Pancreas 1

Monday September 12, 2022 from 16:25 to 17:25

Room: C5

234.9 A prospective study of donor-specific anti-HLA antibody monitoring in pancreas transplantation

Ana Claudia Vidigal, Brazil

Medical Doctor
Department of Abdominal Organ Transplantation
Leforte Liberdade

Abstract

A prospective study of donor-specific anti-HLA antibody monitoring in pancreas transplantation

Ana Claudia Vidigal1, Fernanda Danziere1, Renato De Marco2, Adriana Bruscato Bortoluzzo3, Maria Kelly Venezuela3, Marcelo Perosa1.

1Department of Abdominal Organ Transplantation, Leforte Hospital, São Paulo, Brazil; 2Immunogenetic Institute and Research Incentive Funding Association, São Paulo, Brazil; 3Insper Institute of Education and Research, Statistics and Data Science, São Paulo, Brazil

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.

Presentations by Ana Claudia Vidigal



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