First author Kameron Kooshesh became intrigued by open questions about the adult thymus during a second-year neurology lecture at Harvard Medical School. He learned that surgical removal of the thymus is recommended in patients with the autoimmune disease myasthenia gravis as a way to halt T-cell-induced immune destruction of nerve endings. “And yet, clinical instruction on the surgery wards taught me that the thymus is thought to be vestigial in adults,” Kooshesh said. “These two philosophies seemed diametrically opposed, and I yearned to learn more.”
For the study, Kooshesh mined data from 1,146 adult patients who had undergone thymus removal, alongside demographically matched control patients who had undergone similar surgeries but kept their thymus. Kooshesh and Scadden worked in collaboration with Brody Foy, a biostatistician who helped direct the team’s statistical queries around the epidemiology of thymectomy patients, and Karin Gustafsson, an expert in T-cell biology. David Sykes at MGH helped the team facilitate patient blood draws.
In an analysis involving all patients with more than five years of follow-up, the rate of death was higher in the thymectomy group than in the general U.S. population — 9 percent vs. 5.2 percent, as was death due to cancer, or 2.3 percent vs. 1.5 percent.
In a subgroup of patients in whom T-cell production was measured, those who had had their thymus removed had less new production of T-cells, including both helper and cytotoxic T-cells. Those patients also had higher levels of pro-inflammatory cytokines, which are small signaling proteins associated with autoimmunity and cancer, in their blood.
“The magnitude of death and cancer in patients who had undergone thymectomy was the biggest surprise for me,” said Kooshesh, now an internal medicine resident at MGH. “The more we dug, the more we found: The results suggested to us that the lack of a thymus appears to perturb basic aspects of immune function.”
The analysis was facilitated by recent advances in rapid genetic sequencing of T-cell receptors (TCRs). The technology, called TCR sequencing, has enough resolution to allow scientists to not only identify different types of T cells, but also measure their diversity as a population overall.
The Daily Gazette
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