Pretransplant donor and recipient CTLA-4 mRNA and protein levels as a prognostic marker for aGvHD in allogeneic hematopoietic stem cell transplantation.
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).


CONCLUSION
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.
['Karabon|Lidia|L|', 'Markiewicz|Miroslaw|M|', 'Kosmaczewska|Agata|A|', 'Partyka|Anna|A|', 'Pawlak-Adamska|Edyta|E|', 'Tomkiewicz|Anna|A|', 'Ciszak|Lidia|L|', 'Jagoda|Krystyna|K|', 'Dzierzak-Mietla|Monika|M|', 'Kyrcz-Krzemien|Slawomira|S|', 'Frydecka|Irena|I|']
D000208:Acute Disease D000328:Adult D060908:CTLA-4 Antigen D005260:Female D015870:Gene Expression D006086:Graft vs Host Disease D018380:Hematopoietic Stem Cell Transplantation D006801:Humans D008297:Male D008875:Middle Aged D011379:Prognosis D012333:RNA, Messenger D012372:ROC Curve D014019:Tissue Donors D066027:Transplant Recipients D014184:Transplantation, Homologous D055815:Young Adult
CTLA-4 Hematopoietic stem cell transplantation mRNA expression level Protein expression level Acute graft vs host disease