For people with thymomas, certain risk factors, such as clusters of developing B-cells, called germinal centers, in their thymuses, may make them more likely to develop myasthenia gravis (MG), a study suggests.
Other factors that may contribute to MG development in people with thymomas include higher levels of anti-acetylcholine receptor (AChR) antibodies, altered levels of certain inflammatory signaling molecules in the blood, and being a woman younger than 50 years old, according to the study, titled “Risk factors associated with myasthenia gravis in thymoma patients: The potential role of thymic germinal centers” and published in the Journal of Autoimmunity.
Thymomas, or tumors of the thymus, are known to be associated with the development of autoimmune diseases, the most common of which is MG, estimated to affect about a third of people with thymomas. However, it is unclear what clinical factors make an individual with a thymoma more or less likely to develop MG.
Researchers in this study set out to identify some of these factors. To do this, they analyzed patient data from a group of clinics in France. Data was collected from 409 people who had thymomas and developed MG (called the MGT group), 111 people with thymomas who did not develop MG (the TOMA group), and 1,246 people who had developed MG in the absence of a thymoma.
“High incidence (78.7%) of MG among our cohort of thymoma patients was because our research team is mainly dedicated to the study of MG,” the researchers wrote. “The incidence of MG in thymoma patients is considered to be approximately 30% but is highly variable from one study to another and can range from 17 to 67%.”
It should also be noted that not all measurements were taken for all study participants; for example, levels of inflammatory markers in the blood were only measured in 14–22 people per group.
Researchers first found that there were more females in the MGT and MG groups, whereas there was a roughly even split between males and females in the TOMA group, suggesting that females may be at a greater risk of MG following a thymoma.
MGT patients were also significantly younger (under 50 years old) when they underwent a thymectomy (surgical removal of the thymus, which is standard care for thymomas) than TOMA patients, suggesting that both age and sex could be risk factors.
While almost all (98.5%) of the MGT group were positive for anti-AChR antibodies — self-targeting antibodies that are known drivers of MG — only 51.3% of the TOMA group were positive at the time of thymectomy. This suggests that the presence of anti-AChR is a risk factor for MG; the researchers even speculated that people in the TOMA group who were positive may be at a greater likelihood of developing MG after surgery and thus may require closer monitoring. Among those positive for the antibodies, the amount in the blood was not significantly different between these two groups.
The researchers also found that 58.8% of the people in the MGT group had germinal centers in their thymuses, compared with 15.6% of those in the TOMA group. Germinal centers (GCs) are clusters of B-cells — the cells that make antibodies, including the anti-AChR antibodies that drive MG — that are developing (that is, in the process of growing and making and refining antibodies). The researchers noted that younger individuals in the MGT group were more likely to have these GCs in their thymuses.
They hypothesized that GCs might participate in anti-cancer immunity, although they acknowledged that, since standard care for thymomas is a thymectomy, it’s hard to make definitive conclusions about whether these structures are protective against cancer.
Still, they reasoned that the presence of antibody-producing B-cells might set the stage for the abnormal production of self-targeting antibodies. “Consequently,” they wrote, “thymic GCs could have a negative role, favoring autoimmunity in particular.”
Researchers also found that individuals in the MGT group had higher levels of interferon gamma, interleukin-1 beta, and soluble cluster of differentiation 40 ligand in their blood. These are cytokines, signaling molecules that drive inflammation. Their precise role in MG — associated with thymomas or otherwise — may require more thorough analysis in future studies to understand.
More broadly, the researchers believe that more prospective studies should be conducted to determine the validity of these proposed risk factors, which, they suggest, could help in the management of thymomas after thymectomy.
“Early identification of patients at risk of developing MG is very important for specific follow-up after surgery,” the researchers wrote. “In addition, the benefits of early immunosuppressive treatment of these patients to prevent MG symptoms and/or to decrease their intensity should be discussed.”