Thymectomy surgery may cause long-term immune changes in MG
Procedure led to T-cell reductions, changes in cytokine secretions
Surgery to remove the thymus gland led to a long-term reduction in levels of immune T-cells and to temporary changes in levels of proteins involved in regulating immune and inflammatory responses in people with myasthenia gravis (MG), a study shows.
There were no significant effects on the levels of antibodies and other immune proteins, however.
“These findings suggest that thymectomy has a lasting impact on cellular immunity and cytokine secretion [production and release], with potential implications for immune system function and the risk of infections in MG patients,” the study’s researchers wrote. The study, “Delving into immune modulation: thymectomy in myasthenia gravis,” was published in the Journal of Cardiothoracic Surgery.
MG is caused by self-reactive antibodies that target proteins involved in nerve-muscle communication, leading to muscle weakness and other symptoms. The thymus gland, an organ of the immune system, is believed to contribute to producing the self-reactive antibodies that drive MG.
Thymectomy is a type of surgery commonly performed in people with MG, particularly among those who also have a thymoma, or tumor in the thymus gland. The surgery “has been proved to diminish the necessity for immunosuppressive therapy and increase long-term remission,” according to the researchers.
Despite its efficacy in treating MG, the surgery may have an impact on the function of the immune system, with some studies suggesting it may increase the risk of infections and cancer.
Effects of thymectomy on immune response
Here, researchers in China studied MG patients to learn more about the long-term effects of thymectomy surgery. The study was made up of 44 patients — 14 who had a thymectomy and 30 who didn’t and served as a control group. The patients in both groups received treatment that consisted of pyridostigmine (sold as Mestinon) and glucocorticoids. Both groups’ patients were of similar age and disease duration. The proportion of men was higher in the thymectomy group (57.1% vs. 36.7%), but the overall sex ratio wasn’t significantly different than the control group’s.
In both groups, most patients had a thymoma (85.7% vs. 76.7%) and self-reactive antibodies targeting acetylcholine receptors (92.9% vs. 86.7%), the most common type of MG-causing self-reactive antibody. Most patients in both groups had generalized MG (85.7% vs. 46.7%), while ocular MG was only seen in the control group.
Before the surgery, both patient groups had similar levels of immune T-cells, including CD3-, CD4-, and CD8-positive cells. These cell levels dropped compared with before surgery a month after treatment in the two groups and remained stable. However, the CD4/CD8 ratio, an indicator of immune health, was significantly lower in those who had a thymectomy after six months and a year. Levels of CD4-positive T-cells were also significantly lower in those who had surgery over controls after a year.
No significant differences were seen between the groups before or after treatment in levels of different antibody classes (IgM, IgG, and IgA) or in those of proteins from the complement cascade (C3 and C4), a part of the immune system. All markers remained stable over time.
The levels of the pro-inflammatory cytokines interleukin (IL)-2, IL-6, interferon gamma, and TNF-alpha decreased a month after treatment in both groups. However, the decrease was significantly higher in the thymectomy group for interferon gamma and TNF-alpha. Cytokine levels generally stabilized three or six months after treatment.
Conversely, levels of IL-4, an anti-inflammatory cytokine that can suppress the production of pro-inflammatory molecules, were higher in the thymectomy group after a year.
“This study demonstrated that thymectomy significantly impacts immune function and cytokine levels in MG patients, with long-term decreases in [CD4-positive cell] levels and shifts in the CD4/CD8 ratio. While thymectomy can improve MG symptoms, it may also lead to immune alterations. Close monitoring of immune function and infection risk is recommended for MG patients following thymectomy,” the researchers wrote.
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