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hla antibodies transplantation

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https://www.readbyqxmd.com/read/29045076/outside-in-hla-class-i-signaling-regulates-icam-1-clustering-and-endothelial-monocyte-interactions-via-mtor-in-transplant-antibody-mediated-rejection
#1
Sahar Salehi, Rebecca A Sosa, Yi-Ping Jin, Shoichi Kageyama, Michael C Fishbein, Enrique Rozengurt, Jerzy W Kupiec-Weglinski, Elaine F Reed
Antibody-mediated rejection (AMR) resulting in transplant allograft vasculopathy (TAV) is the major obstacle for long-term survival of solid organ transplants. AMR is caused by donor-specific antibodies to HLA which contribute to TAV by initiating outside-in signaling transduction pathways that elicit monocyte recruitment to activated endothelium. Mechanistic target of rapamycin (mTOR) inhibitors can attenuate TAV; therefore, we sought to understand the mechanistic underpinnings of mTOR signaling in HLA class I Ab-mediated endothelial cell activation and monocyte recruitment...
October 17, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29042454/complement-activating-anti-hla-antibodies-in-kidney-transplantation-allograft-gene-expression-profiling-and-response-to-treatment
#2
Carmen Lefaucheur, Denis Viglietti, Luis G Hidalgo, Lloyd E Ratner, Serena M Bagnasco, Ibrahim Batal, Olivier Aubert, Babak J Orandi, Federico Oppenheimer, Oriol Bestard, Paolo Rigotti, Anna V Reisaeter, Nassim Kamar, Yvon Lebranchu, Jean-Paul Duong Van Huyen, Patrick Bruneval, Denis Glotz, Christophe Legendre, Jean-Philippe Empana, Xavier Jouven, Dorry L Segev, Robert A Montgomery, Adriana Zeevi, Philip F Halloran, Alexandre Loupy
Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers...
October 17, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29037453/establishment-of-calculated-panel-reactive-antibody-and-its-potential-benefits-in-improving-the-kidney-allocation-strategy-in-taiwan
#3
Ssu-Wen Shen, Chun-Kai Chang, Yi-Shun Gao, Pin-Jou Hsu, Shuo-Chueh Cheng, Fei-Yun Liu, Shyh-Chyi Lo
BACKGROUND/PURPOSE: Renal transplant candidates who are highly sensitized to human leukocyte antigens (HLAs) tend to wait longer to find a matched donor and have poor outcomes. Most organ-sharing programs prioritize highly sensitized patients in the allocation scoring system. The HLA sensitization status is traditionally evaluated by the panel-reactive antibody (PRA) assay. However, this assay is method dependent and does not consider the ethnic differences in HLA frequencies. A calculated PRA (cPRA), based on a population's HLA frequency and patients' unacceptable antigens (UAs), correctly estimates the percentage of donors suitable for candidates...
October 13, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/29027535/transplant-glomerulopathy
#4
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/29024716/accelerated-humoral-renal-allograft-rejection-due-to-hla-c14-mediated-allosensitization-to-hla-bw6
#5
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/28988608/routine-c4d-immunohistochemistry-in-cardiac-allografts-long-term-outcomes
#6
Aliya N Husain, Kamran M Mirza, Savitri E Fedson
BACKGROUND: In the past decade, C4d has emerged as a potential marker for antibody-mediated rejection (AMR); however, evidence on its use as a prognostic tool has been controversial. Although the International Society for Heart and Lung Transplantation guideline recommends early routine surveillance of C4d in heart transplantation, there is no consensus on its value in the pathologic assessment of AMR. Herein we present a correlation analysis of C4d immunoreactivity in endomyocardial biopsies with clinical cardiac dysfunction, cellular rejection, human leukocyte antigen (HLA) status, cardiac allograft vasculopathy (CAV) and death...
September 14, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28974434/graft-immunologic-events-in-deceased-donor-kidney-transplant-recipients-with-preformed-hla-donor-specific-antibodies
#7
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
#8
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/28960455/non-traditional-sites-for-vascular-anastomoses-to-enable-kidney-transplantation-in-patients-with-major-systemic-venous-thromboses
#9
Bonnie E Lonze, Nabil N Dagher, Nada Alachkar, Annette M Jackson, Robert A Montgomery
Successful renal transplantation requires low-pressure venous drainage to permit adequate outflow from the allograft. We report here a series of three patients in whom the inferior vena cava as well as bilateral iliac veins were thrombosed, making it necessary to explore less traditional vessels for venous drainage of the renal allograft. We utilized the splanchnic vasculature in two cases, and the native left renal vein in another. The resulting atypical intra-abdominal locations of these allografts also presented difficulties for arterial anastomoses and for urinary drainage...
September 28, 2017: Clinical Transplantation
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
#10
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/28953652/successful-kidney-transplantation-across-a-positive-complement-dependent-cytotoxicity-crossmatch-by-using-c1q-assay-directed-bortezomib-assisted-desensitization-a-case-report
#11
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/28951258/ibrutinib-suppresses-alloantibody-responses-in-a-mouse-model-of-allosensitization
#12
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
https://www.readbyqxmd.com/read/28949089/treatment-of-chronic-antibody-mediated-rejection-with-intravenous-immunoglobulins-and-rituximab-a-multicenter-prospective-randomized-double-blind-clinical-trial
#13
Francesc Moreso, Marta Crespo, Juan C Ruiz, Armando Torres, Alex Gutierrez-Dalmau, Antonio Osuna, Manel Perelló, Julio Pascual, Irina B Torres, Dolores Redondo-Pachón, Emilio Rodrigo, Marcos Lopez-Hoyos, Daniel Seron
There are no approved treatments for chronic antibody mediated rejection (ABMR). We conducted a multicenter, prospective, randomized, placebo-controlled, double blind clinical trial to evaluate efficacy and safety of intravenous immunoglobulins (IVIG) combined with rituximab (RTX) (EudraCT 2010-023746-67). Patients with transplant glomerulopathy and anti-HLA donor-specific antibodies (DSA) were eligible. Patients with estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m(2) and/or severe interstitial fibrosis/tubular atrophy were excluded...
September 26, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28947279/kidney-allocation-based-on-proven-acceptable-antigens-results-in-superior-graft-survival-in-highly-sensitized-patients
#14
Sebastiaan Heidt, Geert W Haasnoot, Jon J van Rood, Marian D Witvliet, Frans H J Claas
Highly sensitized renal transplant candidates accumulate on transplant waiting lists since they produce antibodies to many HLA antigens, which in this way become unacceptable. Organ allocation to these patients is usually based on avoiding transplantation of organs bearing these unacceptable antigens. In contrast, allocation through the Eurotransplant Acceptable Mismatch (AM) program is based on extension of the patient's own HLA type with so-called acceptable HLA antigens to which strictly no antibodies are formed, as shown by extensive laboratory testing...
September 22, 2017: Kidney International
https://www.readbyqxmd.com/read/28942035/putative-role-of-kir3dl1-3ds1-alleles-and-hla-bw4-ligands-with-end-stage-renal-disease-and-long-term-renal-allograft-survival
#15
Swayam Prakash, Aditya Narayan Sarangi, Shahnawaz Alam, Avinash Sonawane, Raj Kumar Sharma, Suraksha Agrawal
BACKGROUND: Killer immunoglobulin receptors (KIR) are highly polymorphic in nature. KIR3DL1/3DS1 genes are known to affect HLA-B antigen binding affinity causing natural killer (NK) cell inhibition, which results into successful renal transplantation. In this study we have examined whether alleles of KIR3DL1/3DS1 play any role in changing the binding affinity with HLA-Bw4 antigen and if so then how are they associated with long term renal allograft survival. We have also evaluated plausible association of KIR3DL1 with HLA-A23/A24/A32 with renal pathophysiology...
December 30, 2017: Gene
https://www.readbyqxmd.com/read/28940521/the-role-of-complement-fixing-donor-specific-antibodies-identified-by-a-c1q-assay-after-heart-transplantation
#16
M Farrero Torres, M J Pando, C Luo, H Luikart, H Valantine, K Khush
BACKGROUND: The development of donor-specific antibodies (DSA) to human leukocyte antigens (HLA) has been associated with acute rejection and allograft failure after heart transplantation. Not all DSA, however, can fix complement. METHODS: To determine the association between complement-fixing DSA and heart transplant outcomes, we retrospectively analyzed results obtained using the C1q solid-phase assay that specifically detects complement-fixing DSA in parallel with the standard IgG assay in 121 adult heart transplant recipients...
September 22, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28939451/hla-haploidentical-stem-cell-transplant-with-pretransplant-immunosuppression-for-patients-with-sickle-cell-disease
#17
Anna B Pawlowska, Jerry C Cheng, Nicole A Karras, Weili Sun, Leo D Wang, Alison D Bell, Lisa Gutierrez, Joseph Rosenthal
Allogeneic stem cell transplantation (HCT) is curative in patients with severe sickle cell disease (SCD), but a significant number of patients lack an HLA-identical sibling or matched unrelated donor. Mismatched related (haploidentical) HCT with post-transplant cyclophosphamide (PTCY) allows expansion of the donor pool but is complicated by high rates of graft failure. In this report we describe a favorable haploidentical HCT approach in a limited cohort of SCD patients with significant comorbidities. To reduce the risk of graft failure we administered the conditioning regimen of rabbit antithymocyte globulin, busulfan, and fludarabine preceded with 2 courses of pretransplant immunosuppressive therapy (PTIS) with fludarabine and dexamethasone...
September 20, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28933341/c4d-expressing-glomerulopathy-and-proteinuria-post-transplantation-of-a-%C3%A2-too-big-for-size-mismatched-kidney-allograft-an-unusual-case-with-good-outcome%C3%A2
#18
Francois Gougeon, Alexei V Mikhailov, Keisha Gibson, Tomasz Kozlowski, Harsharan K Singh, Volker Nickeleit
A 5-year-old severely growth-retarded child with tubulointerstitial, oliguric end-stage renal disease received an adult-size kidney transplant. Three years post grafting under standard triple immunosuppression (mycophenolate mofetil, tacrolimus, and prednisone) de novo nephrotic range proteinuria without the nephrotic syndrome developed. Graft function was normal (serum creatinine: 0.2 - 0.3 mg/dL), there were no donor-specific HLA antibodies (DSA), and the urine sediment was inactive. Two biopsies collected 3 and 4 years post-transplantation showed severe glomerular capillary wall remodeling and associated pseudolinear C4d staining as morphologic correlates for the proteinuria...
September 21, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28930983/personalized-peptide-arrays-for-detection-of-hla-alloantibodies-in-organ-transplantation
#19
Pan Liu, Tomokazu Souma, Andrew Zu-Sern Wei, Xueying Xie, Xunrong Luo, Jing Jin
In organ transplantation, the function and longevity of the graft critically rely on the success of controlling immunological rejection reactivity against human leukocyte antigens (HLA). Histocompatibility guidelines are based on laboratory tests of anti-HLA immunity, which presents either as pre-existing or de novo generated HLA antibodies that constitute a major transplantation barrier. Current tests are built on a single-antigen beads (SAB) platform using a fixed set of ~100 preselected recombinant HLA antigens to probe transplant sera...
September 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28929636/risk-factors-for-the-development-of-antibody-mediated-rejection-in-highly-sensitized-pediatric-kidney-transplant-recipients
#20
Irene K Kim, Jua Choi, Ashley Vo, Alexis Kang, Justin Steggerda, Sabrina Louie, Mark Haas, James Mirocha, J Louis Cohen, Helen Pizzo, Elaine S Kamil, Stanley C Jordan, Dechu Puliyanda
ABMR remains a significant concern for early graft loss, especially for those who are HS against HLA antigens. We sought to determine the risk factors leading to ABMR in HS pediatric kidney transplant recipients. From January 2009 to December 2015, 16 HS pediatric kidney transplant patients at our center (age range 2-21) were retrospectively reviewed for outcomes and risk factors for ABMR. All HS patients received desensitization with high-dose IVIG/rituximab prior to transplant. Two groups were examined: ABMR(+) (n = 7) and ABMR(-) (n = 9)...
September 19, 2017: Pediatric Transplantation
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