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Antibody mediated rejection

Byung Ha Chung, Jeong Ho Kim, Bum Soon Choi, Cheol Whee Park, Ji-Il Kim, In Sung Moon, Yong-Soo Kim, Yeong Jin Choi, Eun-Jee Oh, Chul Woo Yang
Background/Aims: This study investigated the clinical significance of detecting anti-human leukocyte antigen-donor specific antibody (HLA-DSA) in kidney transplant recipients (KTRs) requiring indication biopsy owing to allograft dysfunction. Methods: We analyzed the presence of HLA-DSA in 210 KTRs who took indication biopsy. We divided these cases into two groups, HLA-DSA (+) (n = 52) and HLA-DSA (-) (n = 158) group, and compared the clinical characteristics, pathological findings, and clinical outcomes of the two groups...
October 20, 2016: Korean Journal of Internal Medicine
Yi Zheng, Yicheng Yang, Shu Wu, Yongqiang Zhu, Xiaolong Tang, Xiaopeng Liu
As the second most common gynecologic malignant tumors with a high mortality rate, cervical cancer jeopardizes women's life worldwide. The low cure rate in cervical cancer patients is mainly attributed to the lack of effective therapies. One feasible novel strategy is to develop immune-based approaches such as adoptive cell immunotherapy of DCCIKs which represents a promising nontoxic antineoplastic immunotherapy preferred in clinic practice. However, the therapeutic effect is not as efficient as anticipated...
October 18, 2016: Bioengineered
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
Yihung Huang, Evan Farkash
As both T cell and antibody-mediated rejection can have a subclinical phase, protocol biopsies provide an early opportunity to intervene before the onset of clinical allograft dysfunction. Protocol biopsies are usually done after reperfusion to establish baseline, between 3 and 6 months to identify subclinical rejection, and at 6-12 months to assess chronicity and persistent inflammation that have prognostic implication. Treatment of both subclinical T cell and antibody-mediated rejection prevents progression of rejection and development of interstitial fibrosis/tubular atrophy or transplant glomerulopathy...
September 2016: Advances in Chronic Kidney Disease
Jeffrey Ma, Anita Patel, Kathryn Tinckam
This review paper discusses the impact of de novo donor-specific antibodies (DSA) to donor HLA antigens in kidney transplantation and summarizes the benefits and challenges that exist with DSA monitoring. Post-transplant DSA is associated with worse allograft outcomes and its detection may precede or coincide with clinical, biochemical, and histologic allograft dysfunction. There are no absolute features of DSA testing results that perfectly discriminate between states of disease and health. In a state of antibody-associated graft dysfunction, removal or reduction in DSA may only provide clinical benefit for some...
September 2016: Advances in Chronic Kidney Disease
Cyril Garrouste, Dany Anglicheau, Nassim Kamar, Claire Bachelier, Joseph Rivalan, Bruno Pereira, Sophie Caillard, Julien Aniort, Philippe Gatault, Martin Soubrier, Johnny Sayegh, Charlotte Colosio, Anthony Buisson, Eric Thervet, Nicolas Bouvier, Anne Elisabeth Heng
Anti-tumor necrosis factor-α (TNFα) therapy has improved the prognosis of many chronic inflammatory diseases. It appears to be well-tolerated by liver-transplant patients. However, their use and their safety in kidney-transplant patients have yet to be determined.In this retrospective study, we identified 16 adult kidney-transplant patients aged 46.5 years (34-51.8) who received anti-TNFα therapy from 7 kidney transplantation centers. The indications for this treatment included: chronic inflammatory bowel disease (n = 8), inflammatory arthritis (n = 5), AA amyloidosis (n = 1), psoriasis (n = 1), and microscopic polyangiitis (n = 1)...
October 2016: Medicine (Baltimore)
Arnaud Del Bello, Marie Danjoux, Nicolas Congy-Jolivet, Laurence Lavayssière, Laure Esposito, Fabrice Muscari, Nassim Kamar
BACKGROUND AND AIM: Acute antibody-mediated rejection (aAMR) is an unusual complication after orthotopic ABO-compatible liver transplantation. To date, the clinical and histological long-term outcomes after aAMR are not well known. METHOD: Herein, we describe 9 cases of aAMR that occurred in our liver-transplant center between 2008 and 2016, with an initial and reevaluation liver biopsy available for reexamination. RESULTS: Two patients presented with aAMR at 10...
October 14, 2016: Journal of Gastroenterology and Hepatology
Junji Uchida, Tomoaki Iwai, Kazuya Kabei, Shunji Nishide, Takeshi Yamasaki, Nobuyuki Kuwabara, Toshihide Naganuma, Norihiko Kumada, Yoshiaki Takemoto, Tatsuya Nakatanti
INTRODUCTION: We summarized our experience with ABO-incompatible living kidney transplant recipients from spousal donors receiving rituximab. PATIENTS AND METHODS: Between June 2006 and December 2014, 82 patients with end-stage renal disease underwent living donor kidney transplantation at Osaka City University Hospital, of which 23 cases were ABO-incompatible transplantation between spouses with rituximab induction. We analyzed these recipients, focusing on their immunosuppressive protocols, frequency of acute rejections, and patient/graft survivals...
October 13, 2016: Urologia Internationalis
Hanchao Gao, Chengjiang Zhao, Xi Xiang, Yong Li, Yanli Zhao, Zesong Li, Dengke Pan, Yifan Dai, Hidetaka Hara, David K C Cooper, Zhiming Cai, Lisha Mou
Gene-knockout pigs hold great promise as a solution to the shortage of organs from donor animals for xenotransplantation. Several groups have generated gene-knockout pigs via clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) and somatic cell nuclear transfer (SCNT). Herein, we adopted a simple and micromanipulator-free method, handmade cloning (HMC) instead of SCNT, to generate double gene-knockout pigs. First, we applied the CRISPR/Cas9 system to target α1,3-galactosyltransferase (GGTA1) and cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) genes simultaneously in porcine fetal fibroblast cells (PFFs), which were derived from wild-type Chinese domestic miniature Wuzhishan pigs...
October 8, 2016: Journal of Reproduction and Development
Jorge Malheiro, Sandra Tafulo, Leonídio Dias, La Salete Martins, Isabel Fonseca, Idalina Beirão, António Castro-Henriques, António Cabrita
Detrimental impact of preformed donor-specific antibodies (DSA) against human leukocyte antigens on outcomes after kidney transplantation remains controversial. We aimed to study DSA characteristics (strength and C1q-binding) that might distinguish harmful DSA from clinically irrelevant ones. We retrospectively studied 60 kidney-transplanted patients with preformed DSA detected by single antigen beads (SAB) assays (IgG and C1q kits). Patients were divided both by DSA strength (MFI < vs. ≥15000) and C1q-binding ability...
October 7, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Ulla Derhaschnig, Jim Gilbert, Ulrich Jäger, Georg Böhmig, Georg Stingl, Bernd Jilma
BACKGROUND: Innovative trial designs are sought to streamline drug development in rare diseases. Basket- and integrated protocol designs are two of these new strategies and have been applied in a handful oncologic trials. We have taken the concept outside the realm of oncology and report about a first-in-human integrated protocol design that facilitates the transition from phase Ia in healthy volunteers to phase Ib in patients with rare complement-mediated disorders driven by the classical pathway...
October 4, 2016: Orphanet Journal of Rare Diseases
Priya Verghese, Kristen Gillingham, Arthur Matas, Srinath Chinnakotla, Blanche Chavers
The association of blood transfusions with GS after pediatric KTx is unclear. We retrospectively analyzed blood transfusions post-KTx and subsequent outcomes. Between 1984 and 2013, 482 children (<18 years of age) underwent KTx at our center. Recipient demographics, outcomes and transfusion data were collected. Cox regression with post-KTx blood transfusion as a time-dependent covariate was performed to model the impact of blood transfusion on outcomes. Of the 208 (44%) that were transfused, 39% had transfusion <1 month post-KTx; 48% >12 months...
October 6, 2016: Pediatric Transplantation
Mareen Matz, Christine Lorkowski, Katharina Fabritius, Kaiyin Wu, Birgit Rudolph, Stefan Frischbutter, Susanne Brakemeier, Jens Gaedeke, Hans-H Neumayer, Mir-Farzin Mashreghi, Klemens Budde
Cellular and antibody-mediated rejection processes and also interstitial fibrosis/tubular atrophy (IFTA) lead to allograft dysfunction and loss. The search for accurate, specific and non-invasive diagnostic tools is still ongoing and essential for successful treatment of renal transplanted patients. Molecular markers in blood cells and serum may serve as diagnostic tools but studies with high patient numbers and differential groups are rare. We validated the potential value of several markers on mRNA level in blood cells and serum protein level in 166 samples from kidney transplanted patients under standard immunosuppressive therapy (steroids±mycophenolic acid±calcineurin inhibitor) with stable graft function, urinary tract infection (UTI), IFTA, antibody-mediated rejection (ABMR), and T-cell-mediated rejection (TCMR) applying RT-PCR and ELISA...
September 29, 2016: Transplant Immunology
Guo-Sheng Wu
Antibody-mediated rejection (ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation (ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibody-mediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients...
September 24, 2016: World Journal of Transplantation
Silke Rummler, Astrid Bauschke, Erik Bärthel, Heike Jütte, Katrin Maier, Patrice Ziehm, Christina Malessa, Utz Settmacher
For a long time, it was considered medical malpractice to neglect the blood group system during transplantation. Because there are far more patients waiting for organs than organs available, a variety of attempts have been made to transplant AB0-incompatible (AB0i) grafts. Improvements in AB0i graft survival rates have been achieved with immunosuppression regimens and plasma treatment procedures. Nevertheless, some grafts are rejected early after AB0i living donor liver transplantation (LDLT) due to antibody mediated rejection or later biliary complications that affect the quality of life...
September 24, 2016: World Journal of Transplantation
Sophie Caillard, Camille Becmeur, Gabriela Gautier-Vargas, Jerome Olagne, Clotilde Muller, Noelle Cognard, Peggy Perrin, Laura Braun, Francoise Heibel, Francois Lefebre, Veronique Renner, Christian Gachet, Bruno Moulin, Anne Parissiadis
Donor-specific antibodies (DSA) increase the risk of allograft rejection and graft failure. They may be present before transplant or develop de novo after transplantation. Here, we studied the evolution of preformed DSA and their impact on graft outcome in kidney transplant recipients. Using the Luminex Single Antigen assay, we analyzed the sera on the day of transplantation of 239 patients who received a kidney transplant. Thirty-seven patients (15.5%) had pre-existing DSA detected the day of transplantation...
September 28, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Amy E McAlister, Kira Geile, Carmen M Halabi, T Keefe Davis
We describe the successful treatment of a pediatric transplant patient with simultaneous intermittent hemodialysis and therapeutic plasma exchange (TPE). The patient presented with kidney graft failure. He had life threatening electrolyte disturbances and fluid overload due to antibody-mediated rejection. Therefore, he was in need of both emergent kidney replacement therapy and TPE. Both extracorporeal circuits were set up, established, and maintained safely and effectively without difficulty or alarms. Running intermittent hemodialysis and TPE simultaneously significantly reduced therapy time, allowed both needed therapies priority, and provided a superior pediatric patient experience in an acute situation...
October 2016: Hemodialysis International
Mareen Matz, Christine Lorkowski, Katharina Fabritius, Pawel Durek, Kaiyin Wu, Birgit Rudolph, Hans-H Neumayer, Mir-Farzin Mashreghi, Klemens Budde
The potential diagnostic value of circulating free miRNAs in plasma compared to miRNA expression in blood cells for rejection processes after kidney transplantation is largely unknown, but offers the potential for better and timely diagnosis of acute rejection. Free microRNA expression of specific blood cell markers was measured in 160 plasma samples from kidney transplant patients under standard immunosuppressive therapy (steroids±mycophenolic acid±calcineurin inhibitor) with stable graft function, urinary tract infection, interstitial fibrosis and tubular atrophy, antibody-mediated rejection (ABMR), Borderline (Banff3), tubulo-interstitial (Banff4-I) and vascular rejection (Banff4-II/III) applying RT-PCR...
September 20, 2016: Transplant Immunology
Sourabh Chand, David Atkinson, Clare Collins, David Briggs, Simon Ball, Adnan Sharif, Kassiani Skordilis, Bindu Vydianath, Desley Neil, Richard Borrows
BACKGROUND: Causes of "true" late kidney allograft failure remain unclear as study selection bias and limited follow-up risk incomplete representation of the spectrum. METHODS: We evaluated all unselected graft failures from 2008-2014 (n = 171; 0-36 years post-transplantation) by contemporary classification of indication biopsies "proximate" to failure, DSA assessment, clinical and biochemical data. RESULTS: The spectrum of graft failure changed markedly depending on the timing of allograft failure...
2016: PloS One
Joshua L Chan, Jon A Kobashigawa, Heidi J Reich, Danny Ramzy, Maria M Thottam, Zhe Yu, Tamar L Aintablian, Frank Liou, Jignesh K Patel, Michelle M Kittleson, Lawrence S Czer, Alfredo Trento, Fardad Esmailian
BACKGROUND: The Organ Care System, an ex-vivo heart perfusion platform, represents an alternative to the current standard of cold organ storage that sustains the donor heart in a near-physiologic state. It is unknown whether using the Organ Care System influences 2-year outcomes after heart transplantation. We reviewed our institutional experience to compare 2-year outcomes for patients randomized to the Organ Care System or standard cold storage. METHODS: Between 2011 and 2013, heart transplant candidates from a single tertiary-care medical center enrolled within the PROCEED II trial were randomized to either standard cold storage or the Organ Care System...
August 20, 2016: Journal of Heart and Lung Transplantation
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