Th17 and effector CD8 T cells relate to disease progression in amyotrophic lateral sclerosis: a case control study

The immune system has garnered attention due to its association with disease progression in amyotrophic lateral sclerosis (ALS). However, the role of peripheral immune cells in this context remains controversial. Here, we conducted single-cell RNA-sequencing of peripheral blood mononuclear cells to comprehensively profile immune cells concerning the rate of disease progression in patients with ALS. Our analysis revealed increased frequencies of T helper 17 cells (Th17) relative to regulatory T cells, effector CD8 T cells relative to naïve CD8 T cells, and CD16^highCD56^low mature natural killer cells relative to CD16^lowCD56^high naïve natural killer cells in patients with rapidly progressive ALS. Additionally, we employed serum proteomics through a proximity extension assay combined with next-generation sequencing to identify inflammation-related proteins associated with rapid disease progression. Among these proteins, interleukin-17 A correlated with the frequency of Th17, while killer cell lectin-like receptor D1 (CD94) correlated with the frequency of effector CD8 T cells. These findings further support the active roles played by these specific immune cell types in the progression of ALS.