Immunological correlates of favorable long-term clinical outcome in multiple sclerosis patients after autologous hematopoietic stem cell transplantation.
High dose immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) induces prolonged clinical remission in multiple sclerosis (MS) patients. However, how patient immune profiles are associated with clinical outcomes has not yet been completely elucidated. In this study, 37 MS patients were assessed for neurological outcomes, thymic function and long-term immune reconstitution after AHSCT. Patients were followed for a mean (SD) of 68.5 (13.9) months post-transplantation and were retrospectively clustered into progression- and non-progression groups, based on Expanded Disease Status Scale (EDSS) outcomes at last visit. After AHSCT, both patient groups presented increased regulatory T-cell subset counts, early expansion of central- and effector-memory CD8(+)T-cells and late thymic reactivation. However, the non-progression group presented early expansion of PD-1(+)CD8(+)T-cells and of PD-1-expressing CD19(+) B-cells. Here, we suggest that along with increased numbers of regulatory T-cell subsets, PD-1 inhibitory signaling is one possible immunoregulatory mechanism by which AHSCT restores immune tolerance in MS patients.
Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Lucas C M
LCM
Arruda
Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Júlia T C
JTC
de Azevedo
Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Gislane L V
GLV
de Oliveira
Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Gabriela T
GT
Scortegagna
Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Evandra S
ES
Rodrigues
Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Patrícia V B
PVB
Palma
Department of Neuroscience and Behavioral Science, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Neurology, Psychology and Psychiatry, School of Medicine of Botucatu, Universidade Estadual Paulista, UNESP, Botucatu, Brazil.
Doralina G
DG
Brum
Department of Neuroscience and Behavioral Science, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Carlos T
CT
Guerreiro
Department of Neuroscience and Behavioral Science, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Vanessa D
VD
Marques
Department of Neuroscience and Behavioral Science, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Amilton A
AA
Barreira
Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Dimas T
DT
Covas
Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Belinda P
BP
Simões
Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Júlio C
JC
Voltarelli
Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Maria Carolina
MC
Oliveira
Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Clinical, Toxicological and Bromatological Analysis, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. Electronic address: kelenfarias@fcfrp.usp.br.
Kelen C R
KCR
Malmegrim
D000328:Adult; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology / Q000628:therapy*; D017063:Outcome Assessment, Health Care; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism; D012189:Retrospective Studies; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology*; D013997:Time Factors; D014182:Transplantation, Autologous; D055815:Young Adult
D018941:Antigens, CD19; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
Hematopoietic stem cell transplantation; Immune reconstitution; Immunoregulation; Multiple sclerosis; PD-1; Regulatory T-cells