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Evaluation of T Regulatory Lymphocytes Transcription Factors in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Patients

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Abstract

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an aggressive neurological disease. The CD4+CD25+ T cell population plays pivotal roles in the maintenance of immunological tolerance and prevention of such autoimmune diseases. In the current study, proviral load (PVL), factor forkhead box p3 (Foxp3), and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) gene expression and regulatory T cells (Tregs) counts of 21 HAM/TSP patients and 16 HTLV-1 healthy carriers (ACs) were measured using real-time PCR, TaqMan method, and flow cytometry. The demographic, history of disease, and severity of myelopathy were assessed by a checklist and the Osame motor disability score (OMDS). The mean OMDS for HAM/TSP was 4.82 ± 2.37 which had no significant correlation with Treg count or the expression of Foxp3, GITR, and PVL. The CD4+CD25+ cell counts had no significant differences between HAM/TSP and ACs. Findings revealed a higher PVL in HAM/TSPs (313.36 copies/104) compared to ACs (144.93 copies/104, p = 0.035). The Foxp3 and GITR mRNA levels were lower in HAM/TSP patients (11.78 and 13.80, respectively) than those in healthy carriers (18.44 and 21.00, p = 0.041 and 0.03, respectively). There was a significant correlation between Treg frequency and Foxp3 gene expression (R = 0.67, p = 0.006) and GITR and Foxp3 (R = 0.84, p = 0.042) in HAM/TSP patients. Furthermore, the transcription factors have strong correlations with CD4+CD25+ T cell frequencies. These findings suggest that HTLV-1 infection can modify the expression of main functional transcription factors, FOXP3 and GITR, which may lead to immune response deterioration of Tregs and consequently HAM/TSP manifestation.

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Acknowledgements

The authors do appreciate the great help of the Neurology Department of Ghaem Hospital and the support of the Iranian Academic Center for Education, Culture & Research (ACECR), Mashhad, Iran. This study was a subject of a thesis for a MD, pathology student and granted by the vice chancellor for Research, Mashhad University of Medical Sciences, Mashhad, Iran. We specially thank for the valuable help of Dr. Arman Mosavat. This manuscript is dedicated to the memory of Dr. Ali Sadeghian as a friend, mentor, and colleague.

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Authors and Affiliations

  1. Research Center for HIV/AIDS, HTLV and Viral Hepatitis, Iranian Academic Center for Education, Culture & Research (ACECR), Mashhad Branch, Mashhad, Iran

    Sanaz Ahmadi Ghezeldasht & Seyyed Ali Akbar Shamsian

  2. Immunology Research Center, Inflammation and Inflammatory Diseases Division, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Hamed Sadeghian, Mahmoud Reza Azarpazhooh, Houshang Rafatpanah & Seyyed Abdolrahim Rezaee

  3. Immunology Research center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahmood Mahmoodi

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  1. Sanaz Ahmadi Ghezeldasht
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Correspondence to Seyyed Abdolrahim Rezaee.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the ethics committee of Mashhad University of Medical Sciences (No 88134).

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Ghezeldasht, S.A., Sadeghian, H., Azarpazhooh, M.R. et al. Evaluation of T Regulatory Lymphocytes Transcription Factors in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Patients. Appl Biochem Biotechnol 182, 1403–1414 (2017). https://doi.org/10.1007/s12010-017-2406-7

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