AChR Antibody Titers May Help Predict Conversion to Generalized Myasthenia Gravis

Antibody titers in patients with acetylcholine receptor (AChR) antibody–positive ocular myasthenia gravis (MG) may provide meaningful clues about the risk that a patient will develop generalized MG, according to a new report.

The study, published in Clinical Ophthalmology, also suggests that certain levels of thyroid autoimmune antibodies may hold prognostic value.

About half of people with MG present with purely ocular symptoms of the disease, noted the study authors. Such cases can be challenging to diagnose, since the symptoms of the disease can also be explained by several other conditions. In such cases, AChR antibody testing can provide diagnostic clarity, as most patients with MG test positive for AChR antibodies.

Even with an accurate diagnosis and emerging treatment options, a significant proportion of people with ocular MG will progress to the generalized form of the disease within 2 years. The authors noted that previous studies have suggested older age at onset, history of smoking, and the presence of thymoma are risk factors for conversion from ocular MG to the generalized form of the disease, known as GMG. However, evidence suggests antibody titers might also be meaningful prognostic factors.

“Although many studies showed that seropositivity to AChR antibody was one of the significant risk factors for GMG conversion, the association between AChR antibody titers and the conversion to GMG has been scarcely studied,” they wrote.

Similarly, the investigators said there has been little research to delve into how AChR antibody titer levels might be associated with the presence of thyroid autoimmune antibodies and the presence of thymoma.

“Therefore, we aimed to evaluate the association in AChR antibody-positive OMG subjects between AChR antibody titers and conversion to GMG, the presence of thyroid autoimmune antibodies, and the presence of thymoma,” they wrote.

They decided to retrospectively review the medical records of 118 people with AChR antibody–positive ocular MG. In their analysis, they defined thyroid autoimmune antibodies as the presence of at least 1 of 3 types of antibodies: thyroid peroxidase antibody, thyroid-stimulating hormone receptor antibody, or thyroglobulin antibody.

After a median follow-up of 14.5 months, the investigators looked to see how patients’ antibody levels related to their clinical outcomes.

Overall, the cohort had a median AChR antibody titer level of 3.33 nmol/L, and at the end of the follow-up period, just 19 participants (16.10%) had converted to GMG. The investigators found that an AChR antibody titer of at least 8.11 nmol/L was associated with a greater risk of GMG conversion (odds ratio [OR], 3.66; 95% CI, 1.19-11.26; P = .023).

Thyroid autoimmune antibody data were available for 79 patients. Of those, 26 patients (32.91%) tested positive for thyroid autoimmune antibodies. The authors said that an AChR antibody titer level of at least 2.81 nmol/L was associated with the presence of thyroid autoimmune antibodies (OR, 6.16, 95% CI, 1.79-21.22; P = .004).

In addition, they found that 9 of the 106 patients for whom CT data were available had thymoma. In those cases, an AChR antibody titer of at least 15.12 nmol/L was linked with the presence of thymoma (OR, 4.97, 95% CI, 1.10-22.48; P = .037).

Taken together, the study investigators said the data suggest that AChR antibody titer levels should be considered in patients with ocular MG.

“We recommend that those with AChR antibody titers ≥ 8.11 nmol/L, and who thereby are at a greater risk of conversion to GMG, should be closely monitored and encouraged to be aware of early clinical signs of life-threatening GMG,” they wrote.

They also said patients whose AChR antibody titers exceed 2.81 or 15.12 nmol/L should be tested for serum thyroid autoimmune antibodies or undergo thoracic CT screening.

Reference

Supawongwattana M, Vanikieti K, Jindahra P, Padungkiatsagul T. Significance of acetylcholine receptor antibody titers in acetylcholine receptor antibody-positive ocular myasthenia gravis: generalization and presence of thyroid autoimmune antibodies and thymoma. Clin Ophthalmol. 2023;17:649-656. doi:10.2147/OPTH.S402181