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Evaluation of B-cell receptor repertoire in systemic sclerosis patients treated with Autologous Hematopoietic Stem Cell Transplantation

Grant number: 18/20343-3
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): January 01, 2019
Effective date (End): June 30, 2019
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Kelen Cristina Ribeiro Malmegrim de Farias
Grantee:João Rodrigues Lima Júnior
Supervisor abroad: Deborah Dunn-Walters
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Local de pesquisa : University of Surrey, England  
Associated to the scholarship:16/24443-7 - Immunophenotypic, functional and gene evaluation of b cell subsets in patients with systemic sclerosis undergoing Autologous Hematopoietic Stem Cell Transplantation, BP.DR

Abstract

Autologous hematopoietic stem cell transplantation (AHSCT) has emerged as a novel therapy for systemic sclerosis (SSc) patients and induces long-term disease remission. In the last years, few works have reported the reconstitution of B-cell subsets after AHSCT. However, the assessment of B-cell receptor (BCR) diversity after AHSCT needs to be ascertained. Preliminary results of our group showed an increase of newly-generated naïve B-cells after AHSCT. In addition, relapsing patients displayed a fewer counts of naïve B-cells before transplantation and during follow-up compared to responder patients suggesting that repertoire renewal of B-cell was associated with favourable clinical outcomes. The goal of this project is to evaluate the Immunoglobulin Heavy Chain (IGH) and Light Chain (IGL) diversity in SSc patients that underwent AHSCT and to correlate the results to the clinical responses of SSc patients after transplantation. We will evaluate the BCR repertoire by next-generation sequencing (NGS) at baseline and different time points post-transplantation. This study will help to clarify the immunological mechanisms involved with the AHSCT therapy for SSc, which is necessary to improve the clinical protocol and further apply successfully this therapy in SSc patients.

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