| Grant number: | 16/24443-7 |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| Start date: | September 01, 2017 |
| End date: | 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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