In Thymoma-associated MG, More Hospitalizations Tied to Antibodies

Severe relapses more likely for patients with anti-titin antibodies

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by Andrea Lobo |

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The presence of anti-titin antibodies, a type of blood protein, in patients with thymoma-associated myasthenia gravis (MG) is related to more frequent hospitalizations, a study in South Korea has found.

Thymoma is a type of tumor occurring in the thymus gland, a small organ in the chest that produces infection-fighting white blood cells.

“This may implicate that [MG] patients with both the thymoma and anti-titin antibody are likely to be uncontrolled or experience more frequent relapses, which are severe enough to require hospitalization or ER visit,” the researchers wrote.

Frequent relapses requiring hospital care negatively impact the quality of life of people with MG — and such hospitalization “also imposes a considerable financial burden to the patients,” the team noted.

“Thus, careful assessment and monitoring strategy could be required in patients with thymoma-associated MG with anti-titin antibody to manage frequent relapses,” they wrote.

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More hospitalizations for patients with anti-titin antibodies

Published in the journal Frontiers in Neurology, the study “Anti-titin antibody is associated with more frequent hospitalization to manage thymoma-associated myasthenia gravis” detailed the researchers’ findings.

MG is an autoimmune disease that affects the communication between nerve and muscle cells at the neuromuscular junction — the region where both cell types come into contact. The disease occurs when the immune system produces antibodies that target proteins that are critical for nerve-muscle communication.

Its main symptoms are muscle weakness and fatigue, and the disease usually becomes evident during adulthood. Patients frequently experience symptom worsening that results in greater disability, fatigue, and poorer quality of life.

The majority of people with generalized myasthenia gravis — about 85% — have antibodies against acetylcholine receptors, which are found on the surface of muscle cells. Other antibodies also have been identified, some targeting proteins inside muscle cells.

Such antibodies include those targeting titin, a structural muscular protein that is important for the contraction of striated muscles.

Anti-titin antibodies are present in 20–30% of patients with anti-acetylcholine receptor antibodies, and are more frequent in those with thymoma-associated or late-onset MG.

Previous studies have associated anti-titin antibodies with MG severity and frequent clinical worsening. These patients typically are more likely to receive immunosuppressive treatments and are less likely to reach disease remission.

Now, researchers in South Korea assessed the frequency of disease worsening and severity in patients with or without anti-titin antibodies.

The team reviewed medical records of patients diagnosed with thymoma-associated MG who visited the hospital’s neurology department between May 2017 and September 2020.

Of the 64 patients evaluated,  31 (48.4%) had anti-titin antibodies and 33 (51.6%) did not. The age at disease onset was similar in both groups, as were the proportions of male and female patients, and the levels of anti-acetylcholine receptor antibodies.

Regarding treatment, the proportion of patients receiving intravenous immunoglobulin therapy was higher in the titin-positive group (45.2% vs. 21.2%). Similarly, the proportion of patients given treatment with immunosuppressive agents tended to be higher in the titin-positive group than in the titin-negative group (74.2% vs 51.5%).

All 64 patients underwent surgery to remove the thymus, a procedure called thymectomy. In 52 patients, the pathological (disease) subtype and the Masaoka staging of the thymoma — the most important determinant for survival — were identified and did not differ between the groups.

The proportion of patients with a higher stage tumor tended to be greater in the titin-positive group (38.7% vs. 15.2%). Also, the proportion of patients receiving systemic chemotherapy was higher in the titin-positive group compared with the titin-negative group (38.7% vs. 6.1%).

Thymoma recurrence also was more frequent in the titin-positive group (32.2% vs. 9.1%).

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Thymoma a factor in hospitalizations

The frequency of hospital treatments was assessed in patients who were followed for at least one year (58 patients total, with 29 in each group). The proportion of patients experiencing MG-related hospitalizations or emergency room (ER) visits was higher in the titin-positive group (82.8% and 55.2%, respectively) than in the titin-negative group (48.3% and 20.7%).

The main cause for hospitalization was symptom worsening (97.8%), with medication toxicity accounting for 2.2% of cases. For visits to the ER, shortness of breath or chest discomfort was the main reason (61.5%), followed by limb weakness (19.2%), and bulbar symptoms (9.6%). Bulbar symptoms encompass those that affect the muscles in the head and neck, and might lead to speech, chew, and swallow impairments.

Multiple admissions to the hospital occurred in 50% of the 58 patients, and were more frequent in the titin-positive group than in the titin-negative group (69% vs. 31 %). A statistical analysis associated multiple hospitalizations with duration of follow-up, high Masaoka staging, systemic chemotherapy, and the presence of anti-titin antibodies.

A second statistical analysis confirmed the presence of anti-titin antibodies was associated with multiple hospitalizations, after adjusting for sex, period of follow-up, age at disease onset, systemic chemotherapy, and Masaoka staging.

“Our results suggest that the patients with thymoma-associated MG having anti-titin antibody are more likely to experience more frequent hospitalization or ER visit to control MG than those without anti-titin antibody,” the researchers wrote.

Moreover, titin-positive patients are more likely to use immunosuppressive therapies.

According to the team, “the presence of anti-titin antibody could be utilized in predicting treatment response in patients with thymoma-associated MG.”