Evaluation of regulatory T lymphocytes and IL2Ra and FOXP3 gene expression in peripheral mononuclear cells from patients with amyotrophic lateral sclerosis.

Background: Loss of neuroprotective role of CD4 ⁺ helper T cells, regulatory T cells, and M2 microglia constitutively results in the rapid neural death in the "rapidly progressive phase" of amyotrophic lateral sclerosis (ALS).
Aim: We aimed to investigate relative count of CD4 ⁺ and regulatory T lymphocytes and expression level of IL2Ra and FOXP3 genes in peripheral blood mononuclear cells (PBMCs) from patients with ALS.
Method: We performed a flow cytometric analysis on PBMC from 38 patients with ALS and 32 controls to determine the count of CD4 ⁺ and CD4 ⁺ CD25 ⁺ cells. Quantitative real-time PCR analyses were implemented to determine the level of expression of FOXP3 and IL-2Rα (CD25) genes in the peripheral blood mononucleated cells.
Results: We found a significant higher proportion of CD4 ⁺ T cells (p value < 0.001), along with a significantly reduced proportion of CD4 ⁺ CD25 ⁺ Treg cells (p value = 0.001, p value = 0.02), in the peripheral blood of patient's with ALS.
Conclusion: The results of our study are in line with the hypothesis that in the early phase of ALS, neuroprotective helper T cells infiltrate in the affected areas in the lumbar spinal cord. This was reflected in higher peripheral percentage of CD4 ⁺ helper T cells and higher expression of FOXP3 and IL-2Rα. The observed demise in the number of active CD4 ⁺ CD25 ⁺ regulatory T cells might indicate early signs of progression to later stages of ALS in our study group. Interestingly, disease duration was the sole independent significant determining factor that predicted CD4+CD25+ regulatory T cell counts in the peripheral blood of patients at various stages of ALS, according to a logistic regression model.