title: Cytomegalovirus shapes long-term immune reconstitution after allogeneic stem cell transplantation.
abstract: Immune reconstitution after allogeneic stem cell transplantation is a dynamic and complex process depending on the recipient and donor characteristics, on the modalities of transplantation, and on the occurrence of graft-versus-host disease. Multivariate methods widely used for gene expression profiling can simultaneously analyze the patterns of a great number of biological variables on a heterogeneous set of patients. Here we use these methods on flow cytometry assessment of up to 25 lymphocyte populations to analyze the global pattern of long-term immune reconstitution after transplantation. Immune patterns were most distinct from healthy controls at six months, and had not yet fully recovered as long as two years after transplant. The two principal determinants of variability were linked to the balance of B and CD8(+) T cells and of natural killer and B cells, respectively. Recipient's cytomegalovirus serostatus, cytomegalovirus replication, and chronic graft-versus-host disease were the main factors shaping the immune pattern one year after transplant. We identified a complex signature of under- and over-representation of immune populations dictated by recipient's cytomegalovirus seropositivity. Finally, we identified dimensions of variance in immune patterns as significant predictors of long-term non-relapse mortality, independently of chronic graft-versus-host disease.
authors.affiliation: Service d'Hématologie Greffe, Hôpital Saint-Louis, APHP, Paris Université Paris-Diderot et Paris Sorbonne Cité
authors.forename: Raphael
authors.initials: R
authors.lastname: Itzykson
authors.affiliation: Service d'Hématologie Greffe, Hôpital Saint-Louis, APHP, Paris.
authors.forename: Marie
authors.initials: M
authors.lastname: Robin
authors.affiliation: Université Paris-Diderot et Paris Sorbonne Cité Laboratoire d'Immunologie, Hôpital Saint-Louis, APHP, Paris Inserm UMRS-1160, Institut Universitaire d'Hématologie, Paris.
authors.forename: Helene
authors.initials: H
authors.lastname: Moins-Teisserenc
authors.affiliation: Université Paris-Diderot et Paris Sorbonne Cité Plateforme de Bioinformatique et Biostatistique, Institut Universitaire d'Hématologie, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Delord
authors.affiliation: Laboratoire d'Immunologie, Hôpital Saint-Louis, APHP, Paris Inserm UMRS-1160, Institut Universitaire d'Hématologie, Paris.
authors.forename: Marc
authors.initials: M
authors.lastname: Busson
authors.affiliation: Service d'Hématologie Greffe, Hôpital Saint-Louis, APHP, Paris.
authors.forename: Aliénor
authors.initials: A
authors.lastname: Xhaard
authors.affiliation: Service d'Hématologie Greffe, Hôpital Saint-Louis, APHP, Paris Université Paris-Diderot et Paris Sorbonne Cité
authors.forename: Flore Sicre
authors.initials: FS
authors.lastname: de Fontebrune
authors.affiliation: Service d'Hématologie Greffe, Hôpital Saint-Louis, APHP, Paris.
authors.forename: Régis
authors.initials: R
authors.lastname: Peffault de Latour
authors.affiliation: Université Paris-Diderot et Paris Sorbonne Cité Laboratoire d'Immunologie, Hôpital Saint-Louis, APHP, Paris Inserm UMRS-1160, Institut Universitaire d'Hématologie, Paris.
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
authors.affiliation: Service d'Hématologie Greffe, Hôpital Saint-Louis, APHP, Paris Université Paris-Diderot et Paris Sorbonne Cité Inserm UMRS-1160, Institut Universitaire d'Hématologie, Paris gerard.socie@paris7.jussieu.fr.
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D020127:Recovery of Function / Q000276:immunology*; D014181:Transplantation Immunology / Q000276:immunology*; D014184:Transplantation, Homologous