Browsing by Author "Beiras-Fernandez, Andres"

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Donor-Specific HLA Alloantibodies: Long-Term Impact on Cardiac Allograft Vasculopathy and Mortality After Heart Transplant
(Başkent Üniversitesi, 2008-09) Kaczmarek, Ingo; Ueberfuhr, Peter; Spannagl, Michael; Reichart, Bruno; Sodian, Ralf; Vicol, Calin; Schmoeckel, Michael; Beiras-Fernandez, Andres; Kauke, Teresa; Deutsch, Marcus-André
Objectives: The clinical significance of anti-HLA-alloantibodies remains controversial. Recent studies have linked development of donor-specific HLA-antibodies to chronic allograft rejection and graft loss after heart, kidney, and lung transplants. We investigated the clinical impact of donor-specific humoral alloreactivity during the follow-up of heart transplant recipients. Patients and Methods: The sera of 213 heart transplant recipients were screened by enzyme-linked immunosorbent assay for HLA-antibody production. The antigen specificity of the detected HLA class I and class II antibodies was identified using a Luminex assay. Outcome variables were survival, cardiac allograft vasculopathy, and cellular rejection. Results: The cumulative incidence of alloantibody formation was 23/213 patients (10.8%). The majority of detected alloantibodies were donor-specific for HLA class II. Mean follow-up at antibody measurements was 7 ± 4.9 years. Freedom from vasculopathy at 5 and 10 years was 77.9% and 26% in donor-specific HLA-antibody-positive patients compared with 84.6% and 65.2% in antibody-negative controls (P = .025). Freedom from treated, biopsy-proven rejection was 44.4% for donor-specific HLA-antibody-positive patients compared with 70.2% in the controls (P = .06). Multivariate analyses identified donor-specific HLA antibody positivity as an independent risk factor for vasculopathy. Conclusions: Our results demonstrate a strong correlation between the development of donor-specific HLA antibodies and adverse outcomes after heart transplant. Detection of donor-specific HLA antibodies might identify high-risk patients and offer an opportunity for early clinical intervention and modification of immunosuppression.
In Vitro Influence of Polyclonal Anti-Thymocyte Globulins on Leukocyte Expression of Adhesion Molecules
(Başkent Üniversitesi, 2005-12) Beiras-Fernandez, Andres; Walther, Sebastian; Kaczmarek, Ingo; Ngo, Truc; Muenzing, Silvia; Hammer, Claus; Thein, Eckart
Objectives: Polyclonal anti-thymocyte globulins (ATGs) are drugs used in the induction of immunosuppression, in the treatment of acute rejection, and in the therapy of hematologic disorders. Treatment with ATGs can produce adverse effects due to cross-reacting antibodies directed against nonmyeloid cells. This study sought to evaluate the interaction of ATGs and some adhesion molecules expressed on the surface of neutrophils and lymphocytes. Materials and Methods: We determined the effects of different doses of 3 polyclonal ATGs on the activation and expression of lymphocyte and neutrophil adhesion molecules in whole blood by means of flow cytometry. Results: ATG treatment reduced the percentage of lymphocytes gated for CD18 and CD62L, as well as the expression of CD11b, CD18, and CD62L in a dose-dependent manner. ATGs modulated the percentage of gated neutrophils for CD18. Although ATG treatment did not affect CD11b or CD62L gating in neutrophils, it did regulate expression of these adhesion markers. Conclusions: Our results show that ATGs can modify the expression levels of some of the main leukocyte adhesion molecules that are responsible for the characteristic cellular adhesion after ischemia/ reperfusion. These properties of ATGs may contribute to reduced leukocyte infiltration after solid-organ transplantation.
Influence of Hypothermia and Cardioplegic Solutions on Expression of α-Gal Epitope on Porcine Aortic Endothelial Cells
(Başkent Üniversitesi, 2010-09) Keller, Miriam; Brenner, Paolo; Reichart, Bruno; Schmoeckel, Michael; Beiras-Fernandez, Andres
bjectives: The Galα1-3Galβ1-4GlcNAc-R is the major antigen on pig tissue bound by human xenoreactive natural antibodies in xenotransplant. We have investigated in vitro the influence of hypothermic storage with cardioplegic solutions on expression of Galα1-3Galβ1-4GlcNAc-Rs and hyperacute xenograft rejection. Materials and Methods: To analyze effects of hypothermia on the Galα1-3Galβ1-4GlcNAc-Rs, cultured porcine aortic endothelial cells were exposed to a temperature of 4°C for 1 hour, 4 hours, and 6 hours. Cell cultures of the control groups were incubated at the same time at 38°C. To investigate the influence of cardioplegic solutions on the Galα1-3Galβ1-4GlcNAc-Rs, porcine aortic endothelial cells were exposed to 4°C for 4 hours in the presence of University of Wisconsin solution or histidine-tryptophan-ketoglutarate solution. Cells of the control groups were cooled at 4°C for 4 hours without cardioplegic solution. After treatment, porcine aortic endothelial cells were submitted to fluorescence-activated cell sorter. Results: Hypothermia of 4°C showed no significant effect on the quantity of Galα1-3Galβ1-4GlcNAc-Rs. However, the treatment of porcine aortic endothelial cells with University of Wisconsin solution resulted in a highly significant reduction of Galα1-3Galβ1-4GlcNAc-Rs by 50% (P = .006). Treatment of porcine aortic endothelial cells with histidine-tryptophan-ketoglutarate solution decreased α-Gal quantity significantly by 32% (P = .011). Conclusions: Our data offer new perspectives in the prevention of hyperacute, humoral xenograft rejection by reducing the Galα1-3Galβ1-4GlcNAc-Rs after exposure to different cardioplegic solutions.
Novel Treatment with Rituximab of Oropharyngeal Posttransplant Lymphoproliferative Disorder after Heart Transplantation
(Başkent Üniversitesi, 2005-12) Kaczmarek, Ingo; Beiras-Fernandez, Andres; Sadoni, Sebastian; Bengel, Dominik; Deutsch, Marcus-Andre; Meiser, Bruno; Reichart, Bruno
Posttransplant lymphoproliferative disorders are severe complications that arise after solid organ transplantation, which are often related to Epstein-Barr virus. Reports are anecdotal, and a standardized therapy does not exist. We report a case of a 36-year-old man who developed posttransplant lymphoproliferative disorder of the oropharynx 1 year after receiving a heart transplant. A short review of the literature is presented, after which a new therapeutic approach that combines antiviral therapy, monoclonal antibodies, and a sirolimus-based maintenance immunosuppression regimen with reduced target trough levels of tacrolimus is introduced. The patient achieved complete remission and was free from recurrence 18 months after the therapy was initiated.
Off-Pump Coronary Surgery for Allograft Vasculopathy 8 Years After Heart Transplant
(Başkent Üniversitesi, 2009-12) Michel, Sebastian; Vicol, Calin; Reichart, Bruno; Abicht, Jan; Ueberfuhr, Peter; Beiras-Fernandez, Andres; Kaczmarek, Ingo
Cardiac allograft vasculopathy is a severe complication after heart transplant, and is the major cause of death in patients surviving 1 year after transplant. We present a 59-year-old patient undergoing off-pump, coronary artery bypass surgery, 8 years after heart transplant. Owing to toxic liver disease, the lipid lowering therapy with statins had to be stopped 6 years after transplant, and coronary artery disease developed rapidly within 2 years. Off-pump, coronary bypass surgery was performed using a new, multisuction cardiac positioner; a disposable stabilizer; and a proximal seal system to avoid clamping of the aorta. The patient received 3 bypass grafts: the left internal thoracic artery; to the left anterior descending coronary artery; 1 saphenous vein graft to the marginal branch of the circumflex artery; and 1 saphenous vein graft to the right coronary artery. His postoperative course was uneventful.