Dr. Emmanuel Zorn
Dr. Zorn’s laboratory investigates host-graft interactions following solid organ transplantation in humans with a primary focus on B cells and antibodies in mechanisms of rejection of heart and kidney transplants. Specific avenues of research:
Role of B cells infiltrating heart transplants during cardiac allografts vasculopathy
B cell infiltrates are often observed in solid organ grafts during chronic and acute rejection, yet their function is still unclear. Our studies use cardiac allografts explanted because of rejection to isolate infiltrating B cells and determine their contribution to the rejection mechanism.
Mechanisms of chronic antibody mediated rejection of kidney allografts
Chronic humoral rejection (CHR) is one of the leading causes of late graft loss. The etiology of CHR is currently unknown. Our multicenter study uses samples collected from kidney transplant recipients at our institution as well as at collaborating centers in the USA and Europe to identify immune markers associated with CHR and piece together the causal chain leading to this complication.
Role of Natural Antibodies in host responses to solid organ grafts
Natural antibodies are broadly reactive serum immunoglobulins implicated in apoptotic cell clearance. Their contribution to inflammatory reactions associated with graft tissue destruction has not been examined. In our studies we investigate the function of these natural antibodies in acute and chronic rejection as well as in mechanisms of ischemia reperfusion injury.
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Zorn E, Miklos DB, Floyd B, Mattes-Ritz A, Guo L, Soiffer RJ, Antin JH, Ritz J. Minor Histocompatibility Antigen DBY Elicits a Coordinated B and T Cell Response After Allogeneic Stem Cell Transplantation. J Exp Med. 2004; 199:1133-1142.
Zorn E, Kim HT, Lee SJ, Floyd BH, Litsa D, Arumugarajah S, Bellucci R, Alyea EP, Antin JH, Soiffer RJ and Ritz J. Reduced frequencies of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic Graft-versus-Host-Disease. Blood. 2005; 106: 2903-2911.
Zorn E, Nelson EA, Mohseni M, Porcheray F, Kim H, Litsa D, Bellucci R, Raderschall E, Canning C, Soiffer RJ, Ritz J. IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT dependent mechanism and induces the expansion of these cells in vivo. Blood. 2006; 108:1571-9.
Zorn E, Mohseni M, Kim, H, Porcheray F, Lynch A, Bellucci R, Canning C, Alyea EP, Soiffer RJ and Ritz J. Combined CD4+ donor lymphocyte infusion and low-dose recombinant IL-2 expand FOXP3+ regulatory T cells following allogeneic hematopoietic stem cell transplantation. Biol Bone and Marrow Transplant. 2009; 15:382-8.
Porcheray F, Wong W, Saidman SL, DeVito J, Girouard TC, Chittenden M, Shaffer J, Tolkoff-Rubin N, Bimalangshu DR, Spitzer TR, Colvin RB, Cosimi AB, Kawai T, Sachs DH, Sykes M, and Zorn E. B cell immunity in the context of T cell tolerance after combined kidney and bone marrow transplantation in humans. American J. Transplant. 2009; 9:2126-35.
Porcheray F, DeVito J, Yeap BY, Xue L, Dargon I, Paine R, Girouard TC, Saidman SL, Colvin RB, Wong W and Zorn E. Chronic humoral rejection of human kidney allografts associates with broad autoantibody responses. Transplantation. 2010; 89:1239-46.
Wong W, DeVito J, Nguyen H, Sarracino D, Porcheray F, Dargon I, Pelle PD, Collins AB, Tolkoff-Rubin N, Smith RN, Colvin R and Zorn E. Chronic humoral rejection of human kidney allografts is associated with MMP-2 accumulation in podocytes and its release in the urine. American J. Transplant. 2010; 10:2463-71.
Porcheray F, Miklos D, Floyd BH, Sarantopoulos S, Bellucci R, Soiffer RJ, Antin JH, Alyea EP, Ritz J and Zorn E. Combined CD4 T cell and antibody response to human histocompatibility antigen DBY after allogeneic stem cell transplantation. Transplantation. 2011. 92:359-65.
Porcheray F, DeVito J, Helou Y, Dargon I, Fraser JW, Nobecourt P, Ferdman J, Germana S, Girouard TC, Kawai T, Saidman SL, Wong W, Colvin RB, Leguern C, and Zorn E. Expansion of polyreactive B cells cross-reactive to HLA and self in the blood of a patient with kidney graft rejection. American J. Transplant. 2012; 12: 2088-97
Porcheray, F, Fraser JW, Gao B, McColl A, DeVito J, Dargon I, Helu Y, Wong W, Girouard TC, Saidman SL, Colvin RB, Palmisano A, Maggiore U, Vaglio A, Smith RN and Zorn E. Polyreactive Antibodies Developing Amidst Humoral Rejection of Human Kidney Grafts Bind Apoptotic Cells and Activate Complement. American J. Transplant. 2013. 13:2590-600.
Ferdman J., Porcheray F., Gao B., Moore C., DeVito J., Dougherty S., Thomas M.V., Farkash., Elias N., Kawai T., Malek S.K., Tullius S.G., Wong W. and Zorn E. Expansion and somatic hypermutation of B cell clones in rejected human kidney grafts. Transplantation. 2014; In press.
Gao B., Moore C, Porcheray F., Rong C., Abidoglu A., DeVito J., Paine R., Girouard T.C., Saidman S.L., Schoenfeld D., Levin B., Wong W., Elias N., Schuetz C., Rosales I.A., Fu Y and Zorn E. Pre-Transplant IgG Reactivity to Apoptotic Cells Correlates with Late kidney Allograft Loss. American J. Transplant. 2014; In press.