The strength of donor-specific antibody is a more reliable predictor of antibody-mediated rejection than flow cytometry crossmatch analysis in desensitized kidney recipients.

The aim of this study was to evaluate the utility of donor-specific antibodies (DSA) and flow cytometry crossmatch (FCCM) as tools for predicting antibody-mediated rejection (AMR) in desensitized kidney recipients. Sera from 44 patients with DSA at the time of transplant were reviewed. Strength of DSA was determined by single antigen Luminex bead assay and expressed as mean fluorescence intensity (MFI). T- and B-cell FCCM results were expressed as mean channel shift (MCS). AMR was diagnosed by C4d deposition on biopsy. Incidence of early AMR was 31%. Significant differences in the number of DSAs (p = 0.0002), cumulative median MFI in DSA class I (p = 0.0004), and total (class I + class II) DSA (p < 0.0001) were found in patients with and without AMR. No significant difference was seen in MCS of T and B FCCM (p = 0.095 and p = 0.307, respectively). The three-yr graft survival in desensitized patients with DSA having total MFI < 9500 was 100% compared to 76% with those having total MFI > 9500 (p = 0.022). Desensitized kidney transplant recipients having higher levels of class I and total DSA MFI are at high risk for AMR and poor graft survival. Recipient DSA MFI appears to be a more reliable predictor of AMR than MCS of FCCM.

Mujtaba MA ，Goggins W ，Lobashevsky A ，Sharfuddin AA ，Yaqub MS ，Mishler DP ，Brahmi Z ，Higgins N ，Milgrom MM ，Diez A ，Taber T ... -  《-》

Acceptable donor-specific antibody levels allowing for successful deceased and living donor kidney transplantation after desensitization therapy.

Reinsmoen NL ，Lai CH ，Vo A ，Cao K ，Ong G ，Naim M ，Wang Q ，Jordan SC ... -  《-》

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 ... -  《-》

Pre-transplant donor specific anti-HLA antibody is associated with antibody-mediated rejection, progressive graft dysfunction and patient death.

The long term effect of donor specific antibodies (DSA) detected by Luminex Single Antigen Bead (SAB) assay in the absence of a positive complement-dependant cytotoxicity (CDC) crossmatch is unclear. DSA at the time of transplant were determined retrospectively in 258 renal transplant recipients from 2003 to 2007 and their relationship with rejection and graft function prospectively evaluated. After a median of 5.6 years follow-up 9% of patients had antibody mediated rejection (AMR) (DSA 11/37 (30%), DSA-Neg 13/221 (6%), HR 6.6, p<0.001). Patients with anti-HLA class II (HR 6.1) or both class I+II (HR 10.1) DSA had the greatest risk for AMR. The Mean Fluorescent Intensity (MFI) of the DSA was significantly higher in patients with AMR than those with no rejection (p=0.006). Moreover, the strength of the antibody was shown to be important, with the risk of AMR significantly greater in those with DSA >8000 MFI than those with DSA <8000 MFI (HR 23, p<0.001). eGFR progressively declined in patients with DSA but was stable in those without DSA (35.7 ± 20.4 mls/min vs 48.5 ± 22.7) and composite patient and graft survival was significantly worse in those with class II (HR 2.9) or both class I+II (HR 3.7) but not class I DSA. Class II DSA alone, or in combination with class I DSA had the strongest association with graft loss and patient death. Patients with DSA not only have increased rates of acute AMR, but also chronic graft dysfunction, graft loss and death. Antibody burden quantified by SAB assay may identify patients at highest immunological risk and therefore influence patient management and improve long-term patient outcome.

Fidler SJ ，Irish AB ，Lim W ，Ferrari P ，Witt CS ，Christiansen FT ... -  《-》

Relevance of different antibody detection methods for the prediction of antibody-mediated rejection and deceased-donor kidney allograft survival.

Vlad G ，Ho EK ，Vasilescu ER ，Colovai AI ，Stokes MB ，Markowitz GS ，D'Agati VD ，Cohen DJ ，Ratner LE ，Suciu-Foca N ... -  《-》