Increased immune transcript levels are correlated with acute graft-versus-host disease and cytomegalovirus response after allogeneic stem cell transplantation.
BACKGROUND
Donor T cells are primarily responsible for graft-versus-host disease (GVHD). Three effector pathways have been described for T-cell cytotoxicity: granzyme B/perforin, Fas/Fas ligand (FasL), and secreted molecules such as tumor necrosis factor (TNF)-alpha. Therefore, this study evaluates the gene expression pattern in the peripheral blood of patients after allogeneic stem cell transplantation and correlates the results to acute GVHD.


METHODS
Real-time quantitative reverse transcriptase-polymerase chain reaction was used to quantify the gene expression of granzyme B, perforin, FasL, and TNF-alpha in peripheral blood from 53 patients.


RESULTS
Samples were available from 27 of the 38 patients with acute GVHD diagnoses. Increased gene expression (>50%) during acute GVHD was detected in 23 of 27, 26 of 27, and 24 of 27 patients for granzyme B, perforin, and FasL, respectively. TNF-alpha showed a diffuse correlation. The median increases were as follows: granzyme B, 7.2x (1.6-183.2); perforin, 5.8x (1.6-254.9); and FasL, 8.5x (1.5-895.6). We also showed that all of the 10 patients with increasing levels of granzyme B, perforin, and FasL during steroid treatment demonstrated persistent or deteriorating GVHD. Patients with increasing transcription levels during cytomegalovirus (CMV) reactivation responded significantly better to therapy than those with declining levels. A total of 13 of 17 patients with increasing levels versus 0 of 11 patients with decreasing levels responded well to CMV treatment (P<0.01).


CONCLUSIONS
Although not specific for acute GVHD, quantitative assessment of immune transcripts may be of value in diagnosing and monitoring acute GVHD. It may also serve as a guide for the clinician in detecting patients who respond poorly to CMV therapy.
Jaksch
Marie
M
Division of Clinical Immunology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden. Marie.Jaksch@labmed.ki.se
Remberger
Mats
M
Mattsson
Jonas
J
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003586:Cytomegalovirus Infections / Q000150:complications*; D053222:Fas Ligand Protein; D005260:Female; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000150:complications / Q000276:immunology*; D053804:Granzymes; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D014158:Transcription, Genetic / 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; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases