J.J. Teuteberg

Persistent strong anti-HLA antibody at high titer is complement binding and associated with increased risk of antibody-mediated rejection in heart transplant recipients

BACKGROUND Sensitized heart transplant candidates are evaluated for donor-specific anti-HLA IgG antibody (DSA) by Luminex single-antigen bead (SAB) testing (SAB-IgG) to determine donor suitability and help predict a positive complement-dependent cytotoxicity crossmatch (CDC-XM) by virtual crossmatching (VXM). However, SAB testing used for VXM does not correlate perfectly with CDC-XM results and individual transplant programs have center-specific permissible thresholds to predict crossmatch positivity. A novel Luminex SAB-based assay detecting C1q-binding HLA antibodies (SAB-C1q) contributes functional information to SAB testing, but the relationship between SAB strength and complement-binding ability is unclear. METHODS In this retrospective study, we identified 15 pediatric and adult heart allograft candidates with calculated panel-reactive antibody (cPRA) >50% by SAB-IgG and compared conventional SAB-IgG results with SAB-C1q testing. RESULTS Pre- and post-transplant DSA by SAB-C1q correlated with DSA by SAB-IgG and also with CDC-XM results and early post-transplant endomyocardial biopsy findings. Individual HLA antibodies by SAB-IgG in undiluted sera correlated poorly with SAB-C1q; however, when sera were diluted 1:16, SAB-IgG results were well correlated with SAB-C1q. In some sera, HLA antibodies with low mean fluorescent intensity (MFI) by SAB-IgG exhibited high SAB-C1q MFIs for the same HLA antigens. Diluting or heat-treating these sera increased SAB-IgG MFI, consistent with SAB-C1q results. In 13 recipients, SAB-C1q-positive DSA was associated with positive CDC-XM and with early clinical post-transplant antibody-mediated rejection (cAMR). CONCLUSIONS Risk assessment for positive CDC-XM and early cAMR in sensitized heart allograft recipients are correlated with SAB-C1q reactivity.

Cancer-Free Survival Following Alemtuzumab Induction in Heart Transplantation

BACKGROUND The malignancy rate after alemtuzumab (C-1H) induction in cardiac transplantation is unknown. METHODS A retrospective analysis from a single center for all patients that underwent cardiac transplantation from January 2000 to January 2011 and that had no history of malignancy before transplantation was performed. Patients induced with alemtuzumab were compared with a group of patients receiving thymoglobulin or no induction and assessed for 4-year cancer-free post-heart transplantation survival. RESULTS Of 402 patients included, 185 (46.0%) received alemtuzumab, 56 (13.9%) thymoglobulin, and 161 (40.0%) no induction. Baseline characteristics did not differ between groups: mean age 54.0 years, male 77.1%, white 88.6%, ischemic cardiomyopathy 49.0%. The calcineurin inhibitor was tacrolimus in 98.9% of alemtuzumab patients, 98.2% of thymoglobulin patients, and 87.0% of the noninduced (P < .001). The secondary agent was mycophenolate mofetil in all but 16 noninduced patients (9.9%), who received azathioprine. The 4-year cancer-free survival did not differ between groups: 88.1% alemtuzumab, 87.5% thymoglobulin, 88.2% noninduction; P = .088. The 4-year nonskin cancer-free survival was 96.8% for the alemtuzumab group, 96.4% for the thymoglobulin group, and 95.7% for the noninduced; P = .899. CONCLUSIONS Neither the 4-year cancer-free survival nor the 4-year nonskin cancer-free survival differed between the alemtuzumab, thymoglobulin, and noninduced groups.