Immune rebound associates with a favorable clinical response to autologous HSCT in systemic sclerosis patients

Author(s):Show less -

Arruda, Lucas C. M. ^{[1, 2]} ; Malmegrim, Kelen C. R. ^{[1, 3]} ; Lima-Junior, Joao R. ^{[1, 4]} ; Clave, Emmanuel ^{[5, 6]} ; Dias, Juliana B. E. ^[7] ; Moraes, Daniela A. ^[7] ; Douay, Corinne ^[6] ; Fournier, Isabelle ^[6] ; Moins-Teisserenc, Helene ^{[5, 6]} ; Alberdi, Antonio Jose ^{[5, 8]} ; Covas, Dimas T. ^{[7, 1]} ; Simoes, Belinda P. ^{[7, 1]} ; Lansiaux, Pauline ^[9] ; Toubert, Antoine ^{[5, 6]} ; Oliveira, Maria Carolina ^{[7, 1, 2]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Reg Hemotherapy Ctr, Ctr Cell Based Therapy, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Basic & Appl Immunol Program, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Toxicol & Bromatol Anal, Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Grad Program Biosci Appl Pharm, Ribeirao Preto - Brazil

^[5] Univ Paris Diderot, Sorbonne Paris Cite, Inst Univ Hematol, Paris - France

^[6] Hop St Louis, AP HP, Inst Univ Hematol, INSERM, Unite Mixte Rech 1160, Paris - France

^[7] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Ribeirao Preto - Brazil

^[8] Inst Univ Hematol, Plateforme Technol, Paris - France

^[9] Hop St Louis, AP HP, Ctr Reference Malad Autoimmune Syst Rares Ile de, FAI2R, UF 04, Unite Med Interne Malad Autoimmunes &, Paris - France

• Document type: Journal article
• Source: BLOOD ADVANCES; v. 2, n. 2, p. 126-141, JAN 23 2018.
• Web of Science Citations: 15

Abstract

To evaluate the immunological mechanisms associated with clinical outcomes after autologous hematopoietic stem cell transplantation (AHSCT), focusing on regulatory T- (Treg) and B- (Breg) cell immune reconstitution, 31 systemic sclerosis (SSc) patients underwent simultaneous clinical and immunological evaluations over 36-month posttransplantation follow-up. Patients were retrospectively grouped into responders (n = 25) and nonresponders (n = 6), according to clinical response after AHSCT. Thymic function and B-cell neogenesis were respectively assessed by quantification of DNA excision circles generated during T- and B-cell receptor rearrangements. At the 1-year post-AHSCT evaluation of the total set of transplanted SSc patients, thymic rebound led to renewal of the immune system, with higher T-cell receptor (TCR) diversity, positive correlation between recent thymic emigrant and Treg counts, and higher expression of CTLA-4 and GITR on Tregs, when compared with pretransplant levels. In parallel, increased bone marrow output of newly generated naive B-cells, starting at 6 months after AHSCT, renovated the B-cell populations in peripheral blood. At 6 and 12 months after AHSCT, Bregs increased and produced higher interleukin-10 levels than before transplant. When the nonresponder patients were evaluated separately, Treg and Breg counts did not increase after AHSCT, and high TCR repertoire overlap between pre- and posttransplant periods indicated maintenance of underlying disease mechanisms. These data suggest that clinical improvement of SSc patients is related to increased counts of newly generated Tregs and Bregs after AHSCT as a result of coordinated thymic and bone marrow rebound. (AU)

• FAPESP's process: 14/20922-2 - Evaluation of thymic function after autologous hematopoietic stem cell transplantation in systemic sclerosis patients
• Grantee: Lucas Coelho Marlière Arruda
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 13/18678-3 - Study of immunological mechanisms involved in the therapeutic response of patients with systemic sclerosis to autologous hematopoietic stem cells transplantation
• Grantee: Lucas Coelho Marlière Arruda
• Support Opportunities: Scholarships in Brazil - Doctorate