Impact of alloantibody strength in crossmatch negative DSA positive kidney transplantation.

The clinical relevance of pre-transplant "low-level" donor specific anti-HLA antibodies (DSAs) in crossmatch negative kidney transplant recipients remains unclear. To determine what level of DSA associates with antibody mediated rejection (AMR) could be the way to measure the clinical relevance of pre-transplant "low-level" donor specific anti-HLA antibodies (DSAs) in crossmatch negative kidney transplant recipients. A retrospective analysis of 221 patients from October 2008 to December 2009 was included in this study. Sera were obtained pre-transplant and two weeks post-transplant and tested for DSA using LABScreen single antigen beads. Among the 221 patients, 11 experienced AMR within 200days after transplant (5%). Pre-transplant DSA was associated with AMR at multiple mean fluorescence intensity (MFI) cutoffs (500, 1000, 2000, 3000, 5000; p=0.003, 0.001, 0.007, 0.003, and 0.003, respectively). No correlation was seen between acute T-cell mediated rejection (CMR) and pre-transplant DSA at any of the same MFI cutoffs. There was an increased risk of AMR with higher levels of pre-transplant DSA. Finally, an increase in DSA MFI from pre- to two weeks post-transplant was indicative of a higher probability of AMR. Overall, this data supports using the single antigen bead to detect "low-level" DSA both pre- and post- as having a positive and persistent DSA may be predictive of higher AMR rates and poorer graft survival.

Wu P ，Jin J ，Everly MJ ，Lin C ，Terasaki PI ，Chen J ... -  《-》

Analysis of preformed donor-specific anti-HLA antibodies characteristics for prediction of antibody-mediated rejection in kidney transplantation.

The relevance of preformed donor specific antibodies (DSA) detected by Luminex assays, with a negative complement-dependent cytotoxicity (CDC) crossmatch, remains unsettled in kidney transplantation (KT). We aimed to analyze the impact of preformed DSA characteristics on kidney graft outcomes. In 462 patients that received a kidney graft in our unit, between 2007 and 2012, pre-transplant sera were analyzed by Luminex screening assay to determine the presence of anti-human leukocyte antigen (HLA) antibodies and single-antigen bead assay [positive if mean fluorescence intensity (MFI) ≥ 1000] to assign anti-HLA specificities. Anti-HLA antibodies were present in 95 patients (20.6%), but only 40 (8.7%) had DSA. Antibody-mediated rejection (AMR) at 1-year was higher in patients with DSA (35.0%) than in those without them (0.9%) (P < 0.001). Only DSA with a MFI of >3000 were significantly associated with AMR occurrence. Receiver operator curves revealed that a MFI of >4900 in the highest DSA bead had a high sensitivity (85.7%) and that the sum of all DSA beads MFI > 11,000 had a high specificity (92.3%) for AMR prediction. Anti-thymocyte globulin versus basiliximab induction was more frequent in DSA+ AMR- (65.4%) versus DSA+ AMR+ (34.6%) patients (P = 0.072). Five-year censored graft survival was lower in DSA+ than in DSA- patients (respectively, 84.8% versus 94.9%, P = 0.006), although survival was only reduced in DSA+ AMR+ (68.8%) versus DSA+ AMR- (96.0%) patients (P = 0.038). Preformed DSA is associated with kidney graft loss, in relation with AMR occurrence. DSA strength may be used to improve immunological risk stratification of sensitized patients and their clinical management.

Malheiro J ，Tafulo S ，Dias L ，Martins LS ，Fonseca I ，Beirão I ，Castro-Henriques A ，Cabrita A ... -  《-》

Effect of pretransplant human leukocyte antigen antibodies detected by solid-phase assay on heart transplant outcomes.

The significance of pretransplant human leukocyte antigen antibodies (HLA-Abs), especially donor-specific HLA-Abs (DSA), as detected by single antigen bead assay (SAB), is not well characterized in cardiac transplantation (CTX). We analyzed the significance of DSA detected by SAB in predicting crossmatch (XM) results and post-transplant rejection. We performed a retrospective study of 85 CTX with negative cytotoxicity XM. We tested pretransplant sera collected within 24 hours of transplantation by flow cytometric XM (FXM) and SAB. DSA identified by SAB were utilized to perform a virtual crossmatch (VXM). Positive VXM was defined as the presence of DSA at mean fluorescence intensity (DMFI)>1500. Additionally, to analyze the significance of low-level DSA weakly positive VXM was DMFI 300 to 1500. We defined a negative VXM as MFI<300. VXM results were correlated with FXM results and with posttransplant rejection. Patients in the weakly positive and negative VXM had similar posttransplant rejections. DMFI>1500 correlates well with FXM results (accuracy=90%). Patients with DMFI>1500 had a higher incidence of antibody-medicated rejection (AMR; P=.0052), AMR grade I (P<.0001), cell-mediated rejection (CMR) grade>1R/1A (P=.018), and CMR grade>2R/3A (P=.057). Similarly patients with positive FXM had a higher incidence of AMR (P=.091), AMR grade 1 (P<.0001), CMR grade>1R/1A (P=.05), and CMR grade>2R/3A (P=.56). In conclusion, SAB defined DMFI>1500 can be used as a surrogate for FXM. Recipients with DMFI>1500 pretransplant and positive FXM have significantly higher rates of AMR and CMR compared to recipients with DMFI<1500 or negative FXM.

Gandhi MJ ，DeGoey SR ，Bundy K ，Kremers WK ，Knauer R ，Pereira N ，Edwards B ，Kushwaha S ，Daly RC ... -  《-》

Preformed complement-activating low-level donor-specific antibody predicts early antibody-mediated rejection in renal allografts.

Lawrence C ，Willicombe M ，Brookes PA ，Santos-Nunez E ，Bajaj R ，Cook T ，Roufosse C ，Taube D ，Warrens AN ... -  《-》

Characteristics of donor-specific anti-HLA antibodies and outcome in renal transplant patients treated with a standardized induction regimen.

Pre-transplant donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have been associated with antibody-mediated rejection (AMR) and early kidney allograft loss. Uncertainties remain regarding the general applicability of these findings and the optimal induction therapy in DSA-positive patients. Pre-transplant sera from 174 patients receiving a crossmatch-negative kidney transplant were retrospectively analysed for DSA using Luminex technology. DSA with mean-fluorescence intensity (MFI) values above 500 were considered positive. All recipients received basiliximab induction and tacrolimus-based maintenance immunosuppression. DSA were monitored post-transplantation in patients with pre-transplant DSA. Antibody results were correlated with the incidence of rejection and graft loss. In total, 61/174 patients had pre-transplant DSA. We found a strong correlation between the presence of DSA against class I and II HLA and DSA MFI greater than 10 000. Both DSA patterns independently predicted an increased risk of early AMR (odds ratio 4.24 and 4.75, respectively, P < 0.05). The risk for AMR in patients with intermediate MFI (3000-10 000) gradually increased with increasing MFI but group sizes were too small to allow for final conclusions. The risk for AMR was comparable to nonsensitized patients in patients with only class I or II HLA-DSA or MFI below 3000. 5-year allograft survival was lowest in patients with simultaneous presence of class I and II HLA-DSA and MFI above 10 000 (45%) but was comparable between patients with only HLA class I or II or no DSA (90.0, 90.0 and 88.1%, respectively). AMR was the only independent predictor of graft loss. Undetectable DSA 14 days post-transplant predicted excellent long-term outcome. . The favourable outcome in the majority of DSA-positive patients despite non-depleting antibody induction and the poor outcome in patients with class I and II HLA-DSA and high DSA strength call for a differentiated therapeutic approach in this patient population.

Zecher D ，Bach C ，Staudner C ，Böger CA ，Bergler T ，Banas B ，Spriewald BM ... -  《-》