title: Autologous haematopoietic stem cell transplantation reduces abnormalities in the expression of immune genes in multiple sclerosis.
abstract: Autologous haematopoietic stem-cell transplantation (AHSCT) has been experimented as a treatment in patients affected by severe forms of multiple sclerosis (MS) who failed to respond to standard immunotherapy. The rationale of AHSCT is to 'reboot' the immune system and reconstitute a new adaptive immunity. The aim of our study was to identify, through a robust and unbiased transcriptomic analysis, any changes of gene expression in T-cells potentially underlying the treatment effect in patients who underwent non-myeloablative AHSCT for treatment of MS. We evaluated by microarray DNA-chip technology the gene expression of peripheral CD4+ and CD8+ T-cell subsets sorted from patients with MS patients before AHSCT, at 6 months, 1 year and 2 years after AHSCT and from healthy control subjects. Hierarchical clustering analysis revealed that reconstituted CD8+ T-cells of MS patients at 2 years post-transplantation, aggregated together with healthy controls, suggesting a normalization of gene expression in CD8+ cells post-therapy. When we compared the gene expression in MS patients before and after therapy, we detected a large number of differentially expressed genes (DEG) in both CD8+ and CD4+ T-cell subsets at all time points after transplantation. We catalogued the biological function of DEG and we selected 27 genes known to be involved in immune function for accurate quantification of gene expression by real-time PCR. The analysis confirmed and extended with quantitative data, a number of significant changes in both the CD4+ and CD8+ T-cells subsets from MS post-transplant. Notably, CD8+ T-cells revealed more extensive changes in the expression of genes involved in effector immune responses.
authors.forename: Alessandra
authors.initials: A
authors.lastname: de Paula A Sousa
authors.affiliation: ‡Department of Clinical, Toxicological and Bromatological Analysis, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Kelen C R
authors.initials: KC
authors.lastname: Malmegrim
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Panepucci
authors.affiliation: ∥Department of Neuroscience and Behavioral Science, Hospital das Clinicas, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Doralina S
authors.initials: DS
authors.lastname: Brum
authors.affiliation: ∥Department of Neuroscience and Behavioral Science, Hospital das Clinicas, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Amilton A
authors.initials: AA
authors.lastname: Barreira
authors.affiliation: ∥Department of Neuroscience and Behavioral Science, Hospital das Clinicas, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Antonio
authors.initials: A
authors.lastname: Carlos Dos Santos
authors.affiliation: §Division of Hematology, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Amélia G
authors.initials: AG
authors.lastname: Araújo
authors.affiliation: †National Institute of Science and Technology in Stem Cell and Cell Therapy (INCTC), Regional Blood Center, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Dimas Tadeu
authors.initials: DT
authors.lastname: Covas
authors.affiliation: ¶Blood and Marrow Transplant Unit, Hospital das Clinicas, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Oliveira
authors.affiliation: ¶Blood and Marrow Transplant Unit, Hospital das Clinicas, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Moraes
authors.affiliation: ¶Blood and Marrow Transplant Unit, Hospital das Clinicas, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Fabiano
authors.initials: F
authors.lastname: Pieroni
authors.affiliation: ¶Blood and Marrow Transplant Unit, Hospital das Clinicas, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: George M
authors.initials: GM
authors.lastname: Barros
authors.affiliation: ¶Blood and Marrow Transplant Unit, Hospital das Clinicas, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Belinda P
authors.initials: BP
authors.lastname: Simões
authors.affiliation: **Imperial College Healthcare NHS Trust, London, U.K.
authors.forename: Richard
authors.initials: R
authors.lastname: Nicholas
authors.affiliation: ††Division of Immunotherapy, Northwestern University, Chicago, IL, U.S.A.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Burt
authors.forename: Júlio C
authors.initials: JC
authors.lastname: Voltarelli
authors.affiliation: *Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, U.K.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Muraro
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000328:Adult; D015496:CD4-Positive T-Lymphocytes; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000628:therapy*