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humoral rejection treatment

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
Yongkang Wu, Nicole M van Besouw, Yunying Shi, Martin J Hoogduijn, Lanlan Wang, Carla C Baan
Antibody-mediated rejection has emerged as one of the major issues limiting the success of organ transplantation. It exerts a highly negative impact on graft function and outcome, and effective treatment is lacking. The triggers for antibody development, and the mechanisms leading to graft dysfunction and failure, are incompletely understood. The production of antibodies is dependent on instructions from various immunocytes including CD4 T-helper cells that secrete interleukin (IL)-21 and interact with antigen-specific B-cells via costimulatory molecules...
2016: Frontiers in Immunology
X Wei, X Yuan, M Sun, Z Pan, L Hu, L Wang, J He, J Hou
BACKGROUND: C1q-binding donor-specific antibody (DSA) is detrimental to transplanted kidney function. However, the factors that affect C1q binding status are unclear. METHODS: A total of 519 samples from 129 consecutive kidney transplantation patients during 8 years of dynamic follow-up were collected for HLA antibody (Ab) screening and C1q detection. RESULTS: Among the detected HLA Abs, the majority were class II, and the DQ subtypes composed the highest proportion...
July 2016: Transplantation Proceedings
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
Xinqi Wu, Anita Giobbie-Hurder, Xiaoyun Liao, Donald Lawrence, David McDermott, Jun Zhou, Scott Rodig, F Stephen Hodi
Immune recognition of tumor targets by specific cytotoxic lymphocytes is essential for the effective rejection of tumors. A phase I clinical trial of ipilimumab (an antibody that blocks CTLA-4 function) in combination with bevacizumab (an antibody that inhibits angiogenesis) in patients with metastatic melanoma found favorable clinical outcomes were associated with increased tumor endothelial activation and lymphocyte infiltration. To better understand the underlying mechanisms, we sought features and factors that changed as a function of treatment in patients...
October 2016: Cancer Immunology Research
Xiao-Rui Liu, Yu-Na Guo, Chuan-Mei Qin, Xiao-Li Qin, Fei Tao, Fei Su, Fu-Ju Tian, Yan Zhang, Yi Lin
Intrauterine infection is one of the most frequent causes of miscarriage. CpG oligodeoxynucleotide (CpG ODN) can mimic intrauterine infection. CpG ODN-induced embryo-resorption was observed consistently in the NK-cell deficient non-obese diabetic (NOD) mice but not in the wild-type (WT) mice. To elucidate the molecular mechanisms of differential pregnancy outcomes, differentially expressed genes (DEGs) in the placenta and decidua basalis was revealed by RNA-Seq with CpG ODN or control ODN treatment. Common DEGs in the WT and NOD mice were enriched in antimicrobial/antibacterial humoral responses that may be activated as a primary response to bacterial infection...
2016: International Journal of Molecular Sciences
J Rashidi-Alavijeh, A Heinold, K Willuweit, H A Baba, P A Horn, A Paul, O Witzke, G Gerken, K Herzer
BACKGROUND: Donor-specific antibodies (DSAs) are increasingly being considered a cause of complications after liver transplant (LT). However, neither monitoring of DSAs nor the appropriate therapeutic procedures for humoral graft damage are yet standardized. Here we report a case of DSA-positive humoral rejection after LT that was successfully treated with plasmapheresis and immunoglobulins. METHODS: Human leukocyte antigen (HLA)-specific DSAs were detected by Luminex bead assay...
July 2016: Zeitschrift Für Gastroenterologie
Emilie Dugast, Jean-Paul Soulillou, Yohann Foucher, Emmanuelle Papuchon, Pierrick Guerif, Chloé Paul, David Riochet, Mélanie Chesneau, Anne Cesbron, Karine Renaudin, Magali Giral, Sophie Brouard
Long-term renal transplant outcome is limited by side effects of immunosuppressive drugs, particularly CNI. We assumed that some patients selected for a "low immunological risk of rejection" could be eligible and benefit from a CNI weaning strategy. We designed a prospective, randomized, multicenter, double-blind placebo-controlled clinical study (Eudract: 2010-019574-33) to analyse the benefit-risk ratio of tacrolimus weaning on highly selected patients (>= 4 years of transplantation, normal histology, stable graft function, no anti-HLA immunization)...
July 1, 2016: American Journal of Transplantation
Christina L Avila, Jason M Zimmerer, Steven M Elzein, Thomas A Pham, Mahmoud Abdel-Rasoul, Ginny L Bumgardner
BACKGROUND: De novo alloantibodies (donor-specific antibody) contribute to antibody-mediated rejection and poor long-term graft survival. Because the development of donor-specific antibody is associated with early graft loss of cell transplants and reduced long-term survival of solid organ transplants, we hypothesized that conventional immunosuppressives, calcineurin inhibitors (CNi), and mammalian target of rapamycin inhibitors (mTORi), may not be as effective for suppression of humoral alloimmunity as for cell-mediated immunity...
September 2016: Transplantation
Heidi Reich, Eleni Tseliou, Geoffrey de Couto, David Angert, Jackelyn Valle, Yuzu Kubota, Daniel Luthringer, James Mirocha, Baiming Sun, Rachel R Smith, Linda Marbán, Eduardo Marbán
BACKGROUND: A single dose of allogeneic cardiosphere-derived cells (CDCs) improves cardiac function and reduces scarring, and increases viable myocardium in the infarcted rat and pig heart without eliciting a detrimental immune response. Clinical trials using single doses of allogeneic human CDCs are underway. It is unknown whether repeat dosing confers additional benefit or if it elicits an immune response. METHODS: Wistar-Kyoto rats underwent coronary artery ligation and intramyocardial injection of CDCs, with a second thoracotomy and repeat CDC injection 3 weeks later...
May 20, 2016: Journal of Heart and Lung Transplantation
Chen Dai, Fang-Na Lu, Ning Jin, Bo Yang, Chang Gao, Bin Zhao, Jia-Zhao Fu, Shi-Fu Hong, Han-Ting Liang, Li-Hong Chen, Zhi-Shui Chen, Jie Chen, Zhong-Quan Qi
Interleukin (IL)-33 is a novel IL-1 family member, and its administration has been associated with promotion of T helper type-2 (Th2) cell activity and cytokines, particularly IL-4 and IL-5 in vivo. Recently, IL-33 was shown to increase CD4(+)Foxp3(+) regulatory T cells (Tregs) and to suppress levels of the Th1-type cytokine IFN-γ in allogeneic heart transplantation in mice. Therefore, we hypothesized that IL-33 and leflunomide (Lef) could prolong graft survival in the concordant mouse-to-rat heart transplantation model...
August 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Balázs Nemes, Roland Fedor, Zsolt Kanyári, Lajos Lőcsey, Ferenc Juhász, Dávid Ágoston Kovács, Gergely Zádori, Ferenc Győry, Réka P Szabó, Lajos Zsom, Tamás Szabó, Lóránt Illésy, Marcell Szabó-Pap, Zsolt Kincses, László Szabó, László Damjanovich, József Balla, László Asztalos
INTRODUCTION: The first renal transplantation was completed in 1991 at the University of Debrecen. In 2013 Hungary joined Eurotransplant. AIM: The authors retrospectively compared the trends. METHOD: Comparison between Period A (from January 1, 2008 to August 31, 2013) and Period B (from September 1, 2013 to October 22, 2015). RESULTS: The proportion of living transplants rose from 3.5% to 9.1 %. During period B over 25% of utilized donors were over 60 years of age...
June 12, 2016: Orvosi Hetilap
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
Ilkay Erdogan, Birgul Varan, Atilla Sezgin, Arash Pirat, Pinar Zeyneloglu
OBJECTIVES: Humoral rejection is the B-cell-mediated production of immunoglobulin G antibody against the transplanted heart. Antibody-mediated rejection may be resistant to standard immunosuppressive therapy and is associated with high mortality and graft loss. Rituximab can be used to treat antibody-mediated rejection in heart transplant recipients. This retrospective study describes our experience with rituximab treatment in children with heart transplants. MATERIALS AND METHODS: We present 7 pediatric patients with antibody-mediated rejection who were treated with plasma exchange and rituximab therapy...
May 17, 2016: Experimental and Clinical Transplantation
Jean Kanitakis, Palmina Petruzzo, Lionel Badet, Aram Gazarian, Olivier Thaunat, Sylvie Testelin, Bernard Devauchelle, Jean-Michel Dubernard, Emmanuel Morelon
Vascularized composite tissue allografts (VCA) have become a viable option to restore severely damaged parts of the body that cannot be repaired with conventional surgical techniques. Acute rejection develops frequently in the early postgraft period both in human and experimental VCA, but the possibility of human VCA to undergo chronic rejection (CR) remained initially unknown. The experience gained over the years shows that, similar to solid organ transplants (SOT), human VCA can also develop CR. Chronic rejection is clinically mostly apparent on the skin and targets preferentially skin and deep vessels, leading, as in SOT, to graft vasculopathy and often to graft loss...
October 2016: Transplantation
Muhammad M Mohiuddin, Avneesh K Singh, Philip C Corcoran, Marvin L Thomas, Tannia Clark, Billeta G Lewis, Robert F Hoyt, Michael Eckhaus, Richard N Pierson, Aaron J Belli, Eckhard Wolf, Nikolai Klymiuk, Carol Phelps, Keith A Reimann, David Ayares, Keith A Horvath
Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and αCD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed αCD40 (2C10R4) antibody...
2016: Nature Communications
B Oh, J Yoon, A Farris, A Kirk, S Knechtle, J Kwun
Previously, we demonstrated that alemtuzumab induction with rapamycin as sole maintenance therapy is associated with an increased incidence of humoral rejection in human kidney transplant patients. To investigate the role of rapamycin in posttransplant humoral responses after T cell depletion, fully MHC mismatched hearts were transplanted into hCD52Tg mice, followed by alemtuzumab treatment with or without a short course of rapamycin. While untreated hCD52Tg recipients acutely rejected B6 hearts (n = 12), hCD52Tg recipients treated with alemtuzumab alone or in conjunction with rapamycin showed a lack of acute rejection (MST > 100)...
September 2016: American Journal of Transplantation
Arash Memarnejadian, Courtney E Meilleur, Delfina M Mazzuca, Ian D Welch, S M Mansour Haeryfar
BACKGROUND: Preexisting, donor-specific antibodies (DSAs) are culprits of hyperacute rejection. Donor-specific antibodies are also formed de novo, and their role in acute and chronic rejection is increasingly appreciated. However, it is difficult to assess damage inflicted exclusively by DSAs when alloreactive T cell and B cell responses coincide. We reasoned that allosensitization with "costimulation-deficient" cells should induce DSA synthesis but not naive cytotoxic T lymphocyte (CTL) precursors' priming via direct allorecognition...
May 2016: Transplantation
Ramsey R Hachem
PURPOSE OF REVIEW: In recent years, there has been increasing awareness and appreciation for the role of humoral immune responses in lung allograft rejection. This review summarizes our current understanding of this role and the associated challenges. RECENT FINDINGS: Recent studies have described a syndrome of acute antibody-mediated rejection with a generally poor response to therapy and a high mortality. In addition, there is significant evidence implicating donor-specific human leukocyte antigen antibodies in the development of chronic lung allograft dysfunction...
June 2016: Current Opinion in Organ Transplantation
Naoyuki Morishige, Yukiko Morita, Naoyuki Yamada, Koh-Hei Sonoda
PURPOSE: To investigate the clinical characteristics of viral endotheliitis after keratoplasty, we evaluated clinical parameters in individuals with anterior chamber inflammation after keratoplasty classified according to the absence or presence of DNA from various viruses in aqueous humor. METHODS: A total of 29 eyes of 27 subjects with anterior chamber inflammation after keratoplasty were enrolled in the study. The subjects were classified into the herpes simplex virus (HSV) group (7 patients, 8 eyes), cytomegalovirus (CMV) group (6 patients, 6 eyes), varicella zoster virus group (2 patients, 2 eyes), and nonviral group (12 patients, 13 eyes) on the basis of detection of viral DNA in aqueous humor...
May 2016: Cornea
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