The impact of acute antibody-mediated rejection (AAMR) on the long-term outcome on ABOincompatible (ABOIOur results indicate that AAMR has a heavy impact on the long-term outcome and preoperative DSHA appears to have a more significant association with poor graft outcomes than anti-blood group antibodies, even in ABOI kidney transplantation.

Several protocols allow the successful ABO incompatible living-related kidney transplantation (ABO-ILKTWe compared the patient and graft survival rates as well as the incidence rate of acute rejection in these two eras, when different regimens were used. There were significant differences in the 1-and 5-year graft survival rates between groups 1 and 2 (1-year: 78% in group 1 vs. 94% in group 2; 5-year: 73% in group 1 vs. 90% in group 2, p = 0.008). Also, a higher incidence rate of acute rejection was significantly observed in group 1 (50/105, 48%) than in group 2 (18/117, 15%) (p < 0.001). We conclude that the FK/MMF combination regimen provides excellent graft survival results in ABO-ILKT.

All contributing authors have declared that there is no relationship with any companies and no conflict of interest in this study.Numerous studies have shown that protocol biopsies have predictive power. We retrospectively examined the histologic findings and C4d staining in 89 protocol biopsies from 48 ABO-incompatible (ABO-I) transplant recipients, and compared the results with those of 250 controls from 133 ABO-compatible (ABO-C) transplant recipients given equivalent maintenance immunosuppression. Others have shown that subclinical rejection (borderline and grade I) in ABO-C grafts decreased gradually after transplantation. In our study, however, subclinical rejection in the ABO-I grafts was detected in 10%, 14% and 28% at 1, 3 and 6-12 months, respectively. At 6-12 months, mild tubular atrophy was more common in the ABO-C grafts whereas the incidence of transplant glomerulopathy did not differ between the two groups (ABO-C: 7%; ABO-I: 15%; p = 0.57). In the ABO-I transplants, risk factors for transplant glomerulopathy in univariate analysis were positive panel reactivity (relative risk, 45.0; p < 0.01) and a prior history of antibody-mediated rejection (relative risk, 17.9; p = 0.01). Furthermore, C4d deposition in the peritubular capillaries was detected in 94%, with diffuse staining in 66%. This deposition, however, was not linked to antibody-mediated rejection. We conclude that, in the ABO-I kidney transplantation setting, detection of C4d alone in protocol biopsies might not have any diagnostic or therapeutic relevance.

In this study, we examined the impact of preoperative anti-A/B antibody titers on the results of ABO-incompatible living kidney transplantation (LKT). In all, 167 recipients underwent ABO-incompatible LKT at our institution between 1989 and 2002. These patients were subdivided into those transplanted under cyclosporine with azathioprine or mizoribine (Group 1, n=78) and those transplanted under tacrolimus or mycophenolate mofetil (Group 2, n=89). Overall patient survival at 5 and 10 years was 93.8% and 88.0%, respectively. Overall graft survival at 5 and 10 years was 76.9% and 55.9%, respectively. Graft survival in the patients with anti-A/B IgG titers over 1:128 was significantly lower in group 1, whereas no significant correlation between the anti-A/B IgG titers and graft survival was found in group 2. In conclusion, no correlation between anti-A/B antibody titers and the results of ABO-incompatible LKT was seen after tacrolimus or mycophenolate mofetil application.

Alloreactive memory T cells are present in virtually all transplant recipients due to prior sensitization or heterologous immunity and mediate injury undermining graft outcome. In mouse models, endogenous memory CD8 T cells infiltrate MHC-mismatched cardiac allografts and produce IFN-γ in response to donor class I MHC within 24 hours post-transplant. The current studies analyzed the efficacy of anti-LFA-1 mAb to inhibit early CD8 T cell cardiac allograft infiltration and activation. Anti-LFA-1 mAb given to C57BL/6 6 (H-2b) recipients of A/J (H-2a) heart grafts on days −1 and 0 completely inhibited CD8 T cell allograft infiltration, markedly decreased neutrophil infiltration, and significantly reduced intra-graft expression levels of IFN-γ-induced genes. Donor-specific T cells producing IFN-γ were at low/undetectable numbers in spleens of anti-LFA-1 mAb treated recipients until day 21. These effects combined to promote substantial prolongation (from day 8 to 27) in allograft survival. Delaying anti-LFA-1 mAb treatment until days 3 and 4 post-transplant did not inhibit early memory CD8 T cell infiltration and proliferation within the allograft. These data indicate that peri-transplant anti-LFA-1 mAb inhibits early donor-reactive memory CD8 T cell allograft infiltration and inflammation suggesting an effective strategy to attenuate the negative effects of heterologous immunity in transplant recipients.