibodies had ocular MG relative to those without such antibodies (53.3% vs. 24.2%). The team hypothesized this may be due to structural similarities between proteins in eye muscles and those in the thyroid, meaning that MG-associated antibodies also may bind to thyroid proteins, mounting attacks against them as well.
Patients positive for antibodies against the thyroid had significantly higher counts and proportions of B-cells and reduced proportions of T-cells, activated T-cells, and specific T-cell subsets, compared with those without such antibodies.
In the group of anti-thyroid-positive patients, generalized MG was associated with a deficiency in natural killer cells — cells that are part of the body’s first line of defense — relative to ocular MG.
Notably, while patients with anti-thyroid antibodies had significantly more B-cells, they showed reduced levels of antibodies against AChR.
These findings highlight that MG patients with antibodies against the thyroid gland were more likely to have ocular MG “and to have impaired T-cell immunity, higher B-cell generation, and decreased [anti-AchR antibody levels],” the researchers wrote.
Since the immune profiles of MG patients with and without these antibodies were significantly different, “their sensitivity to immunotherapy may be different,” the team wrote.
B-cell-targeted therapy “may be most appropriate” for MG patients with anti-thyroid antibodies, while approaches suppressing T-cell activation “may be more applicable for [anti-thyroid antibody] negative patients due to their relatively active T-cell immunity,” the researchers wrote.
Larger studies are needed to confirm these preliminary findings and to assess differences in responses to specific immunotherapies between patients with and without antibodies against the thyroid.
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