Tregs levels and phenotype modifications during Amyotrophic Lateral Sclerosis course

Area of Science:

• Immunology
• Neuroscience
• Clinical Medicine

Background:

• T regulatory cells (Tregs) are crucial for immune homeostasis and have been implicated in Amyotrophic Lateral Sclerosis (ALS) pathogenesis.
• Reduced or dysfunctional Tregs are observed in fast-progressing ALS cases, suggesting a potential role in disease progression.

Purpose of the Study:

• To longitudinally evaluate changes in Treg levels and phenotypes in ALS patients over 54 weeks.
• To investigate associations between Treg dynamics and clinical markers of ALS progression, including ALSFRS-r and FVC.
• To identify potential clinical and biological modifiers of Treg percentages and concentrations.

Main Methods:

• Quantification of total Tregs and characterization of Treg surface markers (CD38, CD39, CXCR3, PD1) at five time points over 54 weeks in 21 ALS patients.
• Analysis of longitudinal Treg data using repeated measures mixed models.
• Investigation of correlations between Treg levels and ALS progression measures (ALSFRS-r, FVC).

Main Results:

• Treg levels showed no significant average change over the 54-week study period.
• A decrease in PD1+Tregs and an increase in CD39+Tregs were observed longitudinally.
• Male sex, cholesterol, and monocyte levels were associated with changes in Treg percentages or concentrations.
• Treg concentrations demonstrated a modest association with FVC decline but not with ALSFRS-r decline.

Conclusions:

• Treg numbers are stable in ALS patients and may have limited utility as pharmacodynamic biomarkers for ALS clinical trials.
• Longitudinal changes in Treg phenotypes, specifically the decrease in PD1+Tregs, warrant further investigation for their role in ALS progression and therapeutic potential.