Page 75 - The autoimmune hypothesis of narcolepsy and its unexplored clinical features M.S. Schinkelshoek

reliably. As several studies point out, immune cells crossing the blood-brain barrier are of special interest and technical innovations should make in-depth assessment of the immune cell composition in cerebrospinal fluid possible in the near future.
Additionally, it could be argued that differences between groups might be driven by single patients. We extensively checked our results for outliers. However, variability in the composition of the immune system between patients is high. Validation of our results in other cohorts of NT1 patients is therefore important to confirm the value of our findings.
Our results do not allow for inferring causality. The technique that was used is exploratory and should lead to focused experiments on the role of the identified enriched immune cell populations we identified have in the presumed autoimmune response leading to the destruction of hypocretin-producing neurons. Performing functional experiments on the immune cell populations discovered in this study could serve as a starting point for identifying the mechanisms involved in the autoimmune response leading to the destruction of hypocretin-producing neurons. Assessing immune cell reactivity to antigens of interest (such as hypocretin, H1N1 or other, still unknown antigens) with the identified NT1-specific immune cell populations seems a promising strategy, which allows for diminishing the background noise that other immune cells might have caused in previous experimental antigen-centered research on the autoimmune response leading to NT1.
Conclusions
Populations of memory CD4+ and CD8+ T cells and regulatory CD4+ T cells are more frequently found in the peripheral blood of NT1 patients than in healthy HLA-DQB1*06:02-matched controls. Differences in major immune cell lineages are absent in our sample. Additionally, differences in immune cell composition between NT1 patients with recent disease onset and those longer after disease onset are limited. These findings point towards multifaceted immune activation in NT1 patients. Performing functional experiments on the immune cell populations discovered in this study could serve as a starting point for identifying novel mechanisms driving the autoimmune response leading to the destruction of hypocretin-producing neurons.
Immune cell composition in peripheral blood
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