Samples from deceased brain donors reveal specific T-cells that can target orexin/hypocretin-expressing cells.
Key takeaways:
- A study of donor brains found that specific CD4 T-cells were 11 times higher in the affected brain region, with features that can specifically target cells that express orexin/hypocretin.
- Identifying the autoimmune mechanism could shift future research toward blocking the immune activity to prevent narcolepsy onset, rather than solely treating symptoms.
Researchers at the Netherlands Institute for Neuroscience have found evidence that type 1 narcolepsy is caused by the body’s own immune system, confirming a long-held hypothesis in the sleep medicine field.
For over two decades, experts have known that narcolepsy is caused by the reduction of orexin (also known as hypocretin), a brain chemical that helps regulate wakefulness and sleep. Orexin is released throughout the brain by a small cluster of cells in the brain’s hormone centers. However, the exact mechanism behind this reduction in people with narcolepsy type 1 had not been confirmed.
“There are so many hints that narcolepsy is caused by the body’s own immune system; it has been associated with other autoimmune diseases; there is a strong genetic link, and it can be triggered by influenza,” says Ling Shan, PhD, MSc, first author and researcher in the Swaab group at the Netherlands Institute for Neuroscience, in a release.
Because the cells expressing orexin reside deep in the human brain, finding evidence of an autoimmune disorder has been difficult. Utilizing samples from four deceased brain donors with narcolepsy from the Netherlands Brain Bank, researchers examined the narcoleptic brain to confirm the immune system’s role in orexin cell loss.
The research focused on T-cells, specifically searching for CD4 T-cells, which coordinate immune reactions and indicate a chronic autoimmune response. The study found that these specific CD4 T-cells were 11 times higher in the region compared to other types of T-cells. Upon closer examination, researchers found that the heightened number of CD4 T-cells expressed specific features that allowed them to infiltrate the area and specifically target the cells expressing hypocretin.
“After such a long time, we finally have conclusive evidence that narcolepsy type 1 is a result of the body’s own immune system,” says Shan in a release.
Confirming narcolepsy as an autoimmune disease is significant for directing future research. While current medications for narcolepsy only combat symptoms without offering a cure, this discovery opens new therapeutic avenues.
“Researchers in this field are rushing into this as well,” says Shan in a release. “If we find a way to block this immune activity before it starts, we could potentially prevent narcolepsy from the beginning.”
The work was conducted in collaboration with Dr Rolf Fronczek from LUMC and Dr Joost Smolders from the NIN neuroimmunology group and Erasmus UMC. The findings were published in the Annals of Neurology.
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