Molecular TCR diagnostics can be used to identify shared clonotypes after allogeneic hematopoietic stem cell transplantation

被引:22
|
作者
O'Keefe, CL
Sobecks, RM
Wlodarski, M
Rodriguez, A
Bell, K
Kuczkowski, E
Bolwell, BJ
Maciejewski, JP
机构
[1] Cleveland Clin Fdn, Expt Hematol & Hematopoiesis Sect, Cleveland, OH 44195 USA
[2] Cleveland Clin Fdn, Bone Marrow Transplant Program, Cleveland, OH 44195 USA
关键词
D O I
10.1016/j.exphem.2004.07.013
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. In allogeneic hematopoietic stem cell (HSCT) transplantation, recovery of the T cell receptor (TCR) repertoire depends upon the composition of the graft and is modulated by peri-transplant immunosuppression, viral infections, and graft-vs-host disease (GVHD). We hypothesized that after allogeneic HSCT, molecular analysis of the TCR repertoire can be used to identify and quantitate immunodominant T cell clones that may play a role in GVHD or other clinical events. Methods. We utilized a rational strategy for the analysis of the expanded CTL clones. First, we studied the VB spectrum in a cohort of patients who had received either matched sibling or unrelated donor grafts. The CDR3 sequences of immunodominant clones were identified and clonotypic PCR and sequencing was applied to determine the level of clonotype sharing. Results. Significant expansions of VB families were observed following transplantations; 61% were oligo/monoclonal. Immunodeficiency was reflected by depletion of multiple VB families from both the CD8 and CD4 repertoires. The level of sharing varied between clonotypes, suggesting that some antigens have a more "public" spectrum while others are restricted to specific patients. Immunodominant CDR3 sequences common to allogeneic HSCT, healthy controls, and other conditions were identified. Conclusion. The clonotypes of expanded CTL clones may reflect responses to alloantigens (e.g., in correlation with clinical GVHD) or pathogens. In the future, molecular T cell diagnostics may become a powerful clinical tool in transplantation to monitor disease and to direct treatment. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc.
引用
收藏
页码:1010 / 1022
页数:13
相关论文
共 50 条
  • [1] Molecular T cell receptor diagnostics can be used to identify shared clonotypes in blood and tissue during GVHD.
    O'Keefe, CL
    Beck, R
    Rodriguez, A
    Howe, E
    Bell, K
    Bolwell, B
    Maciejewski, JP
    BLOOD, 2003, 102 (11) : 714A - 714A
  • [2] Strategies and clinical implications of chimerism diagnostics after allogeneic hematopoietic stem cell transplantation
    Thiede, C
    Bornhäuser, M
    Ehninger, G
    ACTA HAEMATOLOGICA, 2004, 112 (1-2) : 16 - 23
  • [3] Evaluation of allogeneic versus autologous TCR gene transfer after hematopoietic stem cell transplantation
    Koestner, W.
    Ghosh, A.
    Hapke, M.
    Vignali, D.
    Baum, C.
    Welte, K.
    Sauer, M.
    KLINISCHE PADIATRIE, 2008, 220 (03): : 204 - 204
  • [4] Erythrocytosis after allogeneic hematopoietic stem cell transplantation
    Hino, Yutaro
    Doki, Noriko
    Kurosawa, Shuhei
    Yamamoto, Keita
    Sakaguchi, Masahiro
    Harada, Kaito
    Ikegawa, Shuntaro
    Shingai, Naoki
    Hattori, Kenichiro
    Senoo, Yasushi
    Igarashi, Aiko
    Najima, Yuho
    Kobayashi, Takeshi
    Kakihana, Kazuhiko
    Sakamaki, Hisashi
    Ohashi, Kazuteru
    CLINICAL TRANSPLANTATION, 2017, 31 (04)
  • [5] Jaundice After Allogeneic Hematopoietic Stem Cell Transplantation
    Mendizabal, Manuel
    Chen, Terina
    Reddy, K. Rajender
    HEPATOLOGY, 2009, 50 (06) : 2044 - 2045
  • [6] Rhabdomyolysis After Allogeneic Hematopoietic Stem Cell Transplantation
    Q. Jiang
    B. H. Zhang
    Indian Journal of Hematology and Blood Transfusion, 2016, 32 : 504 - 506
  • [7] Malakoplakia After Allogeneic Hematopoietic Stem Cell Transplantation
    Robinson, Tracy
    Streu, Erin
    ONCOLOGY NURSING FORUM, 2015, 42 (05) : 558 - 561
  • [8] Rhabdomyolysis After Allogeneic Hematopoietic Stem Cell Transplantation
    Jiang, Q.
    Zhang, B. H.
    INDIAN JOURNAL OF HEMATOLOGY AND BLOOD TRANSFUSION, 2016, 32 (04) : 504 - 506
  • [9] Plasticity after allogeneic hematopoietic stem cell transplantation
    Rovo, Alicia
    Gratwohl, Alois
    BIOLOGICAL CHEMISTRY, 2008, 389 (07) : 825 - 836
  • [10] Polyomaviruses After Allogeneic Hematopoietic Stem Cell Transplantation
    Mendoza, Maria Alejandra
    Imlay, Hannah
    VIRUSES-BASEL, 2025, 17 (03):