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cellular and humoral rejection in kidney transplant

Isabella Guzzo, Federica Morolli, Francesca Diomedi Camassei, Antonina Piazza, Elvira Poggi, Luca Dello Strologo
BACKGROUND: Several cases of severe antibody-mediated rejection (AMR) secondary to antibodies against the angiotensin II type 1 receptor (AT1R-Ab) have been described with variable outcome. CASE-DIAGNOSIS/TREATMENT: We report the case of a 13-year-old boy whose first kidney transplant failed due to steroid-resistant acute cellular rejection, with the subsequent development of sensitization. He received a second kidney transplant which was complicated by early humoral rejection, with weakly positive staining for the complement degradation product C4d...
October 17, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Luca Dello Strologo, Luisa Murer, Isabella Guzzo, Federica Morolli, Annalisa M V Pipicelli, Elisa Benetti, Germana Longo, Sara Testa, Andrea Ricci, Fabrizio Ginevri, Luciana Ghio, Massimo Cardillo, Antonina Piazza, Alessandro Nanni Costa
BACKGROUND: High levels of preformed anti-HLA antibodies dramatically diminish renal transplant outcomes. Most desensitization programmes guarantee good intermediate outcomes but quite disappointing long-term prognosis. The search for a fully compatible kidney increases time on the waiting list. METHODS: In February 2011, a nationwide hyperimmune programme (NHP) was begun in Italy: all available kidneys are primarily proposed to highly sensitized patients with a panel reactive antibody above 80%...
October 14, 2016: Nephrology, Dialysis, Transplantation
Tristan Legris, Christophe Picard, Dilyana Todorova, Luc Lyonnet, Cathy Laporte, Chloé Dumoulin, Corinne Nicolino-Brunet, Laurent Daniel, Anderson Loundou, Sophie Morange, Stanislas Bataille, Henri Vacher-Coponat, Valérie Moal, Yvon Berland, Francoise Dignat-George, Stéphane Burtey, Pascale Paul
Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation...
2016: Frontiers in Immunology
Jason M Zimmerer, Phillip H Horne, Mason G Fisher, Thomas A Pham, Keri E Lunsford, Bryce A Ringwald, Christina L Avila, Ginny L Bumgardner
BACKGROUND: The liver immune environment is tightly regulated to balance immune activation with immune tolerance. Understanding the dominant immune pathways initiated in the liver is important because the liver is a site for cell transplantation, such as for islet and hepatocyte transplantation. The purpose of this study is to examine the consequences of alloimmune stimulation when allogeneic cells are transplanted to the liver in comparison to a different immune locale, such as the kidney...
September 2016: Transplantation
Miguel González-Molina, Pedro Ruiz-Esteban, Abelardo Caballero, Dolores Burgos, Mercedes Cabello, Miriam Leon, Laura Fuentes, Domingo Hernandez
The adaptive immune response forms the basis of allograft rejection. Its weapons are direct cellular cytotoxicity, identified from the beginning of organ transplantation, and/or antibodies, limited to hyperacute rejection by preformed antibodies and not as an allogenic response. This resulted in allogenic response being thought for decades to have just a cellular origin. But the experimental studies by Gorer demonstrating tissue damage in allografts due to antibodies secreted by B lymphocytes activated against polymorphic molecules were disregarded...
July 2016: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
Alissa J Wright, John S Gill
PURPOSE OF REVIEW: Despite improvements in posttransplant care, BK virus (BKV) remains one of the most challenging posttransplant infections in kidney transplant recipients with high rates of allograft failure. In the absence of well tolerated and efficacious viral specific therapeutics, treatment is primarily focused on reduction of immunosuppression, which poses a risk of rejection and fails to lead to viral clearance in a number of patients. RECENT FINDINGS: Recent work has turned toward preventive therapies analogous to those used for other infections like cytomegalovirus...
August 2016: Current Opinion in Infectious Diseases
Veronica Santilli, Alberto Cagigi, Isabella Guzzo, Stefano Rinaldi, Nadia Mora, Federica Zotta, Antonina Piazza, Paolo Rossi, Francesco Emma, Luca Dello Strologo, Paolo Palma
BACKGROUND: In the field of kidney transplantation, identifying early signatures of humoral rejection is a key challenge. METHODS: We investigated the presence of anti-HLA antibodies and the distribution of lymphocyte subpopulations in 77 kidney-transplanted children and young adults compared to 23 healthy controls. Moreover, we tested whether the presence of anti-HLA antibodies could be related to modification in lymphocyte phenotype. Finally, we correlated the presence of anti-HLA antibodies and specific alteration of lymphocyte subsets with clinical outcomes...
June 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Rachel Z C Teo, Germaine Wong, Graeme R Russ, Wai H Lim
AIMS: Rejection of renal allografts following transplantation continues to be a major impediment to long-term graft survival. Although acute vascular rejection (AVR) is associated with a high risk of graft loss, it remains unclear whether AVR with accompanied cellular or acute humoral rejection (AHR) have dissimilar outcomes. The aim of this registry study was to examine the association between subtypes of AVR and graft loss. METHODS: Using Australia and New Zealand Dialysis and Transplant registry, primary kidney transplant recipients between 2005 and 2012 whose first rejection episode was AVR were included and categorized into AVR-none (AVR without other rejections), AVR-CG (AVR with cellular and/or glomerular rejections), and AVR-AHR (AVR with AHR)...
February 2016: Nephrology
Balázs Nemes, Zsolt Kanyári, Gergely Zádori, Lajos Zsom, Mariann Berhés, Mátyás Hamar, Krisztina Kóbor, Antal Péter
Horseshoe kidney is a fusion anomaly found in approximately one in 400-600 people. Due to vascular and ureteral variations, transplantation with a horseshoe kidney presents a technical challenge. In our case, the isthmus connected the upper poles and contained parenchyma. It consisted of three renal arteries, five veins collected to the inferior vena cava, and two ureters and pyelons. It was implanted en bloc to the left side retroperitoneally. During the early period, cellular and humoral rejection was confirmed and treated...
June 2015: Interventional Medicine & Applied Science
James I Kim, David M Rothstein, James F Markmann
PURPOSE OF REVIEW: B cells are known to play a central role in humoral immunity and to boost cellular immunity, however, in a variety of experimental models, B-cell subsets ameliorate inflammation and autoimmune disease, indicating that they can also play a regulatory role. Here, we highlight the advances in regulatory B-cell (Breg) biology of the past year with an emphasis on findings pertinent to transplantation. Several recent observations highlight the relevance to clinical transplantation...
August 2015: Current Opinion in Organ Transplantation
S Querido, D Machado, C Silva, F Nolasco, A Nunes, S Sampaio, P Cruz, C Oliveira, A Weigert
INTRODUCTION: With the introduction of combination antiretroviral therapy (cART), prognosis of human immunodeficiency virus (HIV) infection has been improved and kidney transplantation (KT) in HIV-positive patients became possible. METHODS: We reviewed the demographic, clinical, laboratory, and therapeutic data of all the HIV-infected patients who underwent KT between 2009 (first KT in Portugal in a HIV-infected patient) and May 2014. Case accrual was through all Portuguese KT centers where a KT in an HIV-infected patient was performed...
May 2015: Transplantation Proceedings
V Warvariv, S Inokuchi, C O Esquivel
The replacement of diseased or damaged organs by transplantation became a reality in 1954, when a kidney was transplanted from one monozygotic twin to another. Barring technical difficulties, a graft between genetically identical (syngeneic) individuals is readily accepted and is termed an isograft. An allograft is a transplant between allogeneic (genetically not-identical) members of a given species, whereas a xenograft crosses species lines. Allografts and xenografts provoke a strong immunological response which, unless suppressed, leads to rejection and graft loss...
October 1993: Surgical Technology International
Parmjeet Randhawa
PURPOSE OF REVIEW: Burgeoning literature on antibody-mediated rejection (ABMR) has led to a perception that T-cell-mediated rejection (TCMR) is no longer a significant problem. This premise needs to be carefully appraised. RECENT FINDINGS: A review of the literature indicates that TCMR remains an independent-risk factor for graft loss. Importantly, it can occur as a sensitizing event that triggers ABMR, and adversely affects its outcome. Moreover, T cells are regularly present in lesions used to diagnose ABMR, and these lesions can also develop in the absence of donor-specific antibodies (DSA)...
June 2015: Current Opinion in Organ Transplantation
S Shabir, J Girdlestone, D Briggs, B Kaul, H Smith, S Daga, S Chand, S Jham, C Navarrete, L Harper, S Ball, R Borrows
Recent cross-sectional studies suggest an important role for transitional B lymphocytes (CD19 + CD24hiCD38hi) in promoting transplant tolerance, and protecting from late antibody-mediated rejection (ABMR). However, prospective studies are lacking. This study enrolled 73 de novo transplant recipients, and collected serial clinical, immunological and biochemical information over 48 ± 6 months. Cell phenotyping was conducted immediately prior to transplantation, and then on five occasions during the first year posttransplantation...
May 2015: American Journal of Transplantation
Samuel J Gavzy, Peter S Heeger
INTRODUCTION: Vitamin D (VD) has immunomodulatory properties, but whether immune cell expression of the VD receptor (VDR) impacts costimulatory blockade induced cardiac allograft survival is not known. METHODS: To localize effects of VDR deficiency to hematopoietic cells and to avoid the metabolic consequences of systemic VDR deficiency, we produced bone marrow (BM)-chimeric mice by transplanting lethally irradiated C57BL/6 mice with congenic VDR or wild type BM...
July 2015: Transplantation
Kaiyin Wu, Klemens Budde, Danilo Schmidt, Hans-Helmut Neumayer, Birgit Rudolph
BACKGROUND: It is unclear if the category of acute rejection with intimal arteritis (ARV) is relevant to short- and long-term clinical outcomes and if the graft outcomes are affected by the severity of intimal arteritis. METHODS: One hundred forty-eight ARV episodes were reviewed and categorized according to the 2013 Banff criteria of AMR: T cell-mediated rejection with intimal arteritis (v) lesion (TCMRV; n = 78), total antibody-mediated rejection with v lesion (AMRV), which were further divided into suspicious AMRV (n = 37) and AMRV (n = 33)...
August 2015: Transplantation
M Paz, J Roberti, F Mos, F Cicora
Belatacept, a fusion protein that prevents stimulation of the CD28 receptor, does not have the adverse renal, cardiovascular, and metabolic adverse effects associated with calcineurin inhibitors (CNIs). We present data on 8 renal transplant patients with graft dysfunction who were switched from CNI-based immunosuppressive therapy to belatacept in response to patients' specific needs. In patients 1 through 5, the belatacept regimen comprised 5-mg/kg doses on days 1, 15, 28, 43, and 57, then every 28 days with a decrease in the CNI dose...
November 2014: Transplantation Proceedings
Jonathan-Maurice Chemouny, Caroline Suberbielle, Marion Rabant, Julien Zuber, Marie-Alexandra Alyanakian, Xavier Lebreton, Maryvonnick Carmagnat, Nathan Pinheiro, Alexandre Loupy, Jean-Paul Van Huyen, Marc-Olivier Timsit, Dominique Charron, Christophe Legendre, Dany Anglicheau
BACKGROUND: Local inflammation is a potential cause of humoral alloimmune responses in renal transplantation, and de novo donor-specific anti-human leucocyte antigen antibodies (dnDSAs) have been associated with a history of acute rejection. METHODS: We investigated the frequencies and consequences of dnDSAs after a first episode of acute T-cell-mediated rejection (index TCMR) in previously unsensitized kidney transplant recipients. RESULTS: Of the 1,054 patients who underwent kidney transplantation between September 2004 and December 2010 at our center, we identified 75 unsensitized patients with at least one TCMR...
May 2015: Transplantation
Oleh Pankewycz, Karim Soliman, Mark R Laftavi
Historically, cellular rather than humoral immunity has gathered the most attention in kidney transplantation. As the specter of cellular acute rejection and early graft loss has faded due to the availability of highly effective immunosuppressive therapy, scientific and clinical studies now focus on improving long-term graft survival. It is increasingly appreciated that alloantibodies directed against HLA and non-HLA antigens are key factors in determining graft longevity. Significant efforts are now being made to better understand the critical impact that B cells and alloantibodies make on organ allocation and graft survival...
2014: Immunological Investigations
Mohamad Almarastani, Noura Aloudah, Mohammad Hamshow, Bassem Hegab, Khaled O Alsaad
INTRODUCTION: Spontaneous renal allograft rupture (RAR) is a serious and potentially life-threatening complication of kidney transplantation. Debate on the management of RAR has focused on graft nephrectomy versus salvaging in cases where: the allograft rupture site is surgically manageable; the bleeding can be controlled; and/or leaving the renal allograft in situ does not compromise patient survival. PRESENTATION OF CASE: A 45-year-old, living-related, female, kidney allograft recipient experienced RAR on the fourth day post transplantation...
2014: International Journal of Surgery Case Reports
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