Gene Expression in Human Acute Cutaneous and Hepatic Graft-Versus-Host Disease after Allogeneic Bone Marrow Transplantation

Abstract

Hematopoietic stem cell (HSC) allograft can be performed with cells of peripheral or medullar origin. Currently, it is the best therapy for certain malignant diseases. The curative power of allografts is based on conditioning and on the graft versus leukemia (GVL) effect. This effect is always associated with a toxic reaction called graft-versus-host disease (GVHD). Numerous studies have been carried out on mouse models, but the pathophysiology of GVHD remains unknown. To evaluate the variation in gene expression during GVHD, a prospective study was performed on two patients with GVHD, using the donors as controls. Blood lymphocytes were isolated by Ficoll gradient. The gene expression levels in total RNA were determined using the Taqman method. The gene expressions of cytokines (TNFα, INFγ, IL4, IL10), major histocompatibility complex class II (MHC II) and class III (BAT2), an adhesion molecule (VCAM) and granzyme M were studied. INFγ, TNFα, BAT2 and IL4 were up-regulated whereas IL10 and VCAM1 were down-regulated.