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https://www.readbyqxmd.com/read/29032062/virus-specific-t-cells-broadening-applicability
#1
REVIEW
A John Barrett, Susan Prockop, Catherine M Bollard
Virus infection still remains an appreciable cause of morbidity and mortality after Hematopoietic stem cell transplant (HSCT). While pharmacotherapy and/or antibody therapy may help to prevent or treat viral disease, these drugs are expensive, toxic and often ineffective due to primary or secondary resistance. Further, effective treatments are limited for many infections (e.g. Ad and BKV), which are increasingly detected after alternative donor transplants. These deficiencies in conventional therapeutics have increased interest in an immunotherapeutic approach to viral disorders, leading to adoptive transfer of virus-specific cytotoxic T lymphocytes (VSTs), which can rapidly reconstitute antiviral immunity post-transplant without causing GvHD...
October 11, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29027535/transplant-glomerulopathy
#2
REVIEW
Edward J Filippone, Peter A McCue, John L Farber
In the renal allograft, transplant glomerulopathy represents a morphologic lesion and not a specific diagnosis. The hallmark pathologic feature is glomerular basement membrane reduplication by light microscopy or electron microscopy in the absence of immune complex deposits. Transplant glomerulopathy results from chronic, recurring endothelial cell injury that can be mediated by HLA alloantibodies (donor-specific antibodies), various autoantibodies, cell-mediated immune injury, thrombotic microangiopathy, or chronic hepatitis C...
October 13, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29026463/t-cell-allorecognition-of-donor-glutathione-s-transferase-t1-in-plasma-cell-rich-rejection
#3
María José Martínez-Bravo, Berta Sánchez, José Manuel Sousa, María José Acevedo, Miguel Angel Gómez-Bravo, Antonio Núñez-Roldán, Isabel Aguilera
AIM: To investigate the role of glutathione S-transferase T1 donor-specific T lymphocytes in plasma cell-rich rejection of liver allografts. METHODS: The study group included 22 liver transplant patients. Among them, 18 patients were mismatched for the glutathione S-transferase T1 (GSTT1) alleles (don+/rec-), and 4 were matched (don+/rec+). Seven of the mismatched patients produced anti-GSTT1 antibodies and developed plasma cell-rich rejection (former de novo immune hepatitis)...
September 28, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/29024716/accelerated-humoral-renal-allograft-rejection-due-to-hla-c14-mediated-allosensitization-to-hla-bw6
#4
Stephen P Persaud, Brian Duffy, Donna L Phelan, Thalachallour Mohanakumar, Rowena Delos Santos, Joseph P Gaut, Chang Liu
OBJECTIVES: To investigate immunological mechanisms underlying accelerated antibody-mediated rejection (AMR) of a living-related renal allograft in a patient with no detectable antibodies to donor human leukocyte antigens (HLA) in pre-transplant sera. METHODS: Pre- and post-transplant HLA antibody specificities were determined by single-antigen bead assay, and crossmatching was performed by flow cytometry- and complement-dependent cytotoxicity-based methods. Intermediate- and high-resolution HLA typing were performed by molecular methods...
October 9, 2017: Human Immunology
https://www.readbyqxmd.com/read/28990779/designer-%C3%AE-1-6-fucosidase-mutants-enable-direct-core-fucosylation-of-intact-n-glycopeptides-and-n-glycoproteins
#5
Chao Li, Shilei Zhu, Christopher Ma, Lai-Xi Wang
Core fucosylation of N-glycoproteins plays a crucial role in modulating the biological functions of glycoproteins. Yet, the synthesis of structurally well-defined, core-fucosylated glycoproteins remains a challenging task due to the complexity in multi-step chemical synthesis or the inability of the biosynthetic α1,6-fucosyltransferase (FUT8) to directly fucosylate full-size mature N-glycans in a chemoenzymatic approach. We report in this paper the design and generation of potential α1,6-fucosynthase and fucoligase for direct core-fucosylation of intact N-glycoproteins...
October 9, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28988984/prevention-of-chronic-renal-allograft-rejection-by-as2553627-a-novel-jak-inhibitor-in-a-rat-transplantation-model
#6
Koji Nakamura, Yuka Kawato, Yoko Kaneko, Kaori Hanaoka, Kaori Kubo, Tomonori Nakanishi, Masashi Maeda, Hidehiko Fukahori, Misato Ito, Takahisa Noto, Masamichi Inami, Jun Hirose, Tatsuaki Morokata
BACKGROUND: Janus kinase (JAK) inhibitors are thought to be promising candidates to aid renal transplantation. However, the effectiveness of JAK inhibitors against features of chronic rejection, including interstitial fibrosis/tubular atrophy (IF/TA) and glomerulosclerosis, has not been elucidated. Here, we investigated the effect of AS2553627, a novel JAK inhibitor, on the development of chronic rejection in rat renal transplantation. METHODS: Lewis (LEW) to Brown Norway (BN) rat renal transplantation was performed...
October 5, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28980446/anti-c1s-monoclonal-antibody-bivv009-in-late-antibody-mediated-kidney-allograft-rejection-results-from-a-first-in-patient-phase-1-trial
#7
F Eskandary, B Jilma, J Mühlbacher, M Wahrmann, H Regele, N Kozakowski, C Firbas, S Panicker, G C Parry, J C Gilbert, P F Halloran, G A Böhmig
The classical pathway (CP) of complement may contribute to the pathogenesis of antibody-mediated rejection (ABMR). Selective CP blockade may be a promising strategy to counteract rejection. The objective of this first-in-patient phase 1b trial was to evaluate the safety/tolerability and CP-blocking potential of four weekly doses (60 mg/kg) of the anti-C1s antibody BIVV009 in complement-mediated disorders. Here we describe the results in a cohort of 10 stable kidney transplant recipients (median of 4.3 years post-transplantation) with late active ABMR and features of CP activation, such as capillary C4d or complement-fixing donor-specific antibodies (DSA)...
October 5, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28979262/cd28-blockade-ex-vivo-induces-alloantigen-specific-immune-tolerance-but-preserves-t-cell-pathogen-reactivity
#8
Barbara Dillinger, Sarah Ahmadi-Erber, Klara Soukup, Angela Halfmann, Silke Schrom, Bernard Vanhove, Peter Steinberger, Rene Geyeregger, Stephan Ladisch, Alexander Michael Dohnal
Donor T-cells contribute to reconstitution of protective immunity after allogeneic hematopoietic stem cell transplantation (HSCT) but must acquire specific tolerance against recipient alloantigens to avoid life-threatening graft-versus-host disease (GvHD). Systemic immunosuppressive drugs may abrogate severe GvHD, but this also impedes memory responses to invading pathogens. Here, we tested whether ex vivo blockade of CD28 co-stimulation can enable selective T-cell tolerization to alloantigens by facilitating CD80/86-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) signaling...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28974434/graft-immunologic-events-in-deceased-donor-kidney-transplant-recipients-with-preformed-hla-donor-specific-antibodies
#9
Xicohténcatl Ixtlapale-Carmona, Adriana Arvizu, Adrian De-Santiago, Norma González-Tableros, Mayra López, Natalia Castelán, Lluvia A Marino, Norma O Uribe-Uribe, Alan G Contreras, Mario Vilatobá, Luis E Morales-Buenrostro, Josefina Alberú
INTRODUCTION: Pretransplant donor-specific HLA alloantibodies detected with the Single Antigen Bead (SAB) assay reflect an increased risk for acute antibody-mediated rejection (AMR). We herein report the incidence of both acute AMR and acute cellular rejection (ACR) during the first year posttransplantation, in a cohort of kidney transplant recipients (KTR) of deceased donor (DD) grafts, according to their DSA status. Pretransplant DSA do not preclude DD-KT in negative CDC-XM recipients at our center...
September 30, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28970687/detection-of-t-and-b-cells-specific-complement-fixing-alloantibodies-using-flow-cytometry-a-diagnostic-approach-for-a-resource-limited-laboratory
#10
Dharmendra Jain, Pranav Dorwal, Amit Pande, Neetu Tyagi, Simmi Mehra, Vimarsh Raina
BACKGROUND AND OBJECTIVES: Various methods have been reported for the detection of antibodies in recipient sera, which can be human leukocyte antigens (HLAs) or non-HLA specific, complement- or noncomplement fixing, as well as donor T (HLA-Class-I) and/or B cell (HLA-Class-I and II) specific. These alloantibodies play a pivotal role in antibody-mediated renal transplantation rejection. Deposition of C4d in peritubular capillaries of a kidney biopsy is a marker of antibody-mediated rejection...
July 2017: Asian Journal of Transfusion Science
https://www.readbyqxmd.com/read/28970678/inra-a-new-high-frequency-antigen-in-the-indian-in023-blood-group-system
#11
Sanmukh R Joshi, Ankita Sheladiya, Kinjal V Mendapara-Dobariya
BACKGROUND: The INDIAN blood group system comprises 4 antigens sensitive to enzymes and 2-aminoethyl isothiouronium bromide (AET). AIM: The patient's antibody was investigated for its specificity to the high-frequency antigens (HFA) of this system. MATERIAL AND METHODS: Low ionic strength solution (LISS)-tube/LISS-indirect antiglobulin test (IAT) methods were used. The patient's red blood cells (RBCs) were tested with antisera to HFA. Her antibody was tested with RBCs lacking the HFA...
July 2017: Asian Journal of Transfusion Science
https://www.readbyqxmd.com/read/28968970/identification-of-a-novel-hiv-1-neutralizing-antibody-from-a-crf07_bc-infected-chinese-donor
#12
Youxiang Sun, Yuanyuan Qiao, Yuanmei Zhu, Huihui Chong, Yuxian He
The identification of human monoclonal antibodies (mAbs) able to neutralize a broad spectrum of primary HIV-1 isolates is highly important for understanding the immune response of HIV-1 infection and developing vaccines and therapeutics. In this study, we isolated a novel human mAb termed Y498 from a phage display antibody library constructed with the PBMC samples of a CRF07_BC-infected Chinese donor whose sera exhibited broadly neutralizing activity. Y498 cross-reacted with diverse Env antigens and neutralized 30% of 70 tested HIV-1 isolates...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28965920/selection-and-validation-of-antibody-clones-against-igg-and-iga-subclasses-in-switched-memory-b-cells-and-plasma-cells
#13
Elena Blanco, Martin Perez-Andres, Luzalba Sanoja-Flores, Marjolein Wentink, Ondrej Pelak, Marta Martín-Ayuso, Georgiana Grigore, Juan Torres-Cañizales, Eduardo López-Granados, Tomas Kalina, Mirjam Van der Burg, Sonia Arriba-Méndez, Santiago Santa Cruz, Noemí Puig, Jacques J M van Dongen, Alberto Orfao
The clinical value of assessing immunoglobulin (Ig)G and IgA subclasses in addition to the isotypes of soluble Igs in serum has been well established. >20years ago, the International Union of Immunological Societies and the World Health Organization performed collaborative studies in order to validate antibody (Ab) clones for the detection of IgG and IgA subclasses for a broad range of laboratory assays, but except for flow cytometry. Here we analyzed the performance of commercially available Ab clones to detect IgG and IgA subclasses in memory B-cells and plasma cells (PCs) by flow cytometry...
September 28, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28958895/young-female-donors-do-not-increase-risk-of-gvhd-or-impact-overall-outcomes-in-pediatric-hla-matched-sibling-hsct
#14
Paola Friedrich, Pilar Guerra-Garcia, Alyssa Stetson, Christine Duncan, Leslie Lehmann
Optimal donor selection is critical in hematopoietic stem-cell transplantation (HSCT). Donor/recipient sex-mismatch, donor age and female donor/donor parity are known to impact graft-versus-host disease (GVHD) and outcomes in adults. Minor histocompatibility antigens (mHCA) encoded by the human Y-chromosome (H-Y) can result in specific antibody formation in some female donors, may increase in frequency with increasing donor age and may be contributory to the increased incidence of GVHD. To better understand the role of donor age/sex and sex matching in HSCT outcomes, we conducted a retrospective study of pediatric patients receiving their first myeloablative sibling-donor HSCT (n=244) from 1998 to 2012...
September 25, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28955654/the-role-of-novel-immunotherapies-in-non-hodgkin-lymphoma
#15
Allyson Pishko, Sunita D Nasta
Immunotherapy is an evolving modality in the treatment of non-Hodgkin lymphoma. Vaccinations with patient-specific tumor-derived antigens have been developed to strengthen immune response to tumor. The success of rituximab, a monoclonal antibody for CD20 on malignant B-cells, fueled further immunotherapy research. The power of the immune system to fight hematologic malignancies is seen in allogeneic stem cell transplant, where donor T cells attack residual malignant cells in the recipient. Now, three innovative therapeutic immunotherapy classes (I) adoptive cellular therapy; (II) immune-checkpoint inhibitors; and (III) novel antibody therapies show promising results in non-Hodgkin lymphoma...
February 2017: Translational Cancer Research
https://www.readbyqxmd.com/read/28955492/prongf-p75ntr-axis-plays-a-proinflammatory-role-in-inflamed-joints-a-novel-pathogenic-mechanism-in-chronic-arthritis
#16
Gaetana Minnone, Marzia Soligo, Ivan Caiello, Giusi Prencipe, Luigi Manni, Denise Pires Marafon, Silvia Magni-Manzoni, Antonio Manzo, Fabrizio De Benedetti, Luisa Bracci-Laudiero
OBJECTIVE: To identify the role of mature nerve growth factor (mNGF), its immature form proNGF and their receptors in arthritis inflammation. METHODS: Real-time PCR, western blot and ELISA were performed to evaluate NGF, proNGF, their receptor and cytokine expression in synovial tissue and cells of patients with juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA), and controls. RESULTS: proNGF and not mNGF is the prevalent form measured in synovial fluids of patients with JIA and RA with synovial fibroblasts as a major source of proNGF in the inflamed synoviae...
2017: RMD Open
https://www.readbyqxmd.com/read/28955345/protective-cytomegalovirus-cmv-specific-t-cell-immunity-is-frequent-in-kidney-transplant-patients-without-serum-anti-cmv-antibodies
#17
Nicolle H R Litjens, Ling Huang, Burç Dedeoglu, Ruud W J Meijers, Jaap Kwekkeboom, Michiel G H Betjes
The absence of anti-cytomegalovirus (CMV) immunoglobulin G (IgG) is used to classify pretransplant patients as naïve for CMV infection (CMV(neg) patients). This study assessed whether pretransplant CMV-specific T-cell immunity exists in CMV(neg) patients and whether it protects against CMV infection after kidney transplantation. The results show that CMV-specific CD137(+)IFNγ(+)CD4(+) and CD137(+)IFNγ(+)CD8(+) memory T cells were present in 46 and 39% of CMV(neg) patients (n = 28) although at much lower frequencies compared to CMV(pos) patients (median 0...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28953652/successful-kidney-transplantation-across-a-positive-complement-dependent-cytotoxicity-crossmatch-by-using-c1q-assay-directed-bortezomib-assisted-desensitization-a-case-report
#18
Juhan Lee, Borae G Park, Hyang Sook Jeong, Youn Hee Park, Sinyoung Kim, Beom Seok Kim, Hye Jin Kim, Kyu Ha Huh, Hyeon Joo Jeong, Yu Seun Kim
RATIONALE: Human leukocyte antigen (HLA) is the major immunologic barrier in kidney transplantation (KT). Various desensitization protocols to overcome the HLA barrier have increased the opportunity for transplantation in sensitized patients. In addition, technological advances in solid-phase assays have permitted more comprehensive assessment of donor-specific antibodies. Although various desensitization therapies and immunologic techniques have been developed, the final transplantation decision is still based on the classic complement-dependent cytotoxicity (CDC) crossmatch (XM) technique...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28952921/four-way-kidney-exchange-transplant-with-desensitization-increases-access-to-living-donor-kidney-transplant-first-report-from-india
#19
Vivek B Kute, Himanshu V Patel, Pankaj R Shah, Pranjal R Modi, Veena R Shah, Govind S Kasat, Mayur V Patil, Jaydeep C Patel, Deepak P Kumar, Hargovind L Trivedi
OBJECTIVES: This study reports our experience of the first 4-way kidney exchange transplant combined with desensitization in India, which allows increased access to living-donor kidney transplant for sensitized patients. MATERIALS AND METHODS: Four-way kidney exchange transplant procedures were approved by the ethics committee of our institution and the Organ Transplantation Authorization Committee of state governments of India (as per the Transplantation of Human Organs Act of India)...
September 26, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28951258/ibrutinib-suppresses-alloantibody-responses-in-a-mouse-model-of-allosensitization
#20
Irene Kim, Gordon Wu, Ning-Ning Chai, Andrew S Klein, Stanley Jordan
BACKGROUND: Ibrutinib is a Bruton's tyrosine Kinase (BTK) antagonist that inhibits B cell receptor (BCR) signaling. Complete BTK deficiency is associated with absence of B-cells. Ibrutinb is currently approved by FDA for treatment of B-cell malignancies, including Waldenström macroglobulinaemia. We recently carried out studies to determine if ibrutinib could modify alloantibody responses. MATERIALS AND METHODS: A mouse model of allogenic sensitization using a C57BL/6 mouse as the recipient of a skin allograft from an HLA-A2 transgenic mouse was utilized to examine the effects of ibrutinib on alloantibody responses and B cell effector functions...
September 23, 2017: Transplant Immunology
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