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Functional and immunophenotypical assessment of T helper lymphocyte subpopulations in systemic sclerosis patients treated with autologous hematopoietic stem cell transplantation

Grant number: 22/02137-2
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2023
Effective date (End): December 31, 2024
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Maria Carolina de Oliveira Rodrigues
Grantee:Maynara Santana Gonçalves
Host Institution: Hemocentro de Ribeirão Preto. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil

Abstract

Systemic sclerosis is an autoimmune disease characterized by microvasculopathy, immune dysregulation and excessive production of collagen, resulting fibrosis of the skin and internal organs. The etiology of SSc remains unknown, and treatment is organ-directed, based on the extent and severity of lesions. The efficacy of conventional therapeutic strategies for SSc is limited, especially in severe cases. Autologous Hematopoietic Stem Cell Transplantation (AHSCT) promotes resetting of the immune system and has emerged as a treatment option for patients with severe and progressive SSc. Although most patients improve clinically and remain in remission for long-term, approximately 20% reactivate the baseline autoimmune disease. The triggers and factors associated with these reactivations are not fully understood and little has been explored about the immunological profile of patients that reactivate the disease in comparison to those that remain in remission. Thus, the aim of the present study is to evaluate the immunological profile and function of subpopulations of CD4+ T cells and their association in the therapeutic response of patients with SSc after AHSCT, including: i) immunophenotyping of subpopulations of CD4+ T cells in peripheral blood, ii) in vitro production of cytokines by CD4+T cells, iii) ability to suppress regulatory T cells, iv) quantification of serum cytokine levels, v) expression of cytokines and lymphocyte migration receptors in patients' skin biopsies, vi) correlation of immunological and laboratory parameters with the clinical response of the patients. The findings may reveal prognostic/response biomarkers after transplantation, identifying immunological patterns associated with better or worse clinical response. Our hypothesis is that a more regulatory immunological profile is associated with a better prognosis and remission of the disease after transplantation. Thus, the study will contribute to clarifying immunological mechanisms of transplant efficacy, improving clinical protocols and possibly enabling the use of additional therapeutic approaches.Key Words: Systemic sclerosis, hematopoietic stem cell transplantation, immune monitoring, helper T cells, immunoregulation, prognostic biomarkers.

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