Adriana Zeevi, PhD, ABHI (D)

Pediatric Heart Transplant CTOT04

I am the director of the Alloantibody Core for pediatric heart transplant CTOT-04 project "Alloantibodies in Cardiac Transplantation-Intervention, Outcomes and Mechanisms – (PI - Dr. Steve Webber). We have completed testing on over 2000 blood samples from 300 patients and the data was transferred on the NIH site for further analysis of various aspects related to clinical outcomes. The primary endpoint is freedom from death, re-transplantation and rejection with hemodynamic compromise. Data analysis and paper preparation. Several talks were presented at ATC 2016.

Pediatric Heart Transplant CTOT-09 (NIH funded IRB approved)

We continue enrolling patients and following previous patients under the CTOT-09 (PI - Dr. Steve Webber). In addition to HLA-Antibodies in the new grant we are interested (in collaboration with Dr. Mohanakumar from Saint Louis) on the impact of non-HLA antibodies in a large cohort of pediatric heart transplant recipients. We continue the data entry and the plan to have the first study on prevalence of HLA and non HLA Ab in the cohort vs. various patient demographic data.

T and B Homeostasis After Induction Therapy in Kidney Transplantation (NIH funded IRB approved, PI Dr. F Lakkis)

In collaboration with Starzl Institute (Dr. Fadi Lakkis PI) I am participating in an NIH funded project evaluating the difference between two depletion protocols on renal transplant recipients. Dr. Diana Metes group presented at the World transplant Congress our collective findings: the presence of donor specific HLA antibody was correlated with a certain T helper cell subset. We continue our collaboration of characterizing the antibody specificity and function in supernatants of co-cultures of T helper and B cells from renal transplant recipients. Presently Dr. Metes is summarizing the data for a publication.

Donor-specific HLA Antibodies (DSA) in Pediatric Liver Transplant Recipients

In collaboration with Drs. Gheeta Chalasani and George Mazariegos we are evaluating B cell subsets, T cell subsets and DSA in pediatric liver transplant recipients who were off successfully of immunosuppression, in the process of weaning and who either failed weaning or maintained on immunosuppression. Preliminary results were presented by Dr. Chalasani's group at the World Transplant Congress and also at the liver meeting in July 2015. Dr. Chalasani is planning to summarize and publish the study. We demonstrated that the donor specific HL-Ab (DSA) in the tolerant group had a lower level and were non-complement binding as opposed to DSA in the liver transplant recipients on immunosuppression (higher level and C1q binding).

Non-HLA Antibodies in Lung Transplant Recipients

In collaboration with Drs. John McDyer and Chris Ensor (Pulmonary Division University of Pittsburgh) and Dr. Nancy Reinsmoen (Cedar Sinai), we are interested in non-HLA antibodies in lung transplant recipients. In collaboration with Dr. Reinsmoen we tested 5 non-HLA antibodies including Anti-Angiotensin type 1 receptor (AT1R), Endothelin (ETAR), Perlacan, Collagen V and Vimentin. The paper was submitted and accepted to JHLT 2016.

The Frequency and distribution of HLA-Ab in various IgG preparations (funding from CSL Behring)

We received 30 preparations of IgG that are used for in vivo infusion and we tested for the HLA-Ab presence , strength by dilution and C1q binding. We also determined that many preparations contain denatured HLA-Ab that can bind on the Luminex platform and give false positive results. We applied a special acid treatment on the Luminex beads that allows us to uncover which of the HLA-Ab tested on the regular beads are against real epitopes and which are against denatured HLA. A large proportion of positive beads were identified to detect denatured HLA molecules that in vivo do not have a clinical significance. The abstract will be presented (poster) at ASHI in September 2016. The study summary and publication preparation are in progress.

IgG subtype and C1q activity for risk assessment in kidney transplant recipients

We continue the collaboration with Drs. Carmen Lefaucheur, Dennis Glotz, Alex Loupy and the group from France to evaluate the clinical significance of all the antibody parameters and a new publication was accepted in the Journal of the American Society of Nephrology.

Proteosome Inhibitor Carfilzomib (CFZ) based therapy for antibody mediated rejection in lung transplant recipients

In collaboration with Pulmonary group and Dr. Chris Ensor we summarized the experience with CFZ therapy in 16 lung transplant recipients and the paper will be submitted in July 2016. We also received funding from Amgen Inc. to continue the studies of CFZ in 20 lung transplant patients with antibody mediated rejection.

Liver Biology

I am participating at weekly meetings with Dr. Demetris' group discussing various projects regarding liver biology and impact of various drugs on the expression of MHC antigens on liver endothelium.