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

Abstract

BackgroundCytotoxic 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. MethodsTotal 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. ResultsWe 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). ConclusionOur 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.