title: Gene expression profile of cytokines in patients with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with reduced conditioning.
abstract: There are no reliable markers useful to predict the onset or the evolution of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT), although several candidate biomarkers have been identified from limited hypothesis-driven studies. In this study we evaluated 14 patients who received a reduced intensity conditioning HSCT. Seven patients had cGVHD, whereas 7 never developed cGVHD during the period of observation. The expression of 114 cytokines in immunoselected cell populations was explored by microarray analysis and 11 cytokines were selected for further evaluation by real-time PCR. Differential gene expression measurements showed a significant up-regulation for INFγ (interferon, gamma) in CD8+ and for TNFSF3 (tumor necrosis factor superfamily, member 3) and for TNFSF10 (tumor necrosis factor superfamily, member 10) in CD14+ cell population when comparing cGVHD with control samples. The expression levels were significantly decreased for TNFSF10 in CD8+ cell population and for TNFSF12 (tumor necrosis factor superfamily, member 12) and for PDGFβ (platelet-derived growth factor, beta) in CD4+. Our data seem to suggest that different immune populations can play a role in cGVHD pathogenesis and the early detection of gene expression profile in these patients could be useful in the monitoring of GVHD. We hypothesized that PDGFβ down-regulation could represent a negative feedback to compensate for enhanced expression of its receptor recently reported.
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche-Sezione di Ematologia, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Poloni
authors.forename: Davide
authors.initials: D
authors.lastname: Sartini
authors.forename: Monica
authors.initials: M
authors.lastname: Emanuelli
authors.forename: Silvia
authors.initials: S
authors.lastname: Trappolini
authors.forename: Stefania
authors.initials: S
authors.lastname: Mancini
authors.forename: Valentina
authors.initials: V
authors.lastname: Pozzi
authors.forename: Benedetta
authors.initials: B
authors.lastname: Costantini
authors.forename: Federica
authors.initials: F
authors.lastname: Serrani
authors.forename: Eleonora
authors.initials: E
authors.lastname: Berardinelli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Renzi
authors.forename: Attilio
authors.initials: A
authors.lastname: Olivieri
authors.forename: Pietro
authors.initials: P
authors.lastname: Leoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002908:Chronic Disease; D000074049:Cytokine TWEAK; D016207:Cytokines / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D053308:Lymphotoxin-beta / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D048069:Tumor Necrosis Factors / Q000235:genetics; D055815:Young Adult
chemical_list: D000074049:Cytokine TWEAK; D016207:Cytokines; C505886:LTB protein, human; D053308:Lymphotoxin-beta; D020574:Proto-Oncogene Proteins c-sis; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors; D007371:Interferon-gamma