Loss of endothelial thrombomodulin predicts response to steroid therapy and survival in acute intestinal graft-versus-host disease.
Steroid-refractory graft-versus-host disease causes significant morbidity and mortality after allogeneic stem cell transplantation. The pathomechanism of steroid resistance is currently not understood, but it has been suggested that endothelial cell dysfunction plays a role. Endothelial thrombomodulin was quantified along with histological markers of epithelial damage and cytotoxic T cells in colon biopsies from 51 allografted patients, and retrospectively correlated with response to steroids and survival. Loss of endothelial thrombomodulin was the strongest predictor of response to steroids (P=0.02) and nonrelapse mortality (P=0.01) in multivariate analyses adjusting for T-cell infiltrates, histological grading, vessel density, disease status, donor type, and conditioning therapy. Our data provide evidence that at disease onset, loss of endothelial thrombomodulin expression rather than excessive T-cell infiltration associates with steroid-refractory graft-versus-host disease and mortality. Prospective histological investigations are now warranted to improve diagnosis and prognostication of this core complication of stem cell transplantation.
Institute of Pathology, University Hospital Heidelberg, Freiburg, Germany.
Mindaugas
M
Andrulis
Sascha
S
Dietrich
Thomas
T
Longerich
Ronald
R
Koschny
Maria
M
Burian
Annette
A
Schmitt-Gräf
Peter
P
Schirmacher
Anthony D
AD
Ho
Peter
P
Dreger
Thomas
T
Luft
D018572:Disease-Free Survival; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007410:Intestinal Diseases / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013256:Steroids / Q000008:administration & dosage*; D015996:Survival Rate; D018180:Thrombomodulin / Q000096:biosynthesis*; D014184:Transplantation, Homologous
D013256:Steroids; C546931:THBD protein, human; D018180:Thrombomodulin