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Analysis of the immune determinants of the observed clinical response after treatment by allogeneic Mensenchymal Stem Cell (MSC) in Systemic Sclerosis (SSc) patients – Interactions between MSC and B cells

1,2 S. Loisel, 3,4 P.Lansiaux, 1,2 C. Ménard, 1,2 K.Tarte, 3,4 D. Farge

 1 SITI Laboratory, Etablissement Français du Sang Bretagne, CHU Rennes, France

2 UMR U1236, INSERM, Université Rennes 1, Rennes, France

3 Hôpital Saint-Louis, Centre de Référence Maladies systémiques rares d’Iles de France, Paris, France

4 Institut Universitaire d’Hématologie, EA 3518, Paris, France

Introduction:

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by vasculopathy, activation of the immune response and consequent fibrosis. Mesenchymal stem cells (MSC) are studied as a new cell therapy for SSc due to their immunosuppressive effects on the various components of the immune response, including B cells which role in SSc physiopathology was recently emphasized.

Cellules souches mésenchymateuse

Objectives:  

To analyse the immunomodulation effect of Bone-Marrow (BM) derived allogeneic-MSC in 12 SSc patients iv treated (AOM11250 PHRC protocol (DRCI, APHP)), as focused on MSC and B cells interaction, in order to investigate if MSC treatment : a)  modify B cells subpopulations b) inscrease circulating Breg numbers and c) changes B cell functionality (assessed by gene expression analysis).

Materiel and Methods:

The research involves peripheral blood cells and serum samples biobanking obtained from 12 SSc patients before, 1 and 3 months after BM allo-MSC injection. B cell subpopulations analysis and Breg enrichment evaluation are performed through Flow cytometry. Gene expression quantification is evaluated by Biomark analysis of 62 target genes involved in B cell functionality.

Results:

Transitional B cell compartment (CD24hi CD38hi CD27), known to have regulatory properties tends to increase after MSC treatment (n=12). Analysis of IL-10-producing-Breg enrichment is currently in progress. Total B cell gene expression analysis after MSC treatment shows: 1) a slight transitional increase in IL-10 mRNA 2) a slight transitional decrease in CD5, BANK-1 et CD40 mRNAs, 3) stable TGF-B et BLIMP-1 mRNAs level. Isolation of B-cells subpopulations and single cell analysis are currently under progress to identify which B-cell may account for potential modulation of B-cell gene expression.

Conclusion: The observed results are expected  to generate new tools to evaluate human circulating B reg cells and to enhance the understanding of SSc pathogenesis and the early promising results from this highly innovative therapy.

Caractérisation phénotypique et fonctionnelle des sous-populations lymphocytaires B dans la sclérodermie systémique.

*Ce projet de recherche bénéficie d’une bourse  de recherche du GFRS 2014

Par Alexandra Forestier1,2,3,4, Thomas Guerrier1,4, Sylvain Dubucquoi1,4, Ibrahim Yacoub-Agha1,4,5, Myriam Labalette1,4, David Launay1,2,3,4

1. Université de Lille, UFR Médecine, F-59000 Lille, France
2. CHRU Lille, Pôle Spécialités Médicales et Gérontologie, Département de Médecine Interne et Immunologie Clinique, F-59037 Lille Cedex, France
3. Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), F-59037 Lille Cedex, France
4. EA2686, LIRIC, F-59000 Lille, France
5. CHRU Lille, Service des Maladies du Sang, F-59037 Lille Cedex, France

La sclérodermie systémique (SSc) est une maladie invalidante marquée par une fibrose cutanée et systémique sévère, dont la physiopathologie implique une activation des fibroblastes, des cellules endothéliales et du système immunitaire cellulaire et humoral (Fig. 1). Elle constitue un modèle d’étude des processus fibrosants et des liens entre fibrose et immunité. Lire la suite…