Antibody monitoring in pancreas transplantation. Subclinical rejection in protocol biopsies in patients with DSA antibodies

UVA P; LEON L; MINUE E; CABRERA I; CHULUYAN E; TONIOLO F; CASADEI D

Melbourne

Congreso; 15th World Congress of the International Pancreas and Islet Transplant Association; 2015

The Transplantation Society - TTS

In kidney transplantation de novo donor-specific (DSA) HLA antibodies have been found to correlate to poor graft survival and Consensus Guidelines recommend a protocol biopsy. In pancreas transplantation DSA antibodies had also been associated with poor graft outcomes and many centers have antibody screening protocols. We here report results of our screening protocol which includes several kidney-pancreas biopsies. This study excludes antibody testing in the setting of dysfunction.ResultsDuring the study period 93 pancreas transplant recipients with stable graft function were screened for HLA antibodies by Luminex. There were 2 pancreas transplants alone (PTA), 3 pancreas after kidney (PAK), and 88 simultaneous pancreas-kidney transplants (SPK). There were 2 pancreas retransplants, an SPK after PTA and a PAK after SPK. There were 84 type 1 and 9 type 2 diabetic patients. 71 were enteric drained and 22 bladder drained. 22 patients had a history of rejection before their first antibody screening. Negative Antibodies72 patients had negative anti-HLA antibodies (16 had a previous rejection episode). Of these, 8 patients had kidney and pancreas biopsies performed for different reasons (incisional hernia repair, protocol biopsies for immunosuppression modifications, detection of BKV viremia, etc) and none of them had signs of rejection on pathology. 24 of these 72 patients had a second antibody screening performed which resulted negative in 18 and positive in 6 patients (all non-DSA). 4 of these 72 patients presented kidney dysfunction and were biopsied. At this time 1 patient showed kidney acute cellular rejection (ACR) grade Banff 1A and normal pancreas with negative antibodies, another patient showed a kidney acute antibody mediated rejection (AMR) and normal pancreas with negative antibodies and two patients showed kidney and pancreas ACR with positive non-DSA antibodies. In one of these patients antibodies became negative 5 months later after treatment with steroids and Thymoglobulin .Positive Antibodies21 patients had positive anti-HLA antibodies at screening. 6 of them had a previous history of rejection. 13 patients had non-DSA antibodies. Of these, 7 patients with moderate to high MFI were biopsied with no proof of rejection on pathology. None of these experienced graft dysfunction during follow-up. 6 of these 13 patients had a second screening with 2 patients with negative antibodies. The other 8 patients with positive antibodies had DSA antibodies. 3 patients are awaiting biopsy with no signs of dysfunction. 1 patient with a previous history of AMR with moderate DSA antibodies reduced to low DSA antibodies after treatment with normal follow up biopsy. 3 patients were biopsied showing subclinical ACR with C4d negative. Treatment with PP, IVIG and Rituximab resulted in preserved graft function at five months follow up with 2 patients with negative antibodies and 1 decreasing DSA antibodies. The last patient presented with pancreas dysfunction before the scheduled biopsy. At that time biopsy showed kidney and pancreas ACR and after treatment with PP- IVIG and Rituximab the patient lost pancreas graft function. Discussion: We report an 8.6% of positive DSA antibodies. Among them, 1 had a previous AMR, 1 presented with dysfunction with an ACR and lost the pancreas graft and 3 had subclinical rejection on protocol biopsy with good response to treatment.