Adriana Zeevi, PhD, ABHI (D)
Professor of Pathology, Surgery and Immunology


Dr. Zeevi is the Director of the Tissue Typing Laboratory that provides 24 hr/ 7 day service to the solid organ and bone marrow transplant program at UPMC, VA and Children's. I provide consultation regarding the sensitization status of potential transplant candidates and their status post-transplant. In addition, I am engaged in teaching activities to graduate students, nursing staff, fellows and clinicians. I am the director of the Pathology Resident rotation and I also coordinate other fellow/clinician rotations through our clinical laboratory. I have administrative duties in relationship with the clinical tissue typing laboratory and I also serve on several Departmental committees. In addition to clinical service, I am conducting NIH funded research in collaboration with other investigators in area of my expertise of immune monitoring post-transplantation.

Office Location:
3477 Euler Way
Room 4033
Pittsburgh, PA 15213

Contact Information:
Office Phone: 412-647-6266
Fax: 412-647-6151
Email: zeevia@upmc.edu

Education

  • BA, Microbiology - 1973, Bar-llan University, Ramat-Gan, Israel
  • MS, Microbiology - 1974, Bar-llan University, Ramat-Gan, Israel
  • PhD, Microbiology - 1979, Bar-llan University, Ramat-Gan, Israel

Clinical Expertise

Dr. Zeevi's clinical expertise is in the area of Immunogenetics and Histocompatibility. I am the Clinical Director of Tissue Typing Laboratory that serves the transplant program and I provide consultation for all solid organ and bone marrow transplantation. An important aspect of my clinical expertise is to characterize the humoral sensitization and rejection in solid organ transplants. I have over 30 years of experience with immune monitoring of solid organ transplant recipients and implementation of various assays and novel approaches to evaluate the efficacy of protocols used to desensitize transplant candidates and/or to treat antibody mediated rejection in solid organ transplant recipients.

Research Interests

Pediatric Heart Transplant CTOT04 and CTOT-09 (NIH funded IRB approved)

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 1000 blood samples from 300 patients and the data is 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. We are currently analyzing the data and 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). We have obtained some promising preliminary results that were presented in two oral presentation at ISHLT in April and we are in process to write the paper.

C1-Inhibitor to Prevent Antibody Mediated Rejection (funding from CSLBehring)

We have developed an in vitro assay to predict the efficacy of C1-Inhibitor Berinert from CSL Behring. Dr Stanley Jordan and Ashley Vo from Cedar Sinai in LA had a phase I/II placebo-controlled trial of C1-Inhibitor in sensitized renal transplant recipients and we collaborated by testing the sera from those patients for C1q reactivity and confirmed that in patients that received the drug the HLA-specific C1q reactivity was inhibited. I had obtained an incoming MTA and tested blindly the samples and the results were correlated with the clinical trial. The preliminary results were presented at World transplant Congress and a paper was published in Transplantation 2015.

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 de natured 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.

Certifications

Diplomat, Laboratory Specialty of Histocompatibility Testing

Awards and Honors

  • 1982-1984 NIH New Investigator Award
  • 1984-1984 Co-Chairperson, Workshop on T Cell Cloning
  • 1989 Young Investigator's Award for Research in the Field of Histocompatibility and Immunogenetics
  • 2002-2003 President ASHI
  • 2006-2008 Member of NIH TTT Study Section
  • 2015-2017 Member of Scientific Advisory Committee IPTA

Selected Publications

View Dr. Zeevi's publications on PubMed

  • Morrell MR, Pilewski JM, Gries CJ, Pipeling MR, Crespo MM, Ensor CR, Yousem SA, D'Cunha J, Shigemura N, Bermudez CA, McDyer JF, Zeevi A. De novo donor-specific HLA antibodies ae associated with early and high-grade bronchiolitis obliterans syndrome and death after lung transplantation. J Heart Lung Transplant (Dec) 2014 33: 1288-94.
  • Zeevi A. Chronic antibody-mediated rejection: new diagnostic tools-clinical significance of C4d deposition and improved detection and characterization of human leucocyte antigen antibodies. Clin Exp Immunol (Dec) 2014 1: 52-3.
  • Ashokkumar C, Sun Q, Ningappa M, Higgs BW, Mazariegos G, Zeevi A, Sindhi R. Antithymocyte globulin facilitates alloreactive T-cell apoptosis by means of caspase-3: potential implications for monitoring rejection-free outcomes. Transplantation (Jan) 2015 99: 164-70.
  • Vo AA, Zeevi A, Choi J, Cisneros K, Toyoda M, Kahwaji J, Peng A, Villicana R, Puliyanda D, Reinsmoen N, Haas M, Jordan SC. A phase I/II placebo-controlled trial of C1-inhibitor for prevention of antibody-mediated rejection in HLA sensitized patients. Transplantation (Feb) 2015 99: 299-308.
  • Duquesnoy RJ, Kamoun M, Baxter–Lowe LA, Woodle ES, Bray RA, Claas FH, Eckels DD, Friedewald JJ, Fuggle SV, Gebel HM, Gerlach JA, Fung JJ, Middleton D, Nickerson P, Shapiro R, Tambur AR, Taylor CJ, Tinckam, Zeevi A. Should HLA mismatch acceptability for sensitized transplant candidates be determined at the high-resolution rather than the antigen level? AM J Transplant (April) 2015 15: 923-30
  • Colvin MM, Cook JL, Chang P, Francis G, Hsu DT, Kiernan MS, Kobashigawa JA, Lindenfeld J, Masri SC, Miller D, O'Connell J, Rodriguez ER, Rosengard B, Self S, White-Williams C, Zeevi A. American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology, Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, Council on Cardiovascular Disease in the Young, Council on Cardiovascular and Stroke Nursing, Council on Cardiovascular Radiology and Intervention, and Council on Cardiovascular Surgery and Anesthesia. Antibody-mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management: a scientific statement from the American Heart Association. ( May) 2015 131: 1608-39.
  • Demetris AJ, Zeevi A, O’Leary JG. ABO-compatible liver allograft antibody-mediated rejection: an update. Curr Opin Organ Transplant. (June ) 2015 20: 314-24.