Sara Rashid Chehreh Bargh1, Abbas Tafakhori2,3, Farimah Masoumi1, Farzaneh Rahmani4, Mona Ahmadi2, Afshin Namdar1, Maryam Azimi1, Parsova Tavasolian1, Sima Habibi1, Babak Zamani5, Marziyeh Maserrat2, Maryam Sadr6, Farshid Noorbakhsh1, Nima Rezaei7,8,9,10. 1. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2. Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran. 3. NeuroImmunology Research Association (NIRA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. 4. NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN), Tehran, Iran. 5. Rasul'e Akram hospital, Iran University of Medical Sciences, Tehran, Iran. 6. Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran. 7. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. rezaei_nima@tums.ac.ir. 8. Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran. rezaei_nima@tums.ac.ir. 9. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Boston, MA, USA. rezaei_nima@tums.ac.ir. 10. Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, 14194, Iran. rezaei_nima@tums.ac.ir.
Abstract
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.
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.
Entities:
Keywords:
Amyotrophic lateral sclerosis; CD25; FOXP3; IL-2Rα; Regulatory T cell; T helper
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