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Clinical Outcomes of Lung Transplantation in the Presence of Donor-Specific Antibodies.

ABSTRACT: Rationale: There is significant variation in approach to pre-lung transplant donor-specific antibodies (DSA), with some centers declining to cross any DSA. We implemented a protocol for transplantation for candidates with pretransplant DSA so long as a prospective complement-dependent cytotoxicity crossmatch was negative, regardless of number, specificity, class, or mean fluorescence intensity.Objectives: To compare post-transplant outcomes including overall survival, chronic lung allograft dysfunction-free survival, antibody-mediated rejection, and acute cellular rejection in lung transplant recipients where pretransplant DSA was and was not present.Methods: This was a single-center retrospective cohort study. For recipients with pretransplant DSA, if the prospective complement-dependent cytotoxicity crossmatch was negative, the donor offer was accepted and plasmapheresis was performed within 24 hours of transplantation and continued until retrospective crossmatch results returned. Immunosuppression and post-transplant management were not otherwise modified.Results: Of the 203 included recipients, 18 (8.9%) had pretransplant DSA. The median DSA mean fluorescence intensity was 4,000 (interquartile range, 2,975-5,625; total range, 2,100-17,000). The median number of DSA present per patient was one (interquartile range, 1-2). The presence of pretransplant DSA was not associated with increased mortality (hazard ratio, 1.2; 95% confidence interval [CI], 0.4-3.4) or decreased chronic lung allograft dysfunction-free survival (hazard ratio, 1.1; 95% CI, 0.6-2.1). Recipients with pretransplant DSA were more likely to require prolonged mechanical ventilation (adjusted odds ratio, 7.0; 95% CI, 2.3-21.6) and to have antibody-mediated rejection requiring treatment (adjusted odds ratio, 7.5; 95% CI, 1.0-55.8).Conclusions: A protocol of accepting donor offers for lung transplant candidates with preformed, complement-dependent cytotoxicity crossmatch-negative DSA is associated with increased need for prolonged mechanical ventilation and antibody-mediated rejection without affecting short-term overall or chronic lung allograft dysfunction-free survival.

SUBMITTER: Courtwright AM

PROVIDER: S-EPMC6850801 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and objectivesThe prognostic value of preformed donor-specific HLA antibodies (DSA), which are only detectable by sensitive methods, remains controversial for kidney transplantation.Design, setting, participants, & measurementsThe outcome of 4233 consecutive kidney transplants performed between 2012 and 2015 in 18 German transplant centers was evaluated. Most centers used a stepwise pretransplant antibody screening with bead array tests and differentiation of positive samples by single antigen assays. Using these screening results, DSA against HLA-A, -B, -C, -DRB1 and -DQB1 were determined. Data on clinical outcome and possible covariates were collected retrospectively.ResultsPretransplant DSA were associated with lower overall graft survival, with a hazard ratio of 2.53 for living donation (95% confidence interval [95% CI], 1.49 to 4.29; P<0.001) and 1.59 for deceased donation (95% CI, 1.21 to 2.11; P=0.001). ABO-incompatible transplantation was associated with worse graft survival (hazard ratio, 2.09; 95% CI, 1.33 to 3.27; P=0.001) independent from DSA. There was no difference between DSA against class 1, class 2, or both. Stratification into DSA <3000 medium fluorescence intensity (MFI) and DSA ≥3000 MFI resulted in overlapping survival curves. Therefore, separate analyses were performed for 3-month and long-term graft survival. Although DSA <3000 MFI tended to be associated with both lower 3-month and long-term transplant survival in deceased donation, DSA ≥3000 MFI were only associated with worse long-term transplant survival in deceased donation. In living donation, only strong DSA were associated with reduced graft survival in the first 3 months, but both weak and strong DSA were associated with reduced long-term graft survival. A higher incidence of antibody-mediated rejection within 6 months was only associated with DSA ≥3000 MFI.ConclusionsPreformed DSA were associated with an increased risk for graft loss in kidney transplantation, which was greater in living than in deceased donation. Even weak DSA <3000 MFI were associated with worse graft survival. This association was stronger in living than deceased donation.

Project description:Due to the current organ shortage, living donor kidney transplantation is increasingly performed across HLA (human leukocyte antigen) or ABO antibody barriers. There is still uncertainty about the risk of antibody-mediated rejection (AMR) episodes, which may limit long-term graft survival. From March 2007 to December 2016, 58 sensitized living donor kidney transplant candidates were identified and 38 patients eventually included in the study: 36 patients (95%) had pre-transplant and pre-desensitization Luminex-detected donor-specific HLA antibodies (DSA), and 17/36 patients (47%) in addition had a positive crossmatch result. Two patients had no detectable DSA but a positive CDC B-cell crossmatch result. Patients were treated with pre- and post-transplant apheresis and powerful immunosuppression including the anti-CD20 antibody rituximab (N = 36) in combination with thymoglobulin (N = 20) or anti-IL2 receptor antibody (N = 18). The results of the 38 successfully desensitized and transplanted patients were retrospectively compared to the results of 76 matched standard-risk recipients. Desensitized patients showed patient and graft survival rates similar to that of standard-risk recipients (P = 0.55 and P = 0.16, respectively). There was a trend toward reduced death-censored graft survival in desensitized patients (P = 0.053) which, however, disappeared when the 34 patients who were transplanted after introduction of sensitive Luminex testing were analyzed (P = 0.43). The incidence of rejection episodes without borderline changes were in desensitized patients with 21% similar to the 18% in standard-risk patients (P = 0.74). Thirty-six patients had pre-transplant HLA class I and/or II DSA that were reduced by 85 and 81%, respectively, during pre-transplant desensitization (P < 0.001 for both). On day 360 after transplantation, 20 of 36 (56%) patients had lost their DSA. The overall AMR rate was 6% in these patients, but as high as 60% in 5 (14%) patients with persistent and de novo DSA during year 1; 2 (40%) of whom lost their graft due to AMR. Eleven (31%) patients with persistent DSA but without de novo DSA had an AMR rate of 18% without graft loss while one patient lost her graft without signs of AMR. Our desensitization protocol for pre-sensitized living donor kidney transplant recipients with DSA resulted in good graft outcomes with side effects and rejection rates similar to that of standard-risk recipients. Adequate patient selection prior to transplantation and frequent immunological monitoring thereafter is critical to minimize rejection episodes and subsequent graft loss.

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Clinical Outcomes of Lung Transplantation in the Presence of Donor-Specific Antibodies.

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