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

• Published in: Irish journal of medical science Vol. 187; no. 4; pp. 1065 - 1071
• Main Authors: Rashid Chehreh Bargh, Sara, Tafakhori, Abbas, Masoumi, Farimah, Rahmani, Farzaneh, Ahmadi, Mona, Namdar, Afshin, Azimi, Maryam, Tavasolian, Parsova, Habibi, Sima, Zamani, Babak, Maserrat, Marziyeh, Sadr, Maryam, Noorbakhsh, Farshid, Rezaei, Nima
• Format: Journal Article
• Language: English
• Published: London Springer London 01-11-2018
• Subjects: Adult; Aged; Amyotrophic Lateral Sclerosis - blood; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - immunology; Disease Progression; Family Medicine; Female; Forkhead Transcription Factors - biosynthesis; Forkhead Transcription Factors - blood; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - immunology; Gene Expression; General Practice; Humans; Interleukin-2 Receptor alpha Subunit - biosynthesis; Interleukin-2 Receptor alpha Subunit - blood; Interleukin-2 Receptor alpha Subunit - genetics; Interleukin-2 Receptor alpha Subunit - immunology; Internal Medicine; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Male; Medicine; Medicine & Public Health; Middle Aged; Original Article; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Amyotrophic lateral sclerosis; IL-2Rα; CD25; FOXP3; T helper; Regulatory T cell
• ISSN: 0021-1265; 1863-4362
• DOI: 10.1007/s11845-018-1793-2

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.