Increased levels of immune transcript in patients with acute GVHD after allogeneic stem cell transplantation.
After allogeneic stem cell transplantation (SCT), donor T-cells are primarily responsible for the antihost activity, resulting in graft-versus-host disease (GVHD). Three effector pathways have been described for T-cell cytotoxicity: perforin/granzyme B; Fas/Fas ligand (FasL) and secreted molecules such as TNF-alpha. The goal of this pilot study was to utilize competitive reverse transcription (RT)-PCR to evaluate the pattern of granzyme B, perforin, FasL and TNF-alpha gene expression in peripheral blood in patients after SCT. Protein levels of granzyme B, soluble FasL (sFasL) and TNF-alpha in plasma were also analyzed. Eight patients who underwent allogeneic SCT were included; five were diagnosed with acute GVHD. In the patients diagnosed with acute GVHD, we found increased levels of granzyme B, perforin and FasL mRNA, although this did not correlate with the clinical severity. However, patients with increasing levels of gene expression during acute GVHD treatment may have an increased risk of developing severe acute GVHD, as two out of three patients with increasing immune transcript levels during GVHD therapy developed life-threatening acute GVHD. In conclusion, the quantitative RT-PCR of granzyme B, perforin and FasL may serve as a guide to the clinician in diagnosing acute GVHD and monitoring treatment.
Jaksch
M
M
Division of Clinical Immunology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden.
Uzunel
M
M
Martinez Cangana
G
G
Remberger
M
M
Mattsson
J
J
D000208:Acute Disease; D000328:Adult; D053222:Fas Ligand Protein; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology; D053804:Granzymes; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013997:Time Factors; D014158:Transcription, Genetic / Q000276:immunology*; D014184:Transplantation, Homologous / Q000009:adverse effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases