Scholarship 16/24443-7 - Imunorregulação, Escleroderma sistêmico - BV FAPESP
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Immunophenotypic, functional and gene evaluation of B cell subsets in patients with systemic sclerosis undergoing autologous hematopoietic stem cell transplantation

Grant number: 16/24443-7
Support Opportunities:Scholarships in Brazil - Doctorate
Start date until: September 01, 2017
End date until: October 31, 2019
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Kelen Cristina Ribeiro Malmegrim de Farias
Grantee:João Rodrigues Lima Júnior
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID
Associated scholarship(s):18/20343-3 - Evaluation of B-cell receptor repertoire in systemic sclerosis patients treated with autologous hematopoietic stem cell transplantation, BE.EP.DR

Abstract

Systemic sclerosis (ES) is an autoimmune disease of the connective tissue, characterized by microvascular lesions, associated with different degrees of fibrosis of the skin and internal organs. ES is classified into two major clinical forms; ES limited and diffuse ES. These forms are differentiated by the extent of cutaneous involvement, by the serum profile of autoantibodies and by different evolution and prognosis. The mechanisms involved in the pathogenesis of ES are not fully elucidated, however, it is known that conventional B cells, as well as regulatory B cells, play an important role in the development of the disease. In addition, the treatments available for ES are limited. Therefore, autologous hematopoietic stem cell transplantation (AHSCT) is a promising therapeutic alternative for progressive/ severe ES, preventing the progression of the disease and/or favoring the use of conventional therapy in refractory patients. The objective of the present study is to evaluate the phenotype, function and gene expression of B-cell subpopulations of ESA patients, treated by CATCH. This includes: (i) immunophenotypic evaluation of peripheral B cell subpopulations, (ii) functional analysis of purified regulatory B cells, (iii) analysis of the expression of several genes (transcription factors, cytokines, costimulatory molecules, intracellular signaling molecules) microRNAs in CD19 + B cells, (iv) production of cytokines and autoantibodies by B cells stimulated in vitro. The findings may reveal biomarkers of prognosis and/ or therapeutic response involved in this type of treatment. Our hypothesis is that, after transplantation, patients present a decrease in B-cell numbers of memory and autoantibody production and an increase in regulatory B cells, leading to involution of fibrotic skin involvement and clinical improvement. This study will help to clarify the immunological and epigenetic mechanisms of action and the benefits of AHSCT in the treatment of ES, which is necessary to improve the clinical protocol and broader application of this innovative cellular therapy, as a treatment of ES.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LIMA-JUNIOR, JOAO R.; ARRUDA, LUCAS C. M.; GONCALVES, MAYNARA S.; DIAS, JULIANA B. E.; MORAES, DANIELA A.; COVAS, DIMAS T.; SIMOES, BELINDA P.; OLIVEIRA, MARIA CAROLINA; MALMEGRIM, KELEN C. R.. utologous haematopoietic stem cell transplantation restores the suppressive capacity of regulatory B cells in systemic sclerosis patient. RHEUMATOLOGY, v. 60, n. 12, p. 5538-5548, . (16/24443-7, 13/08135-2, 18/20343-3)
LIMA-JUNIOR, JOAO R.; ARRUDA, LUCAS C. M.; GONCALVES, MAYNARA S.; DIAS, JULIANA B. E.; MORAES, DANIELA A.; COVAS, DIMAS T.; SIMOES, BELINDA P.; OLIVEIRA, MARIA CAROLINA; MALMEGRIM, KELEN C. R.. utologous haematopoietic stem cell transplantation restores the suppressive capacity of regulatory B cells in systemic sclerosis patient. RHEUMATOLOGY, v. 60, n. 12, p. 5538-5548, . (18/20343-3, 16/24443-7, 13/08135-2)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
LIMA JÚNIOR, João Rodrigues. Immunophenotypic, functional and gene evaluation of B cell subsets in patients with systemic sclerosis undergoing autologous hematopoietic stem cell transplantation. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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