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Transplant antibody desensitization

Ji Eun Park, Chi Young Kim, Moo Suk Park, Joo Han Song, Young Sam Kim, Jin Gu Lee, Hyo Chae Paik, Song Yee Kim
BACKGROUND: Previous studies have suggested that antibodies against human leukocyte antigen (HLA) are associated with worse outcomes in lung transplantation. However, little is known about the factors associated with outcomes following lung transplantation in Asia. Accordingly, we investigated the prevalence of anti-HLA antibodies in recipients before transplantation and assessed their impact on outcomes in Korea. METHODS: A single-center retrospective study was conducted...
March 12, 2018: BMC Pulmonary Medicine
Jignesh K Patel
No abstract text is available yet for this article.
February 17, 2018: Journal of Heart and Lung Transplantation
A L Herzog, C Kalogirou, C Wanner, K Lopau
INTRODUCTION: Data suggest an additional role of T cells in antibody-mediated rejections. In 2001 a protocol for AB0-incompatible kidney transplantation based on B-cell-depleting anti-CD20 antibody rituximab, antigen-specific blood group IgG immunoadsorption, intravenous immunoglobulins, and triple immunosuppression was introduced in Europe, which used induction therapy with the use of interleukin-2 receptor antibody (IL2-RA) basiliximab. We used thymoglobulin in AB0-incompatible patients as induction in the face of high immunologic risk...
January 2018: Transplantation Proceedings
Caner Süsal, Antonij Slavcev, Lien Pham, Martin Zeier, Christian Morath
In the present review, we discuss a possible central role of T cell help in severe forms of graft damage mediated by donor-specific HLA antibodies (DSA). Some kidney transplant recipients with pretransplant DSA show a high graft failure rate, whereas in other patients DSA do not harm the transplanted kidney and in most cases disappear shortly after transplantation. Analyzing 80 desensitized highly immunized kidney transplant recipients and another multicenter cohort of 385 patients with pretransplant HLA antibodies, we reported recently that an ongoing T-cell help from an activated immune system, as measured by an increased level of soluble CD30 in serum, might be necessary for the DSA to exert a deleterious effect...
February 6, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
Yoichi Kakuta, Shigeru Satoh, Yoshihiko Watarai, Atsushi Aikawa, Kazunari Tanabe, Hiroshi Harada, Takashi Yagisawa, Hideki Ishida, Masayoshi Okumi, Shiro Takahara
Background: High-dose IVIG (2 g/kg) alone or low-dose IVIG (100 mg/kg) in conjunction with plasma exchange is typically administered as a renal transplantation desensitization therapy. Herein, we monitored changes in T cell and B cell flow cytometry crossmatch (FCXM) to assess the effects of short-term super high-dose IVIG (4 g/kg) administration with plasmapheresis before living-donor renal transplantation. Methods: Seventeen patients, each showing positive T cell FCXM (median ratio, ≥ 1...
January 2018: Transplantation Direct
Sidharth Kumar Sethi, Shyam Bihari Bansal, Nikita Wadhwani, Aseem Tiwari, Dinesh Arora, Reetesh Sharma, Ashish Nandwani, Dinesh Kumar Yadav, Amit Kumar Mahapatra, Manish Jain, Pranaw Jha, Prasun Ghosh, Anil Bhan, Maninder Dhaliwal, Veena Raghunathan, Vijay Kher
Recent literature has endorsed favorable outcomes following ABOi kidney transplantation in pediatric population. Nevertheless, reluctance to pursue an ABOi still remains pervasive. This could be ascribed to various legitimate reasons, namely less extensive pediatric ABOi data, technical difficulties encountered during PP, cost restraints, and concerns regarding higher rates of antibody-mediated rejection, infectious complications, and post-transplant lymphoproliferative disorder as compared to adults. However, given the similar excellent outcomes of both ABOi and ABOc kidney transplantation, clinicians should consider this option sooner if a compatible donor or swap is not available...
January 30, 2018: Pediatric Transplantation
Howard D Wang, Samuel A J Fidder, Devin T Miller, Georg J Furtmüller, Ali Reza Ahmadi, Felix Nägele, Joseph Lopez, Amy Quan, Joshua Budihardjo, Denver M Lough, Burcu Akpinarli, Joanna Etra, Dalibor Vasilic, Giorgio Raimondi, W P Andrew Lee, Robert A Montgomery, Zhaoli Sun, Gerald Brandacher
BACKGROUND: Candidates for vascularized composite allotransplantation (VCA) are frequently sensitized, putting them at risk for antibody-mediated rejection (AMR). Current desensitization strategies are imperfect and require a living-donor setting. Here we investigated the impact of sensitization on and the efficacy of a desensitization protocol utilizing syngeneic hematopoietic stem cell transplantation (HSCT) to prevent AMR in VCA. METHODS: Skin transplants from Dark Agouti (DA) to Lewis rats were performed for sensitization...
January 2, 2018: Transplantation
Jean Kwun, Christopher Burghuber, Miriam Manook, Brian Ezekian, Jaeberm Park, Janghoon Yoon, John S Yi, Neal Iwakoshi, Adriana Gibby, Jung Joo Hong, Alton B Farris, Allan D Kirk, Stuart J Knechtle
The detrimental effects of donor-directed antibodies in sensitized transplant patients remain a difficult immunologic barrier to successful organ transplantation. Antibody removal is often followed by rebound. Proteasome inhibitors (PIs) deplete antibody-producing plasma cells (PCs) but have shown marginal benefit for desensitization. In an allosensitized nonhuman primate (NHP) model, we observed increased germinal center (GC) formation after PI monotherapy, suggesting a compensatory PC repopulation mediated via GC activation...
November 14, 2017: Blood Advances
M Yazawa, H Sasaki, Y Sakurai, H Kudo, R Nakazawa, T Chikaraishi, Y Shibagaki
Cytomegalovirus (CMV) is a common infectious pathogen in kidney transplant patients. Here we present a case of CMV esophagitis with antigenemia, that developed within three days of kidney transplantation, a timeline generally considered to be too early for development of a CMV infection. Intense immunosuppressive therapy for desensitization in ABO-incompatibility or in the presence of donor-specific antibody can increase the risk for significant opportunistic infection immediately after or even before transplantation...
December 26, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Douglas E Gladstone, Maria P Bettinotti
Allogenic hematopoietic stem cell recipients may have preformed antibodies directed against foreign HLA antigens. The use of partially HLA-mismatched allogeneic hematopoietic stem cell donors allows for the possibility of the presence of circulating HLA donor-specific antibodies (DSAs) in the recipient. The presence of DSAs at the time of stem cell infusion increases the risk of primary graft failure. More recently developed technology using solid phase immunoassays (SPIs) with fluorochrome-conjugated beads has greatly improved the ability to detect and classify DSAs...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
Nicoletta Mancianti, Giulio Monaci, Fabio Rollo, Paola Buracchi, Andrea Guarnieri, Marina Di Luca, Mauro Martello, Guido Garosi
Modern methods for desensitization protocol rely heavily on combined apheresis therapy and Rituximab, a chimeric (murine and human) anti-CD20 antibody used in AB0 incompatible kidney transplants. Severe infusion related reactions due to the administration of Rituximab are reported in 10% of patients. These adverse reactions may hinder the completion of the desensitization protocol. Therefore, it's useful to test alternative B cell depleting therapies. Our clinical case focuses on a 41-year-old male who developed an adverse infusion reaction following the administration of Rituximab and was given Ofatumumab as an alternative treatment...
December 5, 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
Ivica Grgic, Anil Chandraker
PURPOSE OF REVIEW: Finding the right immunosuppressive approach for the individual transplant patient is of utmost importance. In truth, a 'one size fits all' does not exist, and as patients differ, so should therapeutic suppression of the immune system be individualized. For over three decades, biologics have been a central component of transplant immunosuppression. Our growing knowledge of immunological processes combined with biotechnological advances is leading to promising new therapeutic concepts and possibilities including novel biologics...
February 2018: Current Opinion in Organ Transplantation
Lucio R Requião-Moura, Taina V de Sandes-Freitas, Gessika Marcelo-Gomes, Erika B Rangel
BACKGROUND: Despite major advances in transplant medicine, antibody-mediated rejection (AMR) continues to have severe clinical implications and adversely affect graft survival. Therefore, the search for alternative drugs to treat AMR is widely pursued. The first-in-class proteasome inhibitor bortezomib (BZ) is a selective inhibitor of the 26S proteasome, which was initially approved for the treatment of malignant plasma cell disorders. METHODS: This review encompasses how our understanding of inhibiting proteasome pathway created the basis of BZ research and important milestones accomplished in AMR treatment in the transplant setting...
November 20, 2017: Current Drug Metabolism
Bassam G Abu Jawdeh, Ervin Steve Woodle, Abbie D Leino, Paul Brailey, Simon Tremblay, Tonya Dorst, Mouhamad H Abdallah, Amit Govil, Daniel Byczkowski, Hemant Misra, Abraham Abuchowski, Rita R Alloway
The endeavor to study desensitization in kidney transplantation has not been matched by an effort to investigate strategies to prevent sensitization. In this study (NCT02437422), we investigated the safety, impact on sensitization, and pharmacokinetics of SANGUINATE (SG), a hemoglobin-based oxygen carrier, as a potential alternative to packed red blood cells (PRBC) in transplant candidates with end-stage renal disease (ESRD). Ten ESRD subjects meeting inclusion/exclusion (I/E) criteria were planned to receive three weekly infusions of SG (320 mg/kg)...
January 2018: Clinical Transplantation
Seong Hoon Kim, Eung Chang Lee, Jae Ryong Shim, Sang Jae Park
BACKGROUND & AIMS: No consensus has been reached regarding optimal treatment strategies for ABO-incompatible (ABO-I) living donor liver transplantation (LDLT). We introduce a simplified protocol using rituximab and intravenous immunoglobulin (IVIG). METHODS: Data were analysed on adult patients who underwent ABO-I LDLT of which protocol added rituximab (300 mg/m(2) ) before surgery and IVIG (0.8 g/kg) on post-operative days 1 and 4 to the conventional immunosuppressive regimen used in ABO-compatible (ABO-C) LDLT, without plasmapheresis, splenectomy or graft local infusion...
October 20, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
Deepak Shankar Ray, Sharmila Thukral
BACKGROUND Even though renal transplantation across blood groups is not uncommonly practiced nowadays, there is still hesitation regarding ABO-incompatible transplantation with very high baseline antibody titer. In this case report, the outcome of an ABO-incompatible kidney transplant recipient with a high baseline isoagglutinin titer is reported. CASE REPORT The patient was a non-diabetic, 33-year-old man with end-stage renal disease secondary to chronic glomerulonephritis. The only kidney donor available was his mother, who was blood-group incompatible...
October 6, 2017: American Journal of Case Reports
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...
December 2017: Clinical Transplantation
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)
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
Hidekazu Yamamoto, Koshi Uchida, Seiichi Kawabata, Kaori Isono, Kohei Miura, Shintaro Hayashida, Yuki Oya, Yasuhiko Sugawara, Yukihiro Inomata
BACKGROUND: Rituximab is a cornerstone in the regimens of desensitization for ABO-incompatible living donor liver transplantation (ABO-i LT) that makes this modality an acceptable option for liver transplantation. Plasmapheresis (PP) to reduce anti-ABO antibody titer and local infusion therapy (LI) were practiced as the strategies for desensitization before the application of rituximab and were reported as additional treatments. The aim of this study was to clarify the feasibility of monotherapy by rituximab without any additional desensitization treatments in ABO-i LT...
September 20, 2017: Transplantation
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