Frequent development of subclinical chronic antibody-mediated rejection within 1 year after renal transplantation with pre-transplant positive donor-specific antibodies and negative CDC crossmatches.

Although short-term graft survival has been improved by recent desensitization protocols including B cell depletion therapy, little is known about risk factors of chronic antibody-mediated rejection (CAMR) in HLA-incompatible (HLA-I) renal transplantation (RTx). Twenty-six HLA-I RTx with positive donor-specific antibodies (DSA) and negative T cell cytotoxic crossmatches were compared with 88 ABO-incompatible (ABO-I) and 207 ABO-identical/compatible (ABO-Id/C) RTx. The desensitization therapy consisted of mycophenolate mofetil, rituximab and double-filtration plasmapheresis. Protocol biopsies within 1 year revealed subclinical CAMR in 36% of HLA-I, 5% of ABO-I and 3% of ABO-Id/C, although clinical acute AMR was observed in 8%, 3% and 1%, respectively. The incidence of CAMR was not different between class I and class II DSA. Most of class I DSA (94%) changed to negative 1 year after RTx, whereas 77% of class II DSA remained positive. In addition, the remaining DRB ± DQB DSA caused CAMR in 80% of patients, while DQB DSA alone did not. The progress of subclinical CAMR within 1 year could not be circumvented by rituximab. Sustained class II (DRB ± DQB) DSA detection after RTx may pose a potential risk for developing CAMR, but negative change in class I DSA could also elicit CAMR.

Yamanaga S ，Watarai Y ，Yamamoto T ，Tsujita M ，Hiramitsu T ，Nanmoku K ，Goto N ，Takeda A ，Morozumi K ，Katayama A ，Saji H ，Uchida K ，Kobayashi T ... -  《-》

Significance of low-level DSA detected by solid-phase assay in association with acute and chronic antibody-mediated rejection.

We sought to clarify the controversial issue of whether detecting low-level anti-donor-specific HLA antibody (HLA-DSA) by single-antigen flow-bead assay (SAFB) may have a potential role in reducing acute and chronic antibody-mediated rejection (AMR). We retrospectively studied the preoperative serum of ABO-compatible living kidney transplantation recipients transplanted between 2001 and 2004 by SAFB using a Luminex platform. HLA-DSA was detected only by SAFB in 24 patients, although all of them showed negative T-cell and B-cell complement-dependent cytotoxicity (CDC) crossmatches. The HLA-DSA patients went on to have surprisingly high levels of acute and chronic AMR despite being only weakly sensitized (acute AMR, 33.3%; chronic AMR, 41.7%). After 2005, we implemented SAFB routinely and any patient having a positive HLA-DSA was considered to be a desensitization candidate. The 52 patients found to have HLA-DSA underwent kidney transplantation after prior treatment with a single dose of rituximab (RIT) and three or four sessions of double-filtration plasmapheresis (DFPP) in addition to regimens commonly used between 2001 and 2004. After 2005, there was a significant reduction in the occurrence of acute and chronic AMR (acute AMR, 4.7%, P < 0.001; chronic AMR, 4.7%, P < 0.001). The 5-year graft survival rate also improved after implementing SAFB (83.3-98.1%, P = 0.032). The RIT/DFPP-induction protocol may improve graft survival even in patients with low-level DSA.

Hirai T ，Kohei N ，Omoto K ，Ishida H ，Tanabe K ... -  《-》

Outcome of desensitization in human leukocyte antigen- and ABO-incompatible living donor kidney transplantation: a single-center experience in more than 100 patients.

Antibody-mediated rejection (AMR) and inferior graft outcome remain the 2 most important obstacles to successful kidney transplantation in human leukocyte antigen (HLA)- and ABO-incompatible recipients. We report a single-center experience in the outcome of desensitized living donor HLA- and ABO-incompatible kidney transplantation. Since 2007 we included 2 groups in our desensitization program. HLA-incompatible living donor kidney transplant candidates displaying donor-specific antibodies (DSA) with or without a positive T-cell and/or B-cell flow crossmatch (FCXM). Second, those displaying DSA with positive T-cell immunoglobulin (Ig)G AHG CDC CXM with a titer of ≤1:8, as well as all ABO-incompatible living donor kidney transplant candidates with an IgM isoagglutinin titer ≤ 256. They were risk stratified for AMR and underwent individualized desensitization protocol: ABO-incompatible and HLA-incompatible candidates with either positive AHG CDC CXM or positive T and/or B IgG flow CXM with repeat HLA mismatch from a previous transplantation were deemed to be high risk and received a single dose of Rituximab, therapeutic plasma exchange and high-dose intravenous immunoglobulin (IVIG) (2 g/kg). HLA-incompatible candidates with negative CDC but positive T and/or B IgG FCXM were deemed intermediate risk, receiving rituximab and high-dose IVIG. Those with positive DSA but negative flow and CDC CXM were deemed low risk, receiving low-dose IVIG (1 g/kg). All patients received induction with thymoglobulin and were maintained on a tacrolimus-based immunosuppressive regimen. Among 124 incompatible recipients, 85 received HLA-incompatible and 39 ABO-incompatible living donor kidney transplantations after desensitization. Risk stratification for HLA-incompatible transplants revealed 61 high-risk, 42 intermediate-risk, and 21 low-risk cases. Ninety-nine (80%) were primary transplants. At a median follow-up of 23 (range 1-53) months, patient survival was 98% and death censored graft survival 96%. Mean serum creatinine was 84 μmol/L (range 41-169). Acute cellular rejection was observed in 15 (12%) and AMR in 5 (4%) patients. All rejection episodes responded to treatment except 1 AMR in an ABO-incompatible transplant that led to graft failure. Our risk stratification for desensitization strategy achieved a low incidence of AMR among HLA- and ABO-incompatible kidney transplant recipients. Their 2-year data appear to be comparable to HLA- and ABO-compatible transplantations.

Al Meshari K ，Pall A ，Chaballout A ，El Gamal H ，Al Mana H ，Humaidan H ，Alzayer F ，Al Talhi M ... -  《-》

Treatment of Biopsy-Proven Acute Antibody-Mediated Rejection Using Thymoglobulin (ATG) Monotherapy and a Combination of Rituximab, Intravenous Immunoglobulin, and Plasmapheresis: Lesson Learned from Primary Experience.

Zheng J ，Xue W ，Qing X ，Jing X ，Hou J ，Tian X ，Guo Q ，He X ，Cai J ... -  《-》

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 ... -  《-》