CD45RA depletion in HLA-mismatched allogeneic hematopoietic stem cell transplantation for primary combined immunodeficiency: A preliminary study Fabien.

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Presentation transcript:

CD45RA depletion in HLA-mismatched allogeneic hematopoietic stem cell transplantation for primary combined immunodeficiency: A preliminary study Fabien Touzot, MD, PhD, Bénédicte Neven, MD, PhD, Liliane Dal-Cortivo, MD, Aurélie Gabrion, MSc, Despina Moshous, MD, PhD, Guilhem Cros, MD, Maryline Chomton, MD, Jean-Marc Luby, PGDipMLSc, Brigitte Terniaux, PGDipMLSc, Jérémy Magalon, PharmD, MSc, Capucine Picard, MD, PhD, Stéphane Blanche, MD, Alain Fischer, MD, PhD, Marina Cavazzana, MD, PhD Journal of Allergy and Clinical Immunology Volume 135, Issue 5, Pages 1303-1309.e3 (May 2015) DOI: 10.1016/j.jaci.2014.08.019 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Scheme of the CD45RA depletion process. The BM sample undergoes 2 selection steps. First, in vitro T-lymphocyte depletion of BM was performed with a CD34+ immunomagnetic CliniMACS system (Miltenyi Biotec). The negative fraction was then CD45RA+ depleted with a CD45RA CliniMACS kit. The final cell therapy product consists of the CD34+ and CD34−CD45RA− negative fractions. Journal of Allergy and Clinical Immunology 2015 135, 1303-1309.e3DOI: (10.1016/j.jaci.2014.08.019) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 T-cell reconstitution after HSCT with a CD45RA-depleted allograft (patients P2, P3, and P5). A, Absolute CD3+ lymphocyte counts in peripheral blood of patients at 3, 6, 9, and 12 months and at last follow-up. B, Absolute CD3+CD4+ lymphocyte counts in peripheral blood of patients at 3, 6, 9, and 12 months and at last follow-up. C, Absolute CD3+CD8+ lymphocyte counts in peripheral blood of patients at 3, 6, 9, and 12 months and at last follow-up. D, Percentage of CD3+CD4+ lymphocytes expressing CD45RA and the CD31 markers in peripheral blood of patients treated with a CD45RA-depleted allografts at 6, 9, and 12 months and at last follow-up. E, Percentage of CD3+CD8+ lymphocyte subsets in patients at 6, 9, and 12 months and at last follow-up. Subsets were determined according to their expression of CCR7 and CD45RA, as follows: naive cells (CCR7+CD45RA+), effector memory cells (CCR7−CD45RA−), central memory cells (CCR7+CD45RA−), and TEMRA cells (CCR7−CD45RA+). Journal of Allergy and Clinical Immunology 2015 135, 1303-1309.e3DOI: (10.1016/j.jaci.2014.08.019) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 B and natural killer (NK) cell reconstitution after HSCT with CD45RA depletion. A, Absolute CD19+ lymphocyte counts in peripheral blood of patients at 3, 6, 9, and 12 months and at last follow-up. B, Absolute CD3−CD16+CD56+ lymphocyte counts in peripheral blood of patients at 3, 6, 9 and 12 months and at last follow-up. Journal of Allergy and Clinical Immunology 2015 135, 1303-1309.e3DOI: (10.1016/j.jaci.2014.08.019) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 CMV-specific T-cell responses in patients treated with CD45RA-depleted HSCT. A, Detection of CMV-specific CD8+ T cells in patient P1 by using pentamers restricted to MHC HLA-A2 and the pp65 antigen before and after HSCT (days +10 and +37, upper panel). Detection of CMV-specific CD8+ T cells in patient P1 by using IFN-γ staining of CD8+ lymphocytes incubated in vitro with the Peptivator pp65 antigen before and after HSCT (days +10 and +37, lower panel) is also shown. Patient P1 received a DLI at day +36. B, Detection of CMV-specific CD8+ T cells in patient P3 by using pentamers restricted to MHC HLA-A1 and the p50 antigen before and after HSCT (days +21 and +39). Phenotypic analysis of CMV-specific CD8+ T cells according to CD62 ligand (CD62L) and CD45RA before and after HSCT (day +39) is also shown. Journal of Allergy and Clinical Immunology 2015 135, 1303-1309.e3DOI: (10.1016/j.jaci.2014.08.019) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 CD45RA depletion of the allograft maintains the presence of CMV-specific CD8+ T cells. CMV-specific CD8+ T cells are detected in the CD34− fraction and the CD45RA-depleted allograft at a similar frequency by using pentamers specific for HLA-A1 and the CMV p50 antigen (patient P1). Journal of Allergy and Clinical Immunology 2015 135, 1303-1309.e3DOI: (10.1016/j.jaci.2014.08.019) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions