Isolated Pre-existing HLA-DP Donor-Specific Antibodies are Associated With Poorer Outcomes in Renal Transplantation.

Introduction: The importance of donor-specific antibodies (DSAs) in renal transplantation has long been recognized, but the significance of human leukocyte antigen (HLA)-DP antibodies remains less clear. We performed a retrospective single center study of renal transplants with pre-existing isolated HLA-DP-DSAs to assess clinical outcomes. Methods: Twenty-three patients with isolated HLA-DP-DSAs were compared with 3 control groups as follows: standard immunological risk (calculated reaction frequency [cRF] < 85%, no current or historical DSA, no repeat mismatched antigens with previous transplants, n = 46), highly sensitized (cRF > 85%, n = 27), and patients with HLA-DP antibodies that were not donor-specific (n = 18). Univariate and multivariate analyses were performed comparing antibody-mediated rejection (ABMR)-free and graft survival. Factors in the final multivariable models included patient group, % cRF, B-cell flow crossmatch (BFXM) positivity and regrafts. Results: Over a median follow-up of 1197 days, 65% of HLA-DP-DSA patients had ABMR on indication biopsies, and 30% of HLA-DP-DSA patients lost their graft. Pre-existing HLA-DP DSAs remained the single factor associated with ABMR after multivariable analysis (hazard ratio [HR] = 9.578, P = 0.012). Patients with HLA-DP DSAs had increased microvascular scores (P = 0.0346) and worse transplant glomerulopathy (P = 0.015) on biopsy compared with the standard immunological risk group. Furthermore, flow crossmatch (FXM) positivity did not help inform on the risk of graft failure or ABMR in patients with preformed DP-DSA. Conclusion: Transplants with pre-existing HLA-DP-DSAs should be considered high risk. Routine laboratory tests are unable to further risk stratify these patients. Recipients should be considered for intensified immunosuppression and closely monitored.

C3d-positive donor-specific antibodies have a role in pretransplant risk stratification of cross-match-positive HLA-incompatible renal transplantation: United Kingdom multicentre study.

Anti-HLA-antibody characteristics aid to risk-stratify patients and improve long-term renal graft outcomes. Complement activation by donor-specific antibody (DSA) is an important characteristic that may determine renal allograft outcome. There is heterogeneity in graft outcomes within the moderate to high immunological risk cases (cross-match-positive). We explored the role of C3d-positive DSAs in sub-stratification of cross-match-positive cases and relate to the graft outcomes. We investigated 139 cross-match-positive living-donor renal transplant recipients from four transplant centres in the United Kingdom. C3d assay was performed on serum samples obtained at pretreatment (predesensitization) and Day 14 post-transplant. C3d-positive DSAs were found in 52 (37%) patients at pretreatment and in 37 (27%) patients at Day 14 post-transplant. Median follow-up of patients was 48 months (IQR 20.47-77.57). In the multivariable analysis, pretreatment C3d-positive DSA was independently associated with reduced overall graft survival, the hazard ratio of 3.29 (95% CI 1.37-7.86). The relative risk of death-censored five-year graft failure was 2.83 (95% CI 1.56-5.13). Patients with both pretreatment and Day 14 C3d-positive DSAs had the worst five-year graft survival at 45.5% compared with 87.2% in both pretreatment and Day 14 C3d-negative DSA patients with the relative risk of death-censored five-year graft failure was 4.26 (95% CI 1.79, 10.09). In this multicentre study, we have demonstrated for the first time the utility of C3d analysis as a distinctive biomarker to sub-stratify the risk of poor graft outcome in cross-match-positive living-donor renal transplantation.

Prolonged survival after the surgical management of a solitary malignant melanoma lesion within the pancreas: A case report of curative resection.

Solitary involvement of the pancreas in patients with malignant melanoma is rare and the role of surgery in these patients is not defined. We present a patient with prolonged survival following aggressive surgical management for a solitary metastatic lesion within the pancreas. A 69-year-old male presented with a 10-day history of painless jaundice. His past medical history included a wide local excision for a superficial spreading melanoma, and subsequent loco-regional recurrence requiring lymph node dissection. Imaging on presentation showed a solitary mass in the head of the pancreas, with no signs of metastases. The patient underwent a pancreato-duodenectomy. Histology reported a metastatic malignant melanoma with clear excision margins. There was no nodal involvement and he remained disease-free eight years later. The survival of patients seems to be affected by the ability to perform a curative resection, and by a long disease-free interval between the treatment of the initial lesion and disease recurrence. Curative surgical resection should be offered to selected patients with a solitary pancreatic malignant melanoma metastasis. Such aggressive management may lead to prolonged, and disease-free survival.