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Antibody-mediated Rejection

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https://www.readbyqxmd.com/read/28220766/immunological-biomarkers-and-long-term-graft-survival-prospective-follow-up-of-457-kidney-transplant-recipients
#1
Michał Ciszek, Krzysztof Mucha, Bartosz Foroncewicz, Dorota Żochowska, Maciej Kosieradzki, Tadeusz Grochowiecki, Magdalena Durlik, Andrzej Górski, Leszek Pączek
INTRODUCTION    Antibodies against donor`s human leukocyte antigens (HLA) play a significant role in the pathogenesis of antibody mediated rejection, although their role during the late post-transplant period is unknown. A non-HLA polymorphic antigenic system like major histocompatibility class I chain-related antigen A (MICA) might be another target for antibody responses involved in rejection. OBJECTIVES    We conducted a 7-year prospective study to determine the effect of positivity for anti-HLA and anti-MICA antibodies on kidney graft survival...
February 15, 2017: Polskie Archiwum Medycyny Wewnętrznej
https://www.readbyqxmd.com/read/28212151/antibody-mediated-rejection-in-the-cardiac-allograft-diagnosis-treatment-and-future-considerations
#2
M Elizabeth H Hammond, Abdallah G Kfoury
PURPOSE OF REVIEW: This review summarizes the latest publications dealing with antibody-mediated rejection (AMR) and defines areas of controversy and future steps that may improve the outcome for patients with this virulent form of rejection. RECENT FINDINGS: Recent progress includes publication of standardized pathologic criteria for acute AMR by the International Society for Heart and Lung Transplantation (ISHLT) and guidelines for treatment of acute AMR by the American Heart Association, endorsed by ISHLT as well...
February 15, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/28207978/glomerular-c4d-deposits-can-mark-structural-capillary-wall-remodeling-in-thrombotic-microangiopathy-and-transplant-glomerulopathy-c4d-beyond-active-antibody-mediated-injury
#3
Adil H Gasim, Jamie S Chua, Ron Wolterbeek, John Schmitz, Eric Weimer, Harsharan K Singh, Volker Nickeleit
Peritubular capillary C4d (ptc-C4d) usually marks active antibody mediated rejection, while pseudolinear glomerular capillary C4d (GBM-C4d) is of undetermined diagnostic significance, especially when seen in isolation without concurrent ptc-C4d. We correlated GBM-C4d with structural GBM abnormalities and active antibody mediated rejection in 319 renal transplant and 35 control native kidney biopsies. In kidney transplants ptc-C4d was associated with GBM-C4d in 97% by immunofluorescence microscopy (IF) and 61% by immunohistochemistry (IHC; p<0...
February 16, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28207638/association-of-local-intrapulmonary-production-of-antibodies-specific-to-donor-major-histocompatibility-complex-class-i-with-the-progression-of-chronic-rejection-of-lung-allografts
#4
Ei Miyamoto, Hideki Motoyama, Masaaki Sato, Akihiro Aoyama, Toshi Menju, Kei Shikuma, Terumasa Sowa, Akihiko Yoshizawa, Masao Saito, Akihiro Takahagi, Satona Tanaka, Mamoru Takahashi, Keiji Ohata, Takeshi Kondo, Kyoko Hijiya, Toyofumi F Chen-Yoshikawa, Hiroshi Date
BACKGROUND: Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA. METHODS: Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28199785/assessment-of-tocilizumab-anti-il-6-receptor-monoclonal-as-a-potential-treatment-for-chronic-antibody-mediated-rejection-and-transplant-glomerulopathy-in-hla-sensitized-renal-allograft-recipients
#5
Jua Choi, Olivier Aubert, Ashley Vo, Alexandre Loupy, Mark Haas, Dechu Puliyanda, Irene Kim, Sabrina Louie, Alexis Kang, Alice Peng, Joe Kahwaji, Nancy Reinsmoen, Mieko Toyoda, Stanley C Jordan
Extending the functional integrity of renal allografts is the primary goal of transplant medicine. Development of donor-specific antibodies (DSAs) post-transplant leads to chronic active antibody-mediated rejection (cABMR) and transplant glomerulopathy (TG), resulting in the majority of graft losses in the U.S. This reduces the quality & length of life for patients and increases cost. There are no approved treatments for cABMR. Evidence suggests the pro-inflammatory cytokine interleukin 6 (IL-6) may play an important role in DSA generation and cABMR...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28191005/significance-of-anti-hla-antibodies-on-adult-and-pediatric-heart-allograft-outcomes
#6
REVIEW
Massimo Mangiola, Marilyn Marrari, Brian Feingold, Adriana Zeevi
As methods for human leukocyte antigens (HLA) antibody detection have evolved and newer solid phase assays are much more sensitive, the last 15 years has seen a renewed focus on the importance of HLA antibodies in solid organ transplant rejection. However, there is still much controversy regarding the clinical significance of antibody level as depicted by the mean fluorescence intensity of a patient's neat serum. Emerging techniques, including those that identify antibody level and function, show promise for the detection of individuals at risk of allograft rejection, determination of the effectiveness of desensitization prior to transplant, and for monitoring treatment of rejection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28187998/a-systematic-review-of-the-use-of-rituximab-for-the-treatment-of-antibody-mediated-renal-transplant-rejection
#7
REVIEW
Philip S Macklin, Peter J Morris, Simon R Knight
Rituximab is a B-lymphocyte depleting agent that is used to treat hematological malignancies and autoimmune diseases. Recently, it has gained interest as an immunomodulatory agent in renal transplantation. This systematic review evaluates the evidence for its use in the treatment of acute and chronic antibody-mediated renal transplant rejection (AAMR; CAMR). A systematic search of four databases and three trial registries was conducted. The small number and heterogeneous nature of included studies precluded meta-analysis and thus a narrative review was conducted...
January 24, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28181305/de-novo-dq-donor-specific-antibodies-are-associated-with-worse-outcomes-compared-to-non-dq-dndsa-following-heart-transplantation
#8
Robert Townsend Cole, Jonathan Gandhi, Robert A Bray, Howard M Gebel, Alanna Morris, Andrew McCue, Michael Yin, S Raja Laskar, Wendy Book, Maan Jokhadar, Andrew Smith, Duc Nguyen, J David Vega, Divya Gupta
BACKGROUND: Antibody mediated rejection (AMR) resulting from de novo donor-specific antibodies (dnDSA) leads to adverse outcomes following heart transplantation (HTx). It remains unclear what role dnDSA to specific HLA antigens play in adverse outcomes. This study compares outcomes in patients developing dnDSA to DQ antigens with those developing non-DQ dnDSA and those free from dnDSA. METHODS: Single-center, retrospective analysis of 122 consecutive HTx recipients...
February 9, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28173620/proteasome-inhibitor-carfilzomib-based-therapy-for-antibody-mediated-rejection-of-the-pulmonary-allograft-use-and-short-term-findings
#9
Christopher R Ensor, Samuel A Yousem, Marilyn Marrari, Matthew R Morrell, Massimo Mangiola, Joseph M Pilewski, Jonathan D'Cunha, Stephen R Wisniewski, Raman Venkataramanan, Adriana Zeevi, John F McDyer
We present this observational study of lung transplant recipients (LTR) treated with Carfilzomib (CFZ)-based therapy for antibody-mediated rejection (AMR) of the lung. Patients were considered responders to CFZ if C1q-fixing ability of their immunodominant (ID) DSA was suppressed after treatment. Treatment consisted of CFZ plus plasma exchange and immunoglobulins. Fourteen LTRs underwent CFZ for 20 ID DSA AMR. Ten (71.4%) of LTRs responded to CFZ. DSA IgG MFI fell from 7664 (IQR 3230-11874) to 1878 (653-7791) after therapy (p=0...
February 7, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28166393/donor-specific-antibodies-c1q-binding-improvement-in-kidney-graft-management
#10
Sylvie Ferrari-Lacraz
The diagnosis of acute antibody mediated rejection (ABMR) after kidney transplantation is based on three parameters: 1) decreased renal function, 2) histopathological signs of rejection, 3) presence of Donor Specific Antibody (DSA) [1]. Patient survival, as well as graft survival have improved since 5 to 10 years [2], thanks to several factors, including better management of patients, better immunosuppressive regimens, detection and avoidance of DSA. Although anti-HLA antibodies follow-up have improved ABMR management, its treatment remains challenging, and outcome may be worsened because of a delay in the diagnosis...
February 6, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28164137/immune-responses-to-tissue-restricted-nonmajor-histocompatibility-complex-antigens-in-allograft-rejection
#11
REVIEW
Ankit Bharat, T Mohanakumar
Chronic diseases that result in end-stage organ damage cause inflammation, which can reveal sequestered self-antigens (SAgs) in that organ and trigger autoimmunity. The thymus gland deletes self-reactive T-cells against ubiquitously expressed SAgs, while regulatory mechanisms in the periphery control immune responses to tissue-restricted SAgs. It is now established that T-cells reactive to SAgs present in certain organs (e.g., lungs, pancreas, and intestine) are incompletely eliminated, and the dysregulation of peripheral immuneregulation can generate immune responses to SAgs...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28164136/the-role-of-humoral-alloreactivity-in-liver-transplantation-lessons-learned-and-new-perspectives
#12
REVIEW
Elaine Y Cheng
More than ten years after the initial description of the humoral theory of transplantation by Dr. Paul I. Terasaki, the significance of humoral alloimmunity in liver transplantation has yet to be clearly defined. The liver allograft has an inherent tolerogenic capacity which confers its resistance to cell-mediated as well as antibody-mediated rejection. Nevertheless, the protection against alloimmunity is not complete, and antibody-mediated tissue injury can occur in the liver graft under specific circumstances...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28162932/multicenter-evaluation-of-a-national-organ-sharing-policy-for-highly-sensitized-patients-listed-for-heart-transplantation-in-canada
#13
Brian Clarke, Anique Ducharme, Nadia Giannetti, Daniel Kim, Michael McDonald, Peter Pflugfelder, Miroslaw Rajda, Mario Sénéchal, Ellie Stadnick, Mustafa Toma, Shelley Zieroth, Debra Isaac
BACKGROUND: Transplantation of sensitized recipients has been associated with increased risk of post-transplant complications. In 2010, the Canadian Cardiac Transplant Network (CCTN) created a unique status listing for highly sensitized heart transplant candidates. Status 4S listing requires calculated panel-reactive antibody (cPRA) level >80% as the sole listing criteria and enables geographic expansion of the donor pool by providing national access. In this study, we describe patient characteristics and outcomes of those transplanted as Status 4S in Canada...
January 6, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28161809/alteration-of-cardiac-deformation-in-acute-rejection-in-pediatric-heart-transplant-recipients
#14
Nitin Chanana, Charlotte S Van Dorn, Melanie D Everitt, Hsin Yi Weng, Dylan V Miller, Shaji C Menon
The objective of this study is to assess changes in cardiac deformation during acute cellular- and antibody-mediated rejection in pediatric HT recipients. Pediatric HT recipients aged ≤18 years with at least one episode of biopsy-diagnosed rejection from 2006 to 2013 were included. Left ventricular systolic S (SS) and SR (SSr) data were acquired using 2D speckle tracking on echocardiograms obtained within 12 h of right ventricular endomyocardial biopsy. A mixed effect model was used to compare cardiac deformation during CR (Grade ≥ 1R), AMR (pAMR ≥ 2), and mixed rejection (CR and AMR positive) versus no rejection (Grade 0R and pAMR 0 or 1)...
February 4, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28151807/the-impact-of-antibodies-and-virtual-crossmatching-on-intestinal-transplant-outcomes
#15
Elaine Y Cheng, Bernard J DuBray, Douglas G Farmer
PURPOSE OF REVIEW: Sensitization to human leukocyte antigens (HLAs) limits access to potential donors and contributes to inferior graft survival after transplantation. In this article, we will review the effects of HLA-specific antibodies on intestinal transplant outcomes, and discuss considerations in the monitoring and treatment of anti-HLA antibodies. RECENT FINDINGS: Only a handful of studies has investigated the effects of donor-specific anti-HLA antibodies (DSAs) on intestinal allograft outcomes...
February 1, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28151033/graft-immunocomplex-capture-fluorescence-analysis-to-detect-donor-specific-antibodies-and-hla-antigen-complexes-in-the-allograft
#16
Tsukasa Nakamura, Hidetaka Ushigome, Kiyoko Watabe, Yui Imanishi, Koji Masuda, Takehisa Matsuyama, Shumpei Harada, Katsuhiro Koshino, Taku Iida, Shuji Nobori, Norio Yoshimura
BACKGROUND: Immunocomplex capture fluorescence analysis (ICFA) is an attractive method to detect donor-specific anti-HLA antibodies (DSA) and HLA antigen complexes. Currently, antibody-mediated rejection (AMR) due to DSA is usually diagnosed by C4d deposition and serological DSA detection. Conversely, there is a discrepancy between these findings frequently. Thereupon, our graft ICFA technique may contribute to establish the diagnosis of AMR. METHODS: Graft samples were obtained by a percutaneous needle biopsy...
February 2, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28148598/gene-expression-profiling-for-the-identification-and-classification-of-antibody-mediated-heart-rejection
#17
Alexandre Loupy, Jean Paul Duong Van Huyen, Luis Hidalgo, Jeff Reeve, Maud Racapé, Olivier Aubert, Jeffery M Venner, Konrad Falmuski, Marie-Cécile Bories, Thibaut Beauscart, Romain Guillemain, Arnaud François, Sabine Pattier, Claire Toquet, Arnaud Gay, Philippe Rouvier, Shaida Varnous, Pascal Leprince, Jean-Philippe Empana, Carmen Lefaucheur, Patrick Bruneval, Xavier Jouven, Philip F Halloran
BACKGROUND: -Antibody-mediated rejection (AMR) contributes to heart allograft loss. However, an important knowledge gap remains regarding the pathophysiology of AMR and how detection of immune activity, injury degree and stage could be improved by intragraft gene expression profiling. METHODS: -We prospectively monitored 617 heart transplant recipients referred from four French transplant centers (January 1st 2006 - January 1st 2011) for AMR. We compared patients with AMR (n=55) to a matched control group of 55 patients without AMR...
February 1, 2017: Circulation
https://www.readbyqxmd.com/read/28144069/a-severe-mycoplasma-pneumoniae-pneumonia-inducing-an-acute-antibody-mediated-pulmonary-graft-rejection
#18
Sarah Démir, Julien Saison, Agathe Sénéchal, Jean-Francois Mornex
A 40-year-old cystic fibrosis woman with a history of double-lung transplantation 2 years previously was admitted for a progressive respiratory distress. Physical examination revealed fever (39°C) and diffuse bilateral lung crackles. Laboratory findings included severe hypoxemia and inflammatory syndrome. Bronchoalveolar lavage and serological test were positive for mycoplasma pneumonia. As the patient did not improve after 3 days of antibiotics and donor-specific HLA antibodies had been detected, an acute antibody-mediated graft rejection was treated with high-dose corticosteroids, plasma exchange, intravenous immunoglobulin, and rituximab...
January 2017: Lung India: Official Organ of Indian Chest Society
https://www.readbyqxmd.com/read/28135788/corticosteroid-wean-after-heart-transplantation-is-there-a-risk-for-antibody-formation
#19
Omeed Elboudwarej, Derek Phan, Jignesh K Patel, Frank Liou, Tamar Aintablian, Ashley Osborne, Zhe Yu, Nancy Reinsmoen, Jon A Kobashigawa
BACKGROUND: Corticosteroid withdrawal after heart transplantation is limited to select immune-privileged patients but it is not known whether this predisposes patients to a higher risk for sensitization. METHODS: A total of 178 heart transplant recipients had panel-reactive antibody (PRA) measurements at transplant and every 6 months and were monitored for rejection with protocol endomyocardial biopsies. Corticosteroid withdrawal was initiated at 6 months post-transplant in select patients...
January 30, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28135784/morphologic-patterns-and-treatment-of-transplant-glomerulopathy-a-retrospective-analysis
#20
Rui Abreu, Fernanda Carvalho, Helena Viana, Isabel Mesquita, Marília Possante, Inês Aires, Fernando Caeiro, Cecília Silva, Patrícia Cotovio, Aníbal Ferreira, Francisco Remédio, Fernando Nolasco
Transplant glomerulopathy is mainly due to chronic antibody-mediated rejection and actually represents a major cause of long-term allograft failure. The lack of effective treatment remains a serious problem in transplantation. A retrospective and uni-center study was performed in 48 kidney allograft recipients with transplant glomerulopathy between January 2010 and December 2015. Median time for diagnosis was 7.1 (3.6-11.8) years post-transplant. Light microscopy showed severity of transplant glomerulopathy in the majority of patients (cg1=10...
January 30, 2017: Clinical Transplantation
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