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T helper 17 and regulatory T-cell profile and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in pediatric patients with beta-thalassemia
Affiliation:1. Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran;2. Pediatric Cell and Gene Therapy Research Center, Gene, Cell and Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran;3. Research Center for Immunodeficiencies, Children''s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;4. Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran;5. Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran;6. Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran;7. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran;8. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;9. Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran;10. Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran;1. Department of Transfusion Medicine, Histocompatibility and Molecular Biology, Jaypee Hospital, Noida, UP 201301, India;2. Department of Histocompatibility and Molecular Biology, Jaypee Hospital, Noida,UP 201301, India;3. Department of Transfusion Medicine, Jaypee Hospital, Noida, UP 201301, India;4. Kidney Transplant Programme, Department of Urology and Kidney Transplant, Jaypee Hospital, Noida, UP 201301, India;5. Department of Nephrology and Kidney Transplant, Jaypee Hospital, Noida, UP 201301, India;1. Department of General, Visceral, and Transplant Surgery, LMU University Hospitals, Ludwig-Maximilians-Universität Munich, Marchioninistraße 15, 81377 Munich, Germany;2. Walter-Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität Munich, Marchioninistraße 15, 81377 Munich, Germany;3. Institute of Laboratory Medicine, LMU University Hospitals, Ludwig-Maximilians-Universität Munich, Marchioninistraße 15, 81377 Munich, Germany;1. Department of Neurology, Guangzhou First People''s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China;2. Department of Neurology, Guangzhou First People''s Hospital, Guangzhou Medical University, Guangzhou 510180, China;3. Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510180, China;1. Department of Neurology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai City, Shandong Province, China;2. Department of Urology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai City, Shandong Province, China;1. Department of Respiratory Medicine, Tokyo Women''s Medical University, Tokyo, Japan;2. Department of Infectious Diseases, Tokyo Women''s Medical University, Tokyo, Japan;3. Department of Infection Prevention and Control, Tokyo Women''s Medical University, Tokyo, Japan;4. Department of Pharmacy, Tokyo Women''s Medical University, Tokyo, Japan;5. Department of Urology, Tokyo Women''s Medical University, Tokyo, Japan;6. Department of General Medicine, Tokyo Women''s Medical University, Tokyo, Japan;7. Department of Surgery, Institute of Gastroenterology, Tokyo Women''s Medical University, Tokyo, Japan;8. Department of Hematology, Tokyo Women''s Medical University, Tokyo, Japan;1. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;2. Department of Anatomical Sciences, Sarab Faculty of Medical Sciences, Sarab, Iran;3. Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran;4. Medical and molecular genetics, Ataturk University, Erzurum, Turkey;5. Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;6. Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Abstract:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment option for hereditary hemoglobin disorders, such as beta-thalassemia; However, this procedure is not without constraints, mainly engendering complications such as acute graft-versus-host disease (aGvHD), chronic GvHD (cGvHD), and susceptibility to infections. The clinical outcomes of allo-HSCT are highly dependant on the quality and quantity of T-cell subsets reconstitution. Following the allo-HSCT of six pediatric patients afflicted with beta-thalassemia, their mononuclear cells were isolated, and then cultured with a combination of phorbol myristate acetate (PMA)/ionomycin and Brefeldin A. The content of CD4 T-cell subsets, including T helper 17 (Th17) cells and regulatory T cells (Tregs), were determined by specific conjugated-monoclonal antibodies three and six months post-HSCT. An increased frequency of total CD4 T-cells, Tregs and Th17 cells was observed at day 90 and 180 after allo-HSCT, albeit the numbers were still lower than that of our healthy controls. In patients who developed cGvHD, a lower Th17/Treg ratio was observed, owing it to a decreased proportion of Th17 cells. In conclusion, creating balance between Th17 and Treg subsets may prevent acute and chronic GvHD in patients after allo-HSCT.
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