Dr. Kevin C. O’Connor is an Associate Professor of Neurology and Immunobiology at Yale University School of Medicine and the Vice Chair of the MGFA Scientific Advisory Board.
Thymectomy is a procedure to remove the thymus, a small gland located behind the sternum (breastbone) that helps the immune system develop. In most people, the thymus does its work while you are young, helping develop T cells as your body matures. As you age, the thymus involutes (shrinks) as it becomes essentially inactive.
In some people, however, the thymus increases in size, possibly due to a combination of genetic and environmental factors, but the causes are not fully understood. The increase in size can be due an infiltrate of lymphocytes (immune cells), a condition called thymic lymphofollicular hyperplasia. The infiltrating lymphocytes often organize in the same way as is found in lymph nodes. In some patients with MG, these infiltrating lymphocytes are self-reactive and include those producing acetylcholine receptor (AChR) autoantibodies, which cause MG.
About 60-70% of AChR-type MG patients have thymic lymphofollicular hyperplasia. In these patients, it’s clear that the thymus is harboring cells related to MG pathology. Because of this correlation, thymectomy has been recommended to some patients. If the thymus is harboring cells that cause MG symptoms, then removing it should also remove the cells causing the disease. Yet physicians have found patients with thymectomy take a while to feel better, and that symptoms never fully disappear.
In research recently published in the Proceedings of the National Academy of Sciences, colleagues and members of my laboratory set out to find out why. We know that immune cells – B and T cells – are mature in lymph nodes and then disperse throughout the body. We designed our study to test whether this same process was true for the thymus-infiltrating B cells in MG patients.
For the study, we took blood and tissue samples at the same time patients were getting a thymectomy. Then we took blood again years later. Using a sophisticated approach that allowed us to identify clones (copies of one original B cell), we found B cell clones in the thymus and in the blood at the time of the thymectomy. One and two years later, the clones were still in the patient’s blood.
Our interpretation is that these persistent B-cell clones, present in the blood after thymectomy, contribute to disease in MG patients. Thus, removing the thymus improves disease burden but does not eliminate it; suggesting that patients will need other treatment options as well to manage their disease.
*This article shares study results and is not meant to be medical advice. Talk to your physician if you have questions about how this study’s findings may affect your individual course of treatment.