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Evolution of serum cytokine profile after hematopoietic stem cell transplantation in systemic sclerosis patients

Bone Marrow Transplantation volume 51, pages 1146–1149 (2016)Cite this article

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Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by auto-Ab production and predominant T-cell infiltration, resulting in excessive fibrosis within the skin and internal organs.1 The various cytokines and chemokines produced by the activated T cells contribute to recruiting additional inflammatory cells and to fibroblast activation, which promote extracellular matrix production and fibrosis.1 SSc has been related to a Th1/Th2 dysregulation, with increase in tissue expression and in circulating Th2 cytokine levels, namely interleukin (IL)-4, IL-13 and IL-10.2 Increased serum levels of IL-2, IL-6, TNF-α, IL-8 and monocyte chemoattractant protein (MCP)-1 were also found in SSc patients.2, 3, 4 Although transforming growth factor (TGF)-β is one of the key mediators of increased collagen synthesis, TGF-β plasma levels did not appear to be increased in SSc patients.4 Among the endothelial markers analyzed in SSc patients, serum levels of E-selectin and P-selectin,5 as well as of vascular endothelial growth factor (VEGF) and of PDGF6 were found to be increased. Therefore, the question remains if monitoring patients’ serum cytokine profiles could be of help during routine clinical follow-up.

Over the past 20 years, autologous hematopoietic stem cell transplantation (aHSCT) has emerged as a new effective therapy for severe rapidly progressive diffuse cutaneous SSc (dcSSc). The early phase II studies showed that aHSCT allowed regression of skin and lung fibrosis.7 Then, the European Society for Blood and Marrow Transplantation (EBMT)–European League Against Rheumatism (EULAR)-randomized Autologous Stem cell Transplantation International Scleroderma (ASTIS) trial demonstrated that aHSCT conferred significant long-term overall and event-free survival benefit in dSSc patients when compared with cyclophosphamide conventional therapy.8 After aHSCT, the immune reconstitution process in SSc patients is characterized by the reemergence of naive B cells and T cells, and resetting of the immune system,9 with progressive increases in the regulatory T-cell numbers10 and in Th1/Th2 cell ratio.11

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Acknowledgements

This work was supported by Groupe Francophone de Recherche sur la Sclérodermie (GFRS), Association des Sclérodermiques de France (ASF), INSERM, Agence Nationale pour la Recherche, the Délégation Régionale à la Recherche Clinique (DRRC) from the Assistance Publique-Hôpitaux de Paris (AP-HP), the French Ministry of Health (PHRC 1997 AOM 6597–030) and the Etablissement Français des Greffes. In memoriam of Dr Homa KESHTMAND (Department of Internal Medicine, Hôpital Saint-Louis), for a sustained and dedicated work over 15 years at St Louis Hospital, who contributed to patients follow-up and blood samples collection.

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Author notes

  1. L Michel and D Farge: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, INSERM U976, Skin Research Institute, Hôpital Saint-Louis, Paris, France

    L Michel, J Baraut, F Jean-Louis & E I Grigore

  2. Unité Clinique de Médecine Interne, Maladies Autoimmunes et Pathologie Vasculaire, UF 04, Hôpital Saint-Louis, AP-HP Assistance Publique des Hôpitaux de Paris, INSERM UMRS 1160, Paris Denis Diderot University, Paris, France

    D Farge, Z Marjanovic & C Deligny

  3. Department of Biostatistics, Hôpital Saint-Louis, Paris, France

    R Porcher

  4. CKCL, Leiden University Medical Centre, Leiden, Netherlands

    F Romijn, J van Pelt & J M van Laar

  5. Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

    L C M Arruda

  6. Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

    L C M Arruda

  7. Department of Rheumatology, Leiden University Medical Centre, Leiden, Netherlands

    N Levarht

  8. INSERM UMRs 957, Nantes University, Nantes, France

    F Verrecchia

  9. Institute of Cellular Medicine, Newcastle University, Newcastle, UK

    J M van Laar

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  1. L Michel
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Correspondence to L Michel or D Farge.

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Michel, L., Farge, D., Baraut, J. et al. Evolution of serum cytokine profile after hematopoietic stem cell transplantation in systemic sclerosis patients. Bone Marrow Transplant 51, 1146–1149 (2016). https://doi.org/10.1038/bmt.2016.77

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