Role of non-HLA antibodies in the early failure of pediatric renal transplants
Renal transplantation represents the ideal treatment option for children in terminal kidney failure. However, in half of the cases graft survival will not reach 20 years. Several immunological and non-immunological reasons underlie such a premature organ failure and antibody-mediated rejection is the first cause of graft loss after the first year. Whilst anti-HLA antibodies are the primary cause of antibody-mediated rejection, recently other, non-HLA antibodies have been identified. At this stage, the detrimental role on graft survival of anti-AT1R antibodies has been demonstrated both in pediatric and adult renal transplantation, whilst the potential harmful role of anti-ETAR antibodies remains purely speculative. In this light, using biological specimens (blood samples and biopsies) from a unique cohort of >150 patients from two major pediatric transplant centers, this translational study will unequivocally assess the possible causative role of anti-ETAR immunity in premature pediatric renal transplant failure.
Collaborators: Elisa Benetti, Luisa Murer, Marco Spada, Luca dello Strologo, Padua University Hospital, Bambino Gesù Hospital (Rome) and IRP
Cell transplantation therapies in the treatment of neurodegenerative disorders
Chronic neurological disorders encompass a number of diseases affecting the functionality of various areas of the central nervous system, whose incidence is expected to rise with increased life expectancy. A potentially promising approach to the treatment of such diseases is represented by the application of cell transplantation therapies with the aim to replace, repair or regenerate injured areas, or to modulate and dim the inflammatory processes possibly associated. Over the years our group has developed a tremendous expertise in this research area, particularly in the context of both Parkinson’s and Huntington’s disease (HD). We have contributed to the progress in this field with the development of challenging preclinical models in primates and have set up assays to enable the fine monitoring of the cellular and humoral immune responses following neural cell transplantation in such models. Currently we are also involved in the design of a new UK-based clinical trial regarding transplantation of human neural precursors in a cohort of patients with HD.
Collaborators: Philippe Hantraye, Romina Aron Badin, Padua University Hospital and CEA Neurodegenerative Diseases Laboratory, Fontenay-aux-Roses (Parigi),
Autoimmune responses and Covid-19
Our group has always been very interested in the management of the immune response following solid organ transplantation. Recently we have been involved in the care of transplant recipients who developed COVID-19 and we were able to report in the literature 2 of the first 3 cases of SARS-CoV-2 driven pneumonia in lung transplant recipients. At this stage, our group has developed a specific research interest in this area and we are contributing to a multicenter research initiative aimed at in increasing the insight into the role of autoimmune responses on the outcome of transplant recipients.
Collaborators: Fiorella Calabrese, Federico Rea, Anna Maria Cattelan, Daniele Lilleri, Padua University Hospital and Hospital of Pavia
Marta Vadori, PhD, PostDoctoral Researcher
Annalisa Alati, Research Fellow
Lanza Edi, Project Manager
Cozzi E, Faccioli E , Marinello S , Loy M, Congedi S , Calabrese F, Romagnoli M , Cattelan AM , Rea F.COVID-19 pneumonia in lung transplant recipients: report of two cases. Am J Transplant. 2020; 20; 2933-2937.
Aron Badin R, Bugi A, Williams S, Vadori M , Michael M, Jan C , Nassi A, Lecourtois S , Blancher A , Cozzi E, Hantraye P , Perrier AL. MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates. Nat Commun. 2019; 10:4357.
Cozzi E, Calabrese F, Schiavon M, Feltracco P, Seveso M, Carollo C, Loy M, Cardillo M, Rea F. Immediate and Catastrophic Antibody-Mediated Rejection in a Lung Transplant Recipient With Anti-Angiotensin II Receptor Type 1 and Anti-Endothelin-1 Receptor Type A Antibodies. Am J Transplant 2017;17:557-564.
Aron Badin R, Vadori M, Vanhove B, Nerriere-Daguin V, Naveilhan P, Neveu I, Jan C, Lévèque X, Venturi E, Mermillod P, Van Camp N, Dollé F, Guillermier M, Denaro L, Manara R, Citton V, Simioni P, Zampieri P, D'avella D, Rubello D, Fante F, Boldrin M, De Benedictis GM, Cavicchioli L, Sgarabotto D, Plebani M, Stefani AL, Brachet P, Blancho G, Soulillou JP, Hantraye P, Cozzi E. Cell therapy for Parkinson's disease: A translational approach to assess the role of local and systemic immunosuppression. Am J Transplant 2016;16:2016-29.
O’Leary JG, Samaniego M, Barrio MC, Potena L, Zeevi A, Djamali A, Cozzi E. The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients. Transplantation 2016;100:39-53.
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