High levels of anti-AChR antibodies tied to greater risks in MG

Patients with ocular disease may be more likely to develop gMG: Study

Joana Vindeirinho,PhD avatar

by Joana Vindeirinho,PhD |

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An illustration shows a cluster of antibodies.

High levels of anti-acetylcholine receptor (AChR) antibodies — the most common self-reactive antibodies known to drive myasthenia gravis (MG) — in people with ocular MG are linked to greater odds of developing generalized MG, according to a recent study.

People with ocular MG who had high anti-AChR antibody levels also were more likely to have antibodies against the thyroid and have a thymus gland tumor (thymoma) than those with lower levels of these self-reactive antibodies.

Ocular MG patients with high anti-AChR antibody levels “should be closely monitored and encouraged to be aware of early clinical signs of life-threatening GMG [generalized MG],” the researchers wrote.

The study, “Significance of Acetylcholine Receptor Antibody Titers in Acetylcholine Receptor Antibody-Positive Ocular Myasthenia Gravis: Generalization and Presence of Thyroid Autoimmune Antibodies and Thymoma,” was published in the journal Clinical Ophthalmology.

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Investigating the impact of anti-AChR antibodies in MG

Ocular MG is an autoimmune disease characterized by weakness in the muscles that control eye and eyelid movements. Like other forms of MG, symptoms are most often caused by anti-AChR antibodies attacking AChR, a key protein for nerve-muscle communication.

Many ocular MG patients — 20% to 80% — develop muscle weakness in other parts of the body, progressing to generalized MG, usually called gMG, within two years.

Studies have shown that the presence of anti-AChR antibodies in ocular MG patients is a risk factor for gMG development. However, little is known about how the levels of these antibodies affect the risk of developing generalized MG.

To fill this knowledge gap, a team of researchers in Thailand conducted a retrospective study of a group of ocular MG patients diagnosed at the Ramathibodi Hospital, in Bangkok, from January 2012 to June 2022. Their goal was to assess the link between anti-AChR antibody levels and the odds of developing generalized MG.

Typically, about 10% to 15% of people with MG are found to have thymomas — a combination linked to a poorer prognosis. Additionally, about 20% to 30% of patients may have anti-thyroid antibodies, which can affect the success of immunomodulatory MG therapies.

With that in mind, the researchers also investigated possible associations between anti-AChR antibody levels and the presence of thymomas and anti-thyroid antibodies.

The study included 118 adults with ocular MG who were positive for anti-AChR antibodies. A majority (61.9%) of the patients were women. The patients had a mean age of 56.1 at the time of disease onset, and median levels of anti-AChR antibodies were at 3.33 nanomoles per liter (nmol/L) of blood.

At the end of follow-up, which lasted a median of 14.5 months, most — 99 individuals or 83.9% — had maintained an ocular MG diagnosis, while 19 (16.1%) had progressed to generalized MG.

Analyses showed that the odds of progressing to generalized MG were 3.66 times higher for people with AChR antibody levels of 8.11 nmol/L or higher than for those with lower antibody levels.

To the best of our knowledge, this is the first study to establish an association between AChR antibody titers in OMG [ocular MG] subjects and the presence of thyroid autoimmune antibodies and of thymoma.

CT chest scans of 106 ocular MG patients detected a thymoma in nine (8.5%). Analyses showed that high anti-AChR antibody levels (of 15.12 nmol/L or higher) were linked to a nearly fivefold higher chance of having a thymoma, compared with having lower antibody levels.

Similarly, higher anti-AChR antibody levels were linked to higher odds of having anti-thyroid antibodies. Of 79 ocular MG patients with anti-thyroid antibody information, 26 (32.9%) had anti-thyroid antibodies. Anti-AChR antibody analyses showed that those with anti-AChR antibody levels of 2.81 nmol/L or higher were more than six times more likely to also have anti-thyroid antibodies.

“To the best of our knowledge, this is the first study to establish an association between AChR antibody titers in OMG [ocular MG] subjects and the presence of thyroid autoimmune antibodies and of thymoma,” the researchers wrote.

The team urged that people with ocular MG who have high levels of anti-AChR antibodies should be monitored for any signs of gMG development, and patients themselves should be encouraged to watch out for any of those symptoms.

“In addition, we recommend that serum thyroid autoimmune antibodies and thoracic CT screening for thymoma should be performed in AChR antibody-positive OMG patients,” the researchers wrote, particularly for patients with high anti-AChR antibody levels.

Additional studies with a prospective design would be useful to further explore these associations, the team noted. Particularly helpful would be studies assessing the effect of anti-AChR antibody levels on the time from ocular MG diagnosis to progression to gMG, and including patients negative for anti-AChR antibodies.