Evaluation of thymic function after autologous hematopoietic stem cell transplantation in systemic sclerosis patients

• Grant number: 14/20922-2
• Support type: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): January 01, 2015
• Effective date (End): December 18, 2015
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal researcher: Eduardo Antônio Donadi
• Grantee: Lucas Coelho Marlière Arruda
• Supervisor abroad: Dominique Farge
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: Hôpital Saint-Louis, France
• Associated to the scholarship: 13/18678-3 - Study of immunological mechanisms involved in the therapeutic response of patients with systemic sclerosis to autologous hematopoietic stem cells transplantation, BP.DR

Abstract

Systemic sclerosis (SSc) is a chronic connective tissue disease, characterized by microvascular lesions associated with different degrees of skin and internal organ fibrosis. The etiology of SSc remains unknown and mechanisms involved in the pathogenesis are not completely understood. Moreover, treatments available have limited efficacy in controlling disease progression. Currently, autologous hematopoietic stem cell transplantation (AHSCT) is a promising therapeutic alternative for severe forms of SSc, restraining progression and/or enabling disease control with conventional treatment in previously refractory patients. The generation of a new and diverse TCR ("T-cell receptor") repertoire has been reported as a mechanism of action of AHSCT for autoimmune diseases, indicating that post-transplantation de novo generation of a new, more diverse and self-tolerant immunological system is associated with clinical remission. The goal of this project is to evaluate the influence of thymus reactivation in 25 SSc patients' clinical response after AHSCT. We will evaluate the changes in TCR repertoire diversity by TCRBV CDR3 Spectratyping and absolute levels of signal joint T-cell receptor excision circles (sjTREC) and beta-TREC by RT-qPCR after transplantation from baseline until at least two years post-AHSCT, correlating the results with the clinical outcomes. This study will help to clarify the immunological mechanisms involved with the AHSCT therapy, what is necessary to improve the clinical protocol and further application of this therapy to treat SSc patients. (AU)

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)

ARRUDA, LUCAS C. M.; LIMA-JUNIOR, JOAO R.; CLAVE, EMMANUEL; MORAES, DANIELA A.; DOUAY, CORINNE; FOURNIER, ISABELLE; MOINS-TEISSERENC, HELENE; COVAS, DIMAS T.; SIMOES, BELINDA P.; FARGE, DOMINIQUE; TOUBERT, ANTOINE; MALMEGRIM, KELEN C. R.; OLIVEIRA, MARIA CAROLINA. Homeostatic proliferation leads to telomere attrition and increased PD-1 expression after autologous hematopoietic SCT for systemic sclerosis. BONE MARROW TRANSPLANTATION, v. 53, n. 10, p. 1319-1327, OCT 2018. Web of Science Citations: 5.

ARRUDA, LUCAS C. M.; MALMEGRIM, KELEN C. R.; LIMA-JUNIOR, JOAO R.; CLAVE, EMMANUEL; DIAS, JULIANA B. E.; MORAES, DANIELA A.; DOUAY, CORINNE; FOURNIER, ISABELLE; MOINS-TEISSERENC, HELENE; ALBERDI, ANTONIO JOSE; COVAS, DIMAS T.; SIMOES, BELINDA P.; LANSIAUX, PAULINE; TOUBERT, ANTOINE; OLIVEIRA, MARIA CAROLINA. Immune rebound associates with a favorable clinical response to autologous HSCT in systemic sclerosis patients. BLOOD ADVANCES, v. 2, n. 2, p. 126-141, JAN 23 2018. Web of Science Citations: 15.

ARRUDA, L. C. M.; CLAVE, E.; MOINS-TEISSERENC, H.; DOUAY, C.; FARGE, D.; TOUBERT, A. Resetting the immune response after autologous hematopoietic stem cell transplantation for autoimmune diseases. CURRENT RESEARCH IN TRANSLATIONAL MEDICINE, v. 64, n. 2, p. 107-113, APR-JUN 2016. Web of Science Citations: 11.