Combining altered levels of effector transcripts in circulating T cells with a marker of endothelial injury is specific for active graft-versus-host disease.
Cytotoxic T lymphocytes (CTLs) are important effector cells of graft-versus-host disease (GVHD) and vascular endothelial cells are target cells of allospecific CTL. A combined assessment of T-cell activation and endothelial injury should result in a specific and sensitive test for GVHD. We examined circulating T lymphocytes for effector molecules involved in CTL-mediated endothelial injury. We analyzed CD4 and CD8 T lymphocytes of 24 long-term survivors of allogeneic stem cell transplantation with or without GVHD, and nine healthy, age-matched controls for signs of CTL activation and endothelial injury. IFN-gamma transcript levels in CD8 T cells were significantly elevated in SCT recipients with GVHD compared to patients without GVHD (767 CD3epsilon units/T cell (376-2050) vs 211 CD3epsilon units/T cell (159-274), P=0.01). Fas ligand transcript levels in CD4 T cells were significantly elevated in SCT recipients without GVHD compared to patients with GVHD (20 CD3epsilon units/T cell (0-78) vs 0 CD3epsilon units/T cell (0-0), P=0.01). Von Willebrand factor plasma levels were high in patients with GVHD, but normal in patients without GVHD (209 (186-254) vs 120 (100-141), P=0.0005). This assessment of T-cell activation and endothelial injury results in a sensitive and specific test to identify patients with active chronic GVHD.
Biedermann
B C
BC
Department of Medicine, University Hospital Bruderholz, Bruderholz, Switzerland. barbara.biedermann@ksbh.ch
Tsakiris
D A
DA
Gregor
M
M
Pober
J S
JS
Gratwohl
A
A
D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000473:pathology*; D053222:Fas Ligand Protein; D006086:Graft vs Host Disease / Q000175:diagnosis*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D007371:Interferon-gamma / Q000235:genetics; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics; D025202:Molecular Diagnostic Techniques; D012333:RNA, Messenger / Q000032:analysis*; D012680:Sensitivity and Specificity; D017741:Survivors; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D014184:Transplantation, Homologous; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014841:von Willebrand Factor; D007371:Interferon-gamma