Introduction: Few studies have evaluated the role of donor-specific antibodies(DSA) in pancreas transplantation(PT). The aim of this study was to analyze the incidence of DSA pre and post-PT and outcomes in a protocol of routine DSA monitoring.

Results: From March/2018 to December/2021, 234 technical successful PT, being 135 SPK and 99 solitary PT(S-PT), of which 86 PAK and 13 PTA, were followed for detection of post-transplant(PO) DSA. All PT received induction therapy with Thymoglobulin, tacrolimus, mycophenolate sodic and steroids. Screening of HLA-antibodies was performed by Luminex at 3, 6 and 12 months PO or when a rejection episode occurred and twice a year thereafter for all S-PT. Any DSA with value >500 MFI was registered. All kidney or pancreas rejection was biopsy-proven and stained for C4d. Pretransplant DSAs were found in 4 SPK and 7 S-PT recipients, all <1500 of MFI. The prevalence of de novo DSA was significantly higher among S-PT, 19(19%), compared to SPK recipients, 12(8.9%), p=0.03, OR=2.43. The average time of DSA appearance was 6.4 months(3-28) and most of them, 25(80.6%), were triggered after a rejection episode. Overall, more rejection episodes were observed in patients with DSA+ than in DSA- (80.6% x 24.1%, p<0.001, OR=13.1). Among SPK patients, DSA+ showed a higher rate of kidney immunological loss(16.7% x 1.6%, p=0.03, OR=12.1), but a similar pancreas immunological loss and kidney, pancreas and patient survival. Among DSA+ S-PT patients, rejection occurred in 16(84.2%), being 12(63.2%) a confirmed or suspected antibody-mediated rejection (AMR). The presence of C4d+ in pancreas graft biopsies was higher among DSA+ S-PT(36.8% x 11.3%, p=0.01, OR=4.6) as was the rate of immunological graft loss(42.1% x 8.7%, p=0.001, OR=7.6), with inferior 1-year(68.4% x 96.2, p=0.001, OR=0.08) and long-term(57.9% x 91.2%, p=0.001, OR=0.13) pancreas graft survival. Mean dosage of tacrolimus(mg/kg/day) among SPK was significantly lower in DSA+ patients in 1st (0.12 x 0.18, p=0.01) and 12th month PO(0.03 x 0.08, p=0.01) and was similar among S-PT(0.14 x 0.13) in all moments. Mean level of tacrolimus(ng/ml) among SPK was similar in all moments(8.41 x 8.22) and was significantly higher in DSA+ among S-PT only in 12th month PO(10.3 x 8.2). Interestingly, long-term pancreas graft survival among S-PT patients was comparable between “weak” DSA+(MFI<1500) and DSA-(83.3% x 91.3%, respectively) which were significantly higher than DSA+(MFI>1500) S-PT(46.2%, p<0.001) patients.

Conclusion: Occurrence of post-transplant DSA was higher in S-PT than in SPK recipients, commonly triggered after a rejection episode. De novo DSA was strongly related to higher rate of rejections, AMR, C4d+ pancreatic biopsies, immunological graft failures and inferior pancreas graft survival, particularly if MFI>1500. A protocol of routine DSA monitoring could improve diagnosis and interventioning for immunological events after PT.