High-content flow cytometry and temporal data analysis for defining a cellular signature graft-versus-host disease

被引:45
作者
Brinkman, Ryan Remy
Gasparetto, Maura
Lee, Shang-Jung Jessica
Ribickas, Albert J.
Perkins, Janelle
Janssen, William
Smiley, Renee
Smith, Clay
机构
[1] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada
[2] H Lee Moffitt Canc Ctr & Res Inst, Vancouver, BC, Canada
关键词
graft-versus-host disease; high content flow cytometry; bioinformatics;
D O I
10.1016/j.bbmt.2007.02.002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Acute graft-versus-host disease (GVHD) is diagnosed by clinical and histologic criteria that are often nonspecific and typically apparent only after the disease is well established. Because GvHD is mediated by donor T cells and other immune effector cells, we sought to determine whether changes within a wide array of peripheral blood lymphocyte populations could predict the development of GvHD. Peripheral blood samples from 31 patients undergoing allogeneic blood and marrow transplant were analyzed for the proportion of 121 different subpopulations defined by 4-color combinations of lymphocyte phenotypic and activation markers at progressive time points posttransplant. Samples were processed using a newly developed high content flow cytometry technique and subjected to a spline- and functional linear discriminant analysis (FLDA)-based temporal analysis technique. This strategy identified a consistent posttransplant increase in the proportion and extent of fluctuation of CD3(+)CD4(+)CD8 beta(+) cells in patients who developed GVHD compared to those that did not. Although larger prospective clinical studies will be necessary to validate these results, this study demonstrates that high-content flow cytometry coupled with temporal analysis is a powerful approach for developing new diagnostic tools, and may be useful for developing a sensitive and specific predictive test for GVHD. (C) 2007 American Socicty for Blood and Marrow Transplantation.
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页码:691 / 700
页数:10
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