Abstract
Pre-transplant screening focuses on the detection of anti-HLA alloantibodies. Previous studies have shown that IFN-γ and IL-21 producing T cells are associated with the development of acute rejection (AR). The aim of this study, was to assess whether pre-transplant donor-reactive T cells and/or B cells are associated with increased rejection risk. Samples from 114 kidney transplant recipients (transplanted between 2010 and 2013) were obtained pre-transplantation. The number of donor-reactive IFN-γ and IL-21 producing cells was analyzed by ELISPOT assay. The presence of donor specific antibodies (DSA) was also determined before transplantation. Numbers of donor-reactive IFN-γ producing cells were similar in patients with or without AR whereas those of IL-21 producing cells were higher in patients with AR (p = 0.03). Significantly more patients with AR [6/30(20%)] had detectable DSA compared to patients without AR [5/84(5.9%), p = 0.03]. Multivariate logistic regression showed that donor age (OR 1.06), pre-transplant DSA (OR 5.61) and positive IL-21 ELISPOT assay (OR 2.77) were independent predictors of an increased risk for the development of AR. Aside from an advanced donor-age and pre-transplant DSA, also pre-transplant donor-reactive IL-21 producing cells are associated with the development of AR after transplantation.
Highlights
The incidence of acute rejection (AR) has been reduced since the introduction of tacrolimus with mycophenolate mofetil combination therapy[1]
Univariate analysis showed that donor age, historical PRA, presence of anti-human leukocyte antigen (HLA) antibodies and donor specific antibodies (DSA) were significantly higher in patients who experienced rejection within the first 6 months after transplantation compared to non-rejectors
The aim of this study was to investigate whether donor-reactive IFN-γ producing cells, donor-reactive IL-21 producing cells and B cell alloreactivity were associated with an increased rejection risk after kidney transplantation
Summary
The incidence of acute rejection (AR) has been reduced since the introduction of tacrolimus with mycophenolate mofetil combination therapy[1]. B cells are involved in several mechanisms that can contribute to the development of allograft rejection These include antigen presentation, cytokine production and differentiation into alloantibodyproducing plasma cells[11,12]. Current pre-transplant screening mainly focuses on the detection of anti-HLA alloantibodies present in the serum of transplant c andidates[17] This strategy, does not account for the presence of donor-reactive memory T cells which may contribute to allograft rejection. A long-standing area of transplant research has focused on the development of in vitro methods that allow for the accurate detection of donor-specific T cell alloimmunity[18,19] One such method was developed by Heeger et al, involving the use of an enzyme-linked immunosorbent spot (ELISPOT) assay in which donor-reactive memory IFN-γ producing T cells could be measured[20]. The aim of this study, was to assess whether donor-reactive IFN-γ and IL-21 producing T cells and B cell donor reactivity assessed pre-transplantation in kidney transplant recipients are associated with an increased rejection risk after transplantation
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