title: Pretransplant donor and recipient CTLA-4 mRNA and protein levels as a prognostic marker for aGvHD in allogeneic hematopoietic stem cell transplantation.
abstract: BACKGROUND
  Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory T cells' receptor essential for maintaining T cell homeostasis and immunotolerance. The role of the co-stimulatory pathway in development of aGvHD has been studied mostly in animal models. To the best of our knowledge, there are no published data on the role of CTLA-4 in pathogenesis of aGvHD after hematopoietic stem cell transplantation (HSCT) in humans. Therefore the aim of our study was to determine the association of CTLA-4 mRNA and proteins level in HSCT donor-recipient pairs, prior to and after HSCT, with aGvHD risk.
  
  
  METHODS
  Total CTLA-4 mRNA level in 51 donor-recipient pairs prior to and 56 days after HSCT was determined using real time PCR techniques, while membrane (m) and cytoplasmic (c) CTLA-4 expression in CD3+ cells were measured by flow cytometry in 40 donor-recipient pairs at the same time points.
  
  
  RESULTS
  We found an association between the risk of aGvHD and high pre-transplant CTLA-4 mRNA expression level both in recipients and in donors, stronger in recipients (OR=2.02, CI95% 1.39-3.01), and less pronounced in donors (OR=1.57, CI95% 1.18-2.0). Moreover, we showed that proportion of CD3+ cells positive for mCTLA-4 in recipients prior to HSCT positively correlated with increased risk of aGvHD (OR=1.175, CI95% 1.024-1.311, p=0.018).
  
  
  CONCLUSIONS
  Our results indicate that both donor and recipient CTLA-4 mRNA as well as recipient membrane protein expression levels measured before transplantation may be considered as prognostic factors for aGvHD development.
authors.affiliation: Department of Experimental Therapy, L. Hirszfeld Institute of Immunology & Experimental Therapy, R Weigl St 12, Wroclaw 53-114, Poland; Department and Clinic of Urology, Wroclaw Medical University, Borowska St 213, 50-556 Wroclaw, Poland. Electronic address: lkarabon@iitd.pan.wroc.pl.
authors.forename: Lidia
authors.initials: L
authors.lastname: Karabon
authors.affiliation: School of Medicine in Katowice, Medical University of Silesia, Dabrowskiego St 25, 40-032 Katowice, Poland.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Markiewicz
authors.affiliation: Department of Experimental Therapy, L. Hirszfeld Institute of Immunology & Experimental Therapy, R Weigl St 12, Wroclaw 53-114, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Kosmaczewska
authors.affiliation: Department of Experimental Therapy, L. Hirszfeld Institute of Immunology & Experimental Therapy, R Weigl St 12, Wroclaw 53-114, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Partyka
authors.affiliation: Department of Experimental Therapy, L. Hirszfeld Institute of Immunology & Experimental Therapy, R Weigl St 12, Wroclaw 53-114, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Pawlak-Adamska
authors.affiliation: Department of Experimental Therapy, L. Hirszfeld Institute of Immunology & Experimental Therapy, R Weigl St 12, Wroclaw 53-114, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Tomkiewicz
authors.affiliation: Department of Experimental Therapy, L. Hirszfeld Institute of Immunology & Experimental Therapy, R Weigl St 12, Wroclaw 53-114, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Ciszak
authors.affiliation: School of Medicine in Katowice, Medical University of Silesia, Dabrowskiego St 25, 40-032 Katowice, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Jagoda
authors.affiliation: School of Medicine in Katowice, Medical University of Silesia, Dabrowskiego St 25, 40-032 Katowice, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Dzierzak-Mietla
authors.affiliation: School of Medicine in Katowice, Medical University of Silesia, Dabrowskiego St 25, 40-032 Katowice, Poland.
authors.forename: Slawomira
authors.initials: S
authors.lastname: Kyrcz-Krzemien
authors.affiliation: Department of Experimental Therapy, L. Hirszfeld Institute of Immunology & Experimental Therapy, R Weigl St 12, Wroclaw 53-114, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Frydecka
mesh_terms: D000208:Acute Disease; D000328:Adult; D060908:CTLA-4 Antigen / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D012372:ROC Curve; D014019:Tissue Donors; D066027:Transplant Recipients; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D060908:CTLA-4 Antigen; D012333:RNA, Messenger
keywords: Acute graft vs host disease; CTLA-4; Hematopoietic stem cell transplantation; Protein expression level; mRNA expression level