Beyond Histology: Lowering Human Leukocyte Antigen Antibody to Improve Renal Allograft Survival in Acute Rejection
ABSTRACT The common endpoint in the treatment of antibody-mediated rejection (AMR) is functional reversal (creatinine levels). Reduction of human leukocyte antigen (HLA) antibody strength is not commonly considered as an essential endpoint for AMR resolution. The purpose of this study was to determine whether reduction in HLA antibody intensity in patients with histologic AMR reversal influences long-term renal allograft survival.
Renal allograft recipients were included if he or she had a biopsy diagnosis of AMR (between August 2000 and October 2008) and serial evaluation for HLA antibodies prebiopsy and postbiopsy. Antibody reduction was defined as mean fluorescence intensity decrease more than 50% in highest intensity antibody after AMR therapy and the absence of new antibody formation. Patients were treated with plasmapheresis, thymoglobulin/OKT3, and corticosteroids. Survival analysis was performed using STATA/MP v10 (College Station, TX).
Twenty-eight patients were analyzed. Antibody reduction failed to occur in 22 of 28 cases. Baseline characteristics were similar between groups. Antibody nonresponders had significantly shorter allograft survival time (61.4 months) compared with antibody responders (no failures) (P=0.04, log-rank test).
In conclusion, failure to significantly reduce antibody levels and prevent new formation was strongly predictive of allograft loss. This observation suggests that the therapeutic intervention that reduces antibody production may prolong graft survival in transplantation.
- SourceAvailable from: Hanna Zielińska
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- "In addition, the profile of the donor antibodies determined before the transplantation facilitates monitoring of the production of anti-HLA antibodies after transplantation. It also helps in assessing the effectiveness of immunosuppressive therapy in the cases of humoral rejection  . Until recently, the level of allosensitization in patients on the Polish National Waiting List awaiting kidney transplantation was assessed by PRA CDC test only (Panel Reactive Antibodies Complement Dependent Cytotoxicity). "
ABSTRACT: Pretransplant identification of allosensitized patients is possible thanks to new technologies, which allow for accurate detection of clinically relevant alloantibodies. Implementation of these methods in the screening of patients awaiting transplantation increased their chance for successful donor-recipient matching. Here, 1460 patients reported to the Polish National Waiting List were screened with the Luminex Screen (LS) solid phase test for anti-HLA antibodies. The patients with detected anti-HLA antibodies were assayed with the Luminex Single Antigen (LSA) tests in order to establish defined antigen specificity of the alloantibodies. The results were compared with data on the immunization assessed with the routine complement-dependent-cytotoxicity panel-reactive-antibody assay (PRA CDC). The study showed significantly higher sensitivity of the LS method when compared with PRA CDC. It has been shown that LSA test is a useful technique identifying the specificities of alloantibodies. In particular, LSA allowed to assess donor specific antibodies (DSA) to previous mismatches (MM) and to determine acceptable HLA mismatches of the potential donors. The introduction of solid phase tests in routine pretransplant diagnostics allowed for faster and more accurate assessment of the immunological risk of the recipients and optimal donor-recipient matching. Hence, presented algorithm of solid phase assays has become a new standard for the identification of allosensitized patients awaiting kidney transplantation in Poland.Human immunology 04/2014; DOI:10.1016/j.humimm.2014.04.012 · 2.28 Impact Factor
Conference Paper: Model-based learning of segmentations[Show abstract] [Hide abstract]
ABSTRACT: A method for integrating image segmentation information into geometric models is presented. The resulting object representation has advantages of both model-based and view-based representations, in that model geometry plus learned appearance information is used to improve the prediction of object appearance over purely geometric methods. The combined models are constructed over a training set of imagery using prior geometric models. Segmentation features are matched to the geometric models, and an evidential framework is used to characterize the segmentations of model features. To test the validity of the models, a pose adjustment system was modified to incorporate the prior segmentation information. Results indicate that the inclusion of the segmentation information significantly improves pose adjustment accuracy over using purely geometric information for model appearancePattern Recognition, 1996., Proceedings of the 13th International Conference on; 09/1996
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ABSTRACT: Highly sensitized (HS) patients (>85% panel-reactive antibodies) have a lower chance of receiving a donor kidney. Within Eurotransplant the Acceptable Mismatch (AM) program was developed to increase the chances of HS patients to receive a crossmatch-negative donor kidney. The standard crossmatch in the AM program is based on complement-dependent cytotoxicity. In this study we wanted to determine the clinical relevance of human leukocyte antigen donor-directed antibodies (DDA) detected by the single antigen (SA) bead technique, in the pretransplant sera of HS patients transplanted in our center through the Eurotransplant AM program. From 34 AM patients, 27 were transplanted with 1 to 5 mismatches and 7 received a 0-mismatched graft. From the mismatched patients, retrospectively, 13 proved to possess pretransplant DDA by SA whereas 14 did not. No antibodies were found in the 0-mismatched group. Comparison of the DDA+ and DDA- patients in the human leukocyte antigen-mismatched donor/recipient combinations revealed a trend to an earlier and higher number of rejection episodes in DDA+ patients (P=0.08). No detrimental effect of DDA on graft survival was observed. This single-center study showed that in the AM program DDA detected by SA, and not by less-sensitive methods, may be related to acute rejection episodes but is not detrimental to long-term graft outcome. These findings question the increasing use of more-sensitive screening techniques for the allocation of organs.Transplantation 04/2008; 85(8):1086-90. DOI:10.1097/TP.0b013e31816b3ed1 · 3.78 Impact Factor