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

Lucas C.M. Arruda; Kelen C.R. Malmegrim; João R. Lima-Júnior; Emmanuel Clave; Juliana B.E. Dias; Daniela A. Moraes; Corinne Douay; Isabelle Fournier; Hélène Moins-Teisserenc; Antônio José Alberdi; Dimas T. Covas; Belinda P. Simões; Pauline Lansiaux; Antoine Toubert; Maria Carolina Oliveira

Blood Advances (Jan 2018)

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

Lucas C.M. Arruda,
Kelen C.R. Malmegrim,
João R. Lima-Júnior,
Emmanuel Clave,
Juliana B.E. Dias,
Daniela A. Moraes,
Corinne Douay,
Isabelle Fournier,
Hélène Moins-Teisserenc,
Antônio José Alberdi,
Dimas T. Covas,
Belinda P. Simões,
Pauline Lansiaux,
Antoine Toubert,
Maria Carolina Oliveira

Affiliations

Lucas C.M. Arruda: Basic and Applied Immunology Program, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil;; Center for Cell-based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil;
Kelen C.R. Malmegrim: Center for Cell-based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil;; Department of Clinical, Toxicological and Bromatological Analysis, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil;
João R. Lima-Júnior: Center for Cell-based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil;; Graduate Program on Bioscience Applied to Pharmacy, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil;
Emmanuel Clave: INSERM Unité Mixte de Recherche 1160, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris, France;; Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France;
Juliana B.E. Dias: Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil;
Daniela A. Moraes: Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil;
Corinne Douay: INSERM Unité Mixte de Recherche 1160, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris, France;
Isabelle Fournier: INSERM Unité Mixte de Recherche 1160, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris, France;
Hélène Moins-Teisserenc: INSERM Unité Mixte de Recherche 1160, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris, France;; Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France;
Antônio José Alberdi: Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France;; Plateforme Technologique, Institut Universitaire d'Hématologie, Paris, France;
Dimas T. Covas: Center for Cell-based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil;; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil;
Belinda P. Simões: Center for Cell-based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil;; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil;
Pauline Lansiaux: Unité de Médecine Interne, Maladies Autoimmunes et Pathologie Vasculaire, UF 04, AP-HP, Centre de référence des maladies auto-immunes systémiques rares d'Ile-de-France (site constitutif), FAI2R, Hôpital Saint-Louis, Paris, France
Antoine Toubert: INSERM Unité Mixte de Recherche 1160, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris, France;; Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France;; Antoine Toubert, Laboratoire Alloimmunité, Autoimmunité, Transplantation, Hôpital Saint-Louis, Université Paris Diderot, Sorbonne Paris Cité, INSERM UMR-1160, Institut Universitaire d'Hématologie, 1 Ave Claude Vellefaux, 75010 Paris, France
Maria Carolina Oliveira: Basic and Applied Immunology Program, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil;; Center for Cell-based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil;; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil;; Maria Carolina Oliveira, Divisão de Imunologia Clínica, Departamento de Clínica Médica, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Avenida dos Bandeirantes 3900, Ribeirão Preto, São Paulo 14048-900, Brazil;

Journal volume & issue: Vol. 2, no. 2
pp. 126 – 141

Abstract

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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.

Published in Blood Advances

ISSN: 2473-9529 (Print); 2473-9537 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine
Website: https://ashpublications.org/bloodadvances

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