Impact of HLA matching on the outcome of simultaneous pancreas-kidney transplantation

Background. Simultaneous pancreas-kidney (SPK) transplantation has become the therapy of choice for type 1 diabetic patients with end-stage renal disease. The current analysis examined the impact of human leukocyte antigen (HLA) matching on graft outcome following SPK transplantation. The study population was obtained from patients enrolled in the Euro-SPK 001 study. Methods. The effect of HLA matching on graft function and survival was assessed in 180 SPK recipients in whom complete donor-recipient HLA data were available. A group of 45 patients with 0-3 HLA mismatches (MM) was compared with a group of 135 patients with 4-6 MM. Results. There were no differences in 3-year kidney, pancreas or patient survival between the 0-3 and 4-6 MM groups. Biological parameters of kidney and pancreas graft function were similar in both groups. Significantly more patients with 0-3 MM (66%) were rejection-free at 3 years than was the case among those with 4-6 MM (41%; P = 0.003). The relative risk of acute rejection was 2.6 times higher among patients with 4-6 MM than among those with 0-3 MM. Conclusions. There was no evidence that HLA matching was associated with improved kidney or pancreas survival. However, a higher rate of acute rejection was observed with poor HLA match, which may impact long-term surviva

Endocrine secretory reserve and proinsulin processing in recipients of islet of langerhans versus whole pancreas transplants

β-Cells have demonstrated altered proinsulin processing after islet transplantation. We compare β-cell metabolic responses and proinsulin processing in pancreas and islet transplant recipients with respect to healthy control subjects

Islet autotransplantation after extended pancreatectomy for focal benign disease of the pancreas

Extended pancreatectomy is associated with the risk of surgical diabetes. Islet autotransplantation is successful in the prevention of diabetes after pancreas resection for chronic pancreatitis (CP), with insulin independence rates of 50% at 1 year. The aim of the present study is to demonstrate the safety and efficiency of islet autotransplantation after extended left pancreatectomy for benign disease

Low risk of anti-human leukocyte antigen antibody sensitization after combined kidney and islet transplantation

Anti-human leukocyte antigen (HLA) antibody could lead to humoral rejection and a decrease in graft survival after kidney transplantation. A recent report has suggested that islet transplantation alone is associated with a high rate of sensitization. The withdrawal of the immunosuppressive therapy because of the progressive nonfunction of the islets could explain the high rate of sensitization. Because the specific risk of immunization of multiple islet infusions remains unknown, we studied the immunization rate in our cohort of multiple islet infusions transplant recipients. De novo anti-HLA antibodies were analyzed in 37 patients after islets alone (n=8), islet-after-kidney (n=13), and simultaneous islet-kidney (n=16) transplantation by solid phase assays over time. The rate of immunization was 10.8% that is comparable with the risk of immunization after kidney transplantation alone. Multiple islet infusions do not represent a specific risk for the development of anti-HLA antibodies after combined kidney-islets transplantation

Pancreas retransplantation: a second chance for diabetic patients?

If pancreas transplantation is a validated alternative for type 1 diabetic patients with end-stage renal disease, the management of patients who have lost their primary graft is poorly defined. This study aims at evaluating pancreas retransplantation outcome

Posttransplant cellular immune reactivity against donor antigen correlates with clinical islet transplantation outcome: towards a better posttransplant monitoring

The aim of the present study was to assess the efficiency of cell-based immune assays in the detection of alloreactivity after islet transplantation and to correlate these results with clinical outcome. Mixed lymphocyte cultures were performed with peripheral blood mononuclear cells from recipients (n = 14), donors, or third party. The immune reactivity was assessed by the release of IFN-γ (ELISpot), cell proliferation (FACS analysis for Ki67), and cytokine quantification (Bioplex). Islet function correlated with the number of IFN-γ-secreting cells following incubation with donor cells (p = 0.007, r = -0.50), but not with third party cells (p = 0.61). Similarly, a high number of donor-specific proliferating cells was associated with a low islet function (p = 0.006, r = -0.51). Proliferating cells were mainly CD3(+)CD4(+) lymphocytes and CD3(-)CD56(+) natural killer cells (with low levels of CD3(+)CD8(+) lymphocytes). Patients with low islet function had increased levels of CD4(+)Ki67(+)cells (p ≤ 0.0001), while no difference was observed in CD8(+)Ki67(+) and CD56(+)Ki67(+) cells. IFN-γ, IL-5, and IL-17 levels were increased in patients with low islet function, but IL-10 levels tended to be lower. IFN-γ-ELISpot, proliferation, and cytokines were similarly accurate in predicting clinical outcome (AUC = 0.77 ± 0.088, 0.85 ± 0.084, and 0.88 ± 0.074, respectively). Cellular immune reactivity against donor cells correlates with posttransplant islet function. The tested assays have the potential to be of substantial help in the management of islet graft recipients and deserve prospective validation

Alloimmune Monitoring after Islet Transplantation: A Prospective Multicenter Assessment of 25 Recipients

International audienceIslet transplantation is an effective treatment for selected patients with type 1 diabetes. However, an accurate test still lacks for the early detection of graft rejection. Blood samples were prospectively collected in four university centers (Geneva, Grenoble, Montpellier, and Strasbourg). Peripheral blood mononuclear cells were stimulated with donor splenocytes in the presence of interleukin-2. After 24 h of incubation, interferon- (IFN-) ELISpot analysis was performed. After a total of 5 days of incubation, cell proliferation was assessed by fluorescence-activated cell sorting (FACS) analysis for Ki-67. Immunological events were correlated with adverse metabolic events determined by loss of 1 point of -score and/or an increased insulin intake 10%. Twenty-five patients were analyzed; 14 were recipients of islets alone, and 11 combined with kidney. Overall, 76% (19/25) reached insulin independence at one point during a mean follow-up of 30.7 months. IFN- ELISpot showed no detectable correlation with adverse metabolic events [area under the curve (AUC)=0.57]. Similarly, cell proliferation analysis showed no detectable correlation with adverse metabolic events (CD3+/CD4+ AUC=0.54; CD3+/CD8+ AUC=0.55; CD3/CD56+ AUC=0.50). CD3/CD56+ cell proliferation was significantly higher in patients with combined kidney transplantation versus islet alone (6 months, p=0.010; 12 months, p=0.016; and 24 months, p=0.018). Donor antigen-stimulated IFN- production and cell proliferation do not predict adverse metabolic events after islet transplantation. This suggests that the volume of transplanted islets is too small to produce a detectable systemic immune response and/or that alloimmune rejection is not the sole reason for the loss of islet graft function

Comparative impact on islet isolation and transplant outcome of the preservation solutions Institut Georges Lopez-1, University of Wisconsin, and Celsior

Institut Georges Lopez-1 (IGL-1) is a preservation solution similar to University of Wisconsin (UW) with reversed Na/K contents. In this study, we assessed the impact of IGL-1, UW, and Celsior (CS) solutions on islet isolation and transplant outcome