ALS Patients’ Immune Cells May Provide Insight into Disease Progression

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease that involves neuroinflammation and T cell infiltration in the nervous system, ultimately leading to muscle paralysis. While a lot of work has emerged researching the mechanisms behind ALS, the contribution of T cell responses in the pathology of the disease is not fully understood. To learn more, researchers from the Karolinska Institutet uncovered how these T cells might play a protective role in rapid disease progression.

The team’s work, published in the journal Nature Communications, began between March 2016-2020, where they collected fresh blood and cerebrospinal fluid (CSF) from a cohort of 89 participants in Stockholm recently diagnosed with ALS. All the patients were monitored and followed until October 2020. 

The researchers utilized flow cytometry to define T cell subsets in blood and CSF samples collected from each patient at the time of diagnosis to identify immune markers associated with ALS survival.

Their findings revealed that T cell phenotypes at the time of diagnosis were good predictors of disease outcome. High proportions of CD4⁺FOXP3⁻ effector T cells in the blood and CSF were associated with poor survival. In contrast, high frequency of activated regulatory T (Treg) cells, plus a high ratio between activated and resting Treg cells in the blood, were associated with better survival. T cell subsets measured in both blood and CSF were also predictive of disease progression rate post-ALS diagnosis.

These findings provide new evidence for the involvement of T cells in the course of the disease, as well as reveal how certain types of effector T cells accumulate in the cerebrospinal fluid of ALS patients. “The study could contribute to the development of new treatments that target immune cells to slow down the course of the disease,” says first author Solmaz Yazdani, a doctoral student at the Institute of Environmental Medicine at Karolinska Institutet.

The team was able to make a detailed comparison of T cell subsets in CSF and blood to better understand whether the immune profiles measured in peripheral blood are representative of the immune profile of the central nervous system. They note, however, that the correlations of blood- and CSF-based T cell markers had weak predictive power in either direction, so future studies may benefit from assessing both compartments to gain a more comprehensive understanding of ALS’ immunological processes, as well as other brain diseases.

In addition to those efforts, the team seeks to determine precisely how T cells contribute to the course of the disease in future work. “We have plans to collect samples from these individuals to study changes in the immune cells over time. In addition, we want to study effector T cells in more detail to understand their role in ALS.”