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THU0501 Hematopoietic Stem Cell Transplantation Increases Naive and Regulatory B Cells While Decreasing Memory B Cells in Systemic Sclerosis Patients
  1. L.C.M. Arruda1,2,
  2. M.C. Oliveira3,
  3. D.A. Moraes3,
  4. D.T. Covas2,3,
  5. J.C. Voltarelli2,3,
  6. K.C.R. Malmegrim2,4
  1. 1Biochemistry and Immunology, Ribeirão Preto Medical School
  2. 2National Institute of Science and Technology in Stem Cells and Cell Therapy
  3. 3Department of Clinical Medicine, Ribeirão Preto Medical School
  4. 4Department of Clinical, Toxicological and Bromatological Analysis, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil

Abstract

Background High dose immunossuppression (HDI) followed by autologous hematopoietic stem cell transplantation (AHSCT) emerged in last past years as a therapeutic alternative for systemic sclerosis (SSc) patients [1]. The evaluation of immune reconstitution is important to elucidate the therapeutic mechanisms and improve treatment efficacy [2, 3].

Objectives To address immune reconstitution dynamics after HDI/AHSCT through quantification of regulatory T and B cells, suppressor T cells, naive and memory B cells.

Methods Peripheral blood was collected from 15 diffuse SSc patients before and 6 and 12 months after transplantation. Peripheral blood mononuclear cells were immunophenotyped by flow cytometry.

Results Numbers of regulatory B cells (CD19+CD24hiCD38hi) were significantly increased at 6 and 12 months post-AHSCT, compared with baseline, despite no alterations in CD4+CD25hiFoxP3+ regulatory T cell numbers. Absolute counts of CD8+CD28CD57+ suppressor T cells were also significantly increased at 6 and 12 months post-therapy, when compared with the pre-treatment period. Simultaneously, numbers of CD19+CD27+IgD memory B cells were significantly decreased at 6 and 12 months, while CD19+CD27+IgD+ naive B cells transiently increased at 6 months, when compared with baseline.

Conclusions Our results suggest improvement of peripheral immunoregulatory mechanisms and ablation of memory B cells after HDI/AHSCT, which may contribute to reestablishment of self-tolerance and control of autoimmunity in SSc patients.

References

  1. Farge D, Labopin M, Tyndall A, Fassas A, Mancardi GL, Van Laar J, et al. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years' experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases. Haematologica. 2010 Feb; 95(2):284-292.

  2. Farge D, Henegar C, Carmagnat M, Daneshpouy M, Marjanovic Z, Rabian C, et al. Analysis of immune reconstitution after autologous bone marrow transplantation in systemic sclerosis. Arthritis Rheum. 2005 May; 52(5):1555-1563.

  3. Tsukamoto H, Nagafuji K, Horiuchi T, Mitoma H, Niiro H, Arinobu Y, et al. Analysis of immune reconstitution after autologous CD34+ stem/progenitor cell transplantation for systemic sclerosis: predominant reconstitution of Th1 CD4+ T cells. Rheumatology (Oxford). 2011 May; 50(5):944-952.

Acknowledgements Funding for this project was provided by CNPq and FAPESP.

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.4148

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