Cytomegalovirus shapes long-term immune reconstitution after allogeneic stem cell transplantation

被引:38
作者
Itzykson, Raphael [1 ,2 ]
Robin, Marie [1 ]
Moins-Teisserenc, Helene [2 ,3 ,4 ]
Delord, Marc [2 ,5 ]
Busson, Marc [3 ,4 ]
Xhaard, Alienor [1 ]
de Fontebrune, Flore Sicre [1 ,2 ]
de latour, Regis Peffault [1 ]
Toubert, Antoine [2 ,3 ,4 ]
Socie, Gerard [1 ,2 ,4 ]
机构
[1] Hop St Louis, AP HP, Serv Hematol Greffe, Paris, France
[2] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France
[3] Hop St Louis, AP HP, Immunol Lab, Paris, France
[4] Inst Univ Hematol, Inserm UMRS 1160, Paris, France
[5] Inst Univ Hematol, Plateforme Bioinformat & Biostat, Paris, France
关键词
BONE-MARROW-TRANSPLANTATION; T-CELL; IMMUNOLOGICAL RECONSTITUTION; IMPACT; REACTIVATION; RECOVERY; BURDEN;
D O I
10.3324/haematol.2014.113415
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:114 / 123
页数:10
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