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Antibody rejection

Julie Zhu, Fatema Alalkim, Trana Hussaini, Siegfried R Erb, Vladimir Marquez, Mel Krajden, Douglas Webber, Eric M Yoshida
Acute hepatitis A viral (HAV) infection is rare in the liver transplant population due to recommended pre-transplant vaccinations. We report a case of acute hepatitis A infection in a liver transplant recipient. This individual had immunity to hepatitis A with protective IgG antibodies and presented with abnormal liver biochemistry in the post-transplant in-patient setting. Hepatitis A infection was confirmed by positive HAV IgM whereas other etiologies, including acute cellular rejection, were ruled out by laboratory tests and liver biopsies...
August 14, 2018: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
Marieke van der Zwan, Marian C Clahsen-Van Groningen, Joke I Roodnat, Anne P Bouvy, Casper L Slachmuylders, Willem Weimar, Carla C Baan, Dennis A Hesselink, Marcia M L Kho
BACKGROUND T cell depleting antibody therapy with rabbit anti-thymocyte globulin (rATG) is the treatment of choice for glucocorticoid-resistant acute kidney allograft rejection (AR) and is used as first-line therapy in severe AR. Almost all studies investigating the effectiveness of rATG for this indication were conducted at the time when cyclosporine A and azathioprine were the standard of care. Here, the long-term outcome of rATG for AR in patients using the current standard immunosuppressive therapy (i.e...
August 17, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Tetsu Oura, Kiyohiko Hotta, Ivy Rosales, Abbas Dehnadi, Kent Kawai, Hang Lee, A Benedict Cosimi, Tatsuo Kawai
BACKGROUND: We recently reported anti-CD40 monoclonal antibody and rapamycin (aCD40/rapa) to be a reliable, nontoxic, immunosuppressive regimen for combined islet and kidney transplantation (CIKTx) in nonhuman primates (NHPs). In the current study, we attempted to induce allograft tolerance through the mixed chimerism approach using a conditioning regimen with aCD40 and belatacept (Bela). METHODS: Five CIKTx or kidney transplant (KTx) recipients were treated with aCD40/rapa for 4 months...
August 15, 2018: Transplantation
Jens G Brockmann, Amir Butt, Hussa F Al Hussaini, Hadeel AlMana, Khaled AlSaad, Moheeb Al-Awwami, Dieter C Broering, Tariq Ali
BACKGROUND: Histological evaluation of the pancreas graft is usually done on demand resulting in significant delays. This analysis reports on endoscopic protocol duodenal graft biopsies at regular intervals to determine feasibility, safety and monitoring benefits. METHODS: Protocol duodenal graft biopsies in 27 18 consecutive pancreas transplants (10 simultaneous pancreas kidney [SPK], 17 pancreas after kidney [PAK]) with a follow-up of a minimum of 12 months were performed at days 14, 30, 90, 180, 360, 430...
August 15, 2018: Transplantation
Paloma Talayero, Esther Ramos Boluda, Elena Gómez Massa, María José Castro Panete, Gerardo Prieto Bozano, Jorge Calvo Pulido, Estela Paz-Artal, Esther Mancebo
Rejection is one of the most important drawbacks for graft and patient survival in intestinal and multivisceral transplantation. However, there is no consensus on the diagnostic criteria for humoral rejection and the literature about the role of donor specific antibodies (DSA) on the allograft outcome and the risk factors that contribute to their development is scant with contradictory results. The present study analyzes the role of DSA exclusively in a pediatric cohort of 43 transplants. Among our patients, 11...
August 16, 2018: Liver Transplantation
Aleksandar Senev, Maarten Coemans, Evelyne Lerut, Vicky Van Sandt, Liesbeth Daniëls, Dirk Kuypers, Ben Sprangers, Marie-Paule Emonds, Maarten Naesens
In this cohort study (n=935 transplantations), we investigated the phenotype and risk of graft failure in patients with histological criteria for antibody-mediated rejection (ABMR) in the absence of circulating donor-specific anti-HLA antibodies (DSA), and compared this to patients with definite ABMR and HLA-DSA-positivity. The histological picture did not differ between HLA-DSA-positive (n=85) and HLA-DSA-negative (n=123) cases of ABMR histology, apart from increased C4d deposition in the peritubular capillaries in HLA-DSA positive cases...
August 14, 2018: American Journal of Transplantation
Inigo Martinez-Zubiaurre, Anthony J Chalmers, Turid Hellevik
The implementation of novel cancer immunotherapies in the form of immune checkpoint blockers represents a major advancement in the treatment of cancer, and has renewed enthusiasm for identifying new ways to induce antitumor immune responses in patients. Despite the proven efficacy of neutralizing antibodies that target immune checkpoints in some refractory cancers, many patients do not experience therapeutic benefit, possibly owing to a lack of antitumor immune recognition, or to the presence of dominant immunosuppressive mechanisms in the tumor microenvironment (TME)...
2018: Frontiers in Immunology
Christopher K Burghuber, Miriam Manook, Brian Ezekian, Adriana C Gibby, Frank V Leopardi, Minqing Song, Jennifer Jenks, Frances Saccoccio, Sallie Permar, Alton B Farris, Neal N Iwakoshi, Jean Kwun, Stuart J Knechtle
Previous evidence suggests that a homeostatic germinal center (GC) response may limit bortezomib desensitization therapy. We evaluated the combination of costimulation blockade with bortezomib in a sensitized non-human primate kidney transplantation model. Sensitized animals were treated with bortezomib, belatacept and anti-CD40 mAb twice weekly for a month (n=6) and compared to control animals (n=7). Desensitization therapy mediated DSA reductions approached statistical significance (p=0.07) and significantly diminished bone marrow PCs, lymph node follicular helper T cells, and memory B cell proliferation...
August 13, 2018: American Journal of Transplantation
Mareen Matz, Frederik Heinrich, Christine Lorkowski, Kaiyin Wu, Jens Klotsche, Qiang Zhang, Nils Lachmann, Pawel Durek, Klemens Budde, Mir-Farzin Mashreghi
Interstitial fibrosis/tubular atrophy (IFTA) is associated with reduced allograft survival, whereas antibody-mediated rejection (ABMR) is the major cause for renal allograft failure. To identify specific microRNAs and their regulation involved in these processes, total RNA from blood cells of 16 kidney transplanted (KTx) patients with ABMR, stable graft function (SGF) and with T-cell mediated rejection (TCMR) was isolated. MicroRNA expression was determined by high-throughput sequencing. Differentially expressed candidate microRNAs were analyzed with RT-PCR in patients with SGF (n = 53), urinary tract infection (UTI) (n = 17), borderline rejection (BL) (n = 19), TCMR (n = 40), ABMR (n = 22) and IFTA (n = 30)...
2018: PloS One
Emmanuel Morelon, Palmina Petruzzo, Jean Kanitakis
PURPOSE OF REVIEW: Vascularized composite allografts (VCA), which restore severely damaged body parts that cannot be repaired with conventional surgical techniques, often undergo acute skin rejection episodes in the early postgraft period. Although the risk of human VCA to be affected by chronic rejection was initially unknown, such cases were recently observed. RECENT FINDINGS: Chronic rejection targets preferentially the skin (dermal sclerosis, adnexal atrophy, necrosis) and vessels (graft vasculopathy) and may cause graft dysfunction, often resulting in ischemic graft loss...
August 9, 2018: Current Opinion in Organ Transplantation
Peter Ulrich, Thierry Flandre, Pascal Espie, Denise Sickert, Tina Rubic-Schneider, David A Shaw, James S Rush
CFZ533 is a pathway blocking, non-depleting anti-CD40 antibody that is in clinical development for inhibition of transplant organ rejection and therapy for autoimmune diseases. A 26-week GLP toxicity study in sexually mature Cynomolgus monkeys was conducted in order to support chronic application of CFZ533. CFZ533 was subcutaneously administered at doses up to 150 mg/kg/week and was safe and generally well tolerated. CFZ533 showed no adverse effects for cardiovascular, respiratory and neurobehavioral endpoints, and no changes were observed for blood lymphocyte and platelet counts or blood coagulation markers...
August 7, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Takayuki Yamamoto, Qi Li, Hidetaka Hara, Liaoran Wang, Hongmin Zhou, Juan Li, Devin E Eckhoff, A Joseph Tector, Edwin C Klein, Ray Lovingood, Mohamed Ezzelarab, David Ayares, Yi Wang, David K C Cooper, Hayato Iwase
BACKGROUND: In the pig-to-baboon artery patch model with no immunosuppressive therapy, a graft from an α1,3-galactosyltransferase gene-knockout (GTKO) pig elicits a significant anti-nonGal IgG response, indicating sensitization to the graft. A costimulation blockade-based regimen, e.g., anti-CD154mAb or anti-CD40mAb, prevents sensitization. However, neither of these agents is currently FDA-approved. The aim of the present study was to determine the efficacy of FDA-approved agents on the T and B cell responses...
August 6, 2018: Transplant Immunology
Rudolf Spunda, Jan Hruby, Pavel Mericka, Mikulas Mlcek, Ondrej Pecha, Kathrin Splith, Moritz Schmelzle, Felix Krenzien, Jaroslav Lindner, Ivan Matia, Miroslav Spacek
OBJECTIVES AND DESIGN: The aim of our study was to simulate in rats all aspects and techniques used in our new clinical program of cryopreserved alloarterial transplantation and investigate the influence of two immunosuppressive protocols with tacrolimus on acute rejection of these allografts. MATERIALS AND METHODS: Cryopreserved abdominal aortic grafts were transplanted between Brown-Norway and Lewis rats. Tacrolimus (0.2 mg/kg daily) was administered from day 1 to day 30 (TAC1) or from day 7 to day 30 (TAC7), respectively...
2018: PloS One
Isabel Aguilera, Elena Aguado-Dominguez, Jose Manuel Sousa, Antonio Nuñez-Roldan
Antibody-mediated rejection (AMR) in liver transplantation has long been underestimated. The concept of the liver as an organ susceptible to AMR has emerged in recent years, not only in the context of the major histocompatibility complex with the presence of HLA donor-specific antibodies, but also with antigens regarded as "minor", whose role in AMR has been demonstrated. Among them, antibodies against glutathione S-transferase T1 have been found in 100% of patients with de novo autoimmune hepatitis (dnAIH) when studied...
August 7, 2018: World Journal of Gastroenterology: WJG
Sergi Luque, Marc Lúcia, Edoardo Melilli, Carmen Lefaucheur, Marta Crespo, Alex Loupy, David Bernal, Montse Gomà, Marta Jarque, Elena Crespo, Núria Montero, Anna Manonelles, Josep M Cruzado, Salvador Gil-Vernet, Josep M Grinyó, Oriol Bestard
Antibody-mediated rejection (ABMR) is defined by specific histopathological lesions and evidence of circulating donor-specific antibodies (DSA). While DSA are not always detectable, monitoring donor-reactive memory B-cells (mBC) could recognize at-risk patients of developing ABMR. Peripheral donor-reactive mBC using a novel HLA B-cell ELISpot assay, serum DSA and numbers of different B-cell subsets were assessed in 175 consecutive kidney transplants undergoing either for-cause or 6 and 24-month surveillance biopsies for their association with main histological lesions of ABMR and impact on allograft outcome...
August 7, 2018: American Journal of Transplantation
Karthi Sreedevi, Sabarinath P Subramanian, Geetha Mandagini, Padinjaradath S Appukuttan
Two heavily O-glycosylated proteins and albumin co-purified with anti-α-galactoside (anti-Gal), the chief xenograft-rejecting antibody and anti-β-glucan (ABG) antibody isolated from human plasma by affinity chromatography on respective ligand-bearing matrices. Both antibodies and O-glycoproteins co-purified with plasma albumin eluted from albumin-specific matrix. Using components of affinity-purified antibody samples separated by electrophoresis binding of either albumin or antibody to the affinity matrix of the other or binding of O-glycoprotein to either matrix was ruled out...
August 6, 2018: Immunological Investigations
Harold C Sullivan, Christina L Dean, Robert S Liwski, Shilpee Biswas, Abigail L Goodman, Scott Krummey, Howard M Gebel, Robert A Bray
Flow cytometric crossmatches (FCXM) are routinely performed to support living-donor renal transplantation. While long a laboratory mainstay, a physical crossmatch is costly, time consuming, and frequently poses interpretative conundrums with both false-positive and false negative results. Given the increased utilization of the virtual crossmatch (vXM) in the deceased donor setting, our aim was to assess its utility in living donor evaluations.We reviewed 100 living donor FCXMs and retrospectively performed a vXM for each pair...
August 3, 2018: Human Immunology
Hui Tzu Lin-Wang, Reginaldo Cipullo, João Italo Dias França, Marco Aurelio Finger, Joao Manoel Rossi Neto, Edileide de Barros Correia, Jarbas Jackson Dinkhuysen, Mário Hiroyuki Hirata
INTRODUCTION: Vasculitis entails heterogeneous origins; it starts with an inflammatory process that leads to small vessels' necrosis, hemorrhage, ischemic lesion, and may further result in occlusion of the vascular lumen. Vasculitis' contribution to allograft rejection is still unclear. This study aims to investigate the incidence of vasculitis in the early stages of heart transplantation as well as to assess the intragraft genes' expression associated with vascular function and subsequently verify the way in which it affects the outcome of the allograft...
August 6, 2018: Clinical Transplantation
Michela Cioni, Arcangelo Nocera, Augusto Tagliamacco, Sabrina Basso, Annalisa Innocente, Iris Fontana, Alberto Magnasco, Antonella Trivelli, Catherine Klersy, Antonella Gurrado, Miriam Ramondetta, Stella Boghen, Laura Catenacci, Enrico Verrina, Giacomo Garibotto, Gian Marco Ghiggeri, Massimo Cardillo, Fabrizio Ginevri, Patrizia Comoli
Current research is focusing on identifying bioclinical parameters for risk stratification of renal allograft loss, largely due to antibody-mediated rejection (AMR). We retrospectively investigated graft outcome predictors in 24 unsensitized pediatric kidney recipients developing HLA de novo donor-specific antibodies (dnDSAs), and treated for late AMR with plasmapheresis+low-dose IVIG+Rituximab or high-dose IVIG+Rituximab. Renal function and DSA properties were assessed before and longitudinally post-treatment...
August 4, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
Sergi Luque, Marc Lúcia, Elena Crespo, Marta Jarque, Josep M Grinyó, Oriol Bestard
Emerging evidence suggests that donor-reactive memory B cells (mBC) play a key role inducing antibody-mediated rejection (ABMR) after solid organ transplantation and show a broader antigen repertoire than plasma cells thus, being potentially present even in absence of donor-specific antibodies. Therefore, the development of novel immune assays capable of quantifying circulating donor-reactive mBC in organ transplantation is highly warranted. We developed a novel HLA-specific B-cell FluoroSpot assay capable of enumerating multiple HLA-specific Antibody Secreting Cells (ASC) originated from circulating mBC after in-vitro polyclonal activation...
July 31, 2018: Journal of Immunological Methods
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