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Hla antibody monitoring

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https://www.readbyqxmd.com/read/28729289/class-ii-eplet-mismatch-modulates-tacrolimus-trough-levels-required-to-prevent-donor-specific-antibody-development
#1
Chris Wiebe, David N Rush, Thomas E Nevins, Patricia E Birk, Tom Blydt-Hansen, Ian W Gibson, Aviva Goldberg, Julie Ho, Martin Karpinski, Denise Pochinco, Atul Sharma, Leroy Storsley, Arthur J Matas, Peter W Nickerson
Despite more than two decades of use, the optimal maintenance dose of tacrolimus for kidney transplant recipients is unknown. We hypothesized that HLA class II de novo donor-specific antibody (dnDSA) development correlates with tacrolimus trough levels and the recipient's individualized alloimmune risk determined by HLA-DR/DQ epitope mismatch. A cohort of 596 renal transplant recipients with 50,011 serial tacrolimus trough levels had HLA-DR/DQ eplet mismatch determined using HLAMatchmaker software. We analyzed the frequency of tacrolimus trough levels below a series of thresholds <6 ng/ml and the mean tacrolimus levels before dnDSA development in the context of HLA-DR/DQ eplet mismatch...
July 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28638610/looking-for-the-needle-in-the-kidney-transplantation-haystack
#2
Josep M Cruzado, Edoardo Melilli
The diagnosis of acute rejection still relies on renal allograft biopsy. In fact, histological features including C4d staining can be useful to differentiate cellular and antibody-mediated acute rejection. However, the pathogenic mechanism to define the type of rejection is usually assessed by anti-HLA donor specific antibodies (DSA) monitoring. Suspicion of acute rejection is usually based on renal function deterioration. This method has low sensitivity. Moreover, creatinine increase follows graft injury and therefore the diagnosis is performed when there is an ongoing acute rejection...
February 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28606713/rhabdomyolysis-and-coeliac-disease-a-causal-or-casual-association-a-case-report-and-review-of-literature
#3
Claudia Mandato, Alessandro Rossi, Mariano Caldore, Marta Lamba, Michele Rocco, Renata Auricchio, Pietro Vajro, Paolo Siani
BACKGROUND: Rhabdomyolysis is a rare, potentially life-threatening condition, caused by multiple disorders. The association with Coeliac Disease (CD) has been rarely reported and in these cases muscular damage was imputed to hypokalemia. Herein we describe a new case of severe rhabdomyolysis in a child subsequently diagnosed as affected by CD, and review previous reports. CASE PRESENTATION: A 3-year-old boy was referred for diarrhea, brown urine, muscular pain/weakness, and no history of muscular trauma...
June 9, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28585289/effects-of-weak-non-complement-binding-hla-antibodies-on-c1q-binding
#4
G Hönger, P Amico, M-L Arnold, B M Spriewald, S Schaub
It is unknown under what conditions and to what extent weak/non-complement (C)-binding IgG subclasses (IgG2/IgG4) can block C1q-binding triggered by C-binding IgG subclasses (IgG1/IgG3). Therefore, we investigated in vitro C1q-binding induced by IgG subclass mixtures targeting the same HLA epitope. Various mixtures of HLA class II specific monoclonal antibodies of different IgG subclasses but identical V-region were incubated with HLA DRB1*07:01 beads and monitored for C1q-binding. The lowest concentration to achieve maximum C1q-binding was measured for IgG3, followed by IgG1, while IgG2 and IgG4 did not show appreciable C1q-binding...
June 5, 2017: HLA
https://www.readbyqxmd.com/read/28571148/de-novo-focal-segmental-glomerulosclerosis-in-renal-allograft-histological-presentation-and-clinical-correlation-single-centre-experience
#5
Rashmi D Patel, Aruna V Vanikar, Lovelesh A Nigam, Kamal V Kanodia, Kamlesh S Suthar, Himanshu V Patel
INTRODUCTION: Recurrent or de novo glomerulonephritis are one of the well-known causes for renal allograft dysfunction in early and late period after renal transplantation. Focal Segmental Glomerulosclerosis (FSGS) is a devastating lesion of the renal allograft. De novo FSGS is uncommon compared to recurrent FSGS. AIM: To find out the incidence of de novo FSGS. MATERIALS AND METHODS: A retrospective evaluation of renal allograft biopsies was performed from 2007 to 2015, by light microscopy and immunohistochemistry including patient-donor demographics...
April 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28566880/immune-response-to-vaccines-in-children-with-celiac-disease
#6
EDITORIAL
Caterina Anania, Francesca Olivero, Alessandra Spagnolo, Claudio Chiesa, Lucia Pacifico
Celiac disease (CD) is an immune-mediated systemic condition evoked by ingestion of gluten and related prolamines in genetically susceptible subjects. The disease is featured by a variable combination of clinical signs, specific antibodies, HLA-DQ2 and HLA-DQ8 haplotypes, and enteropathy. Vaccination is the most potent intervention for infectious disease prevention. Several factors including age, gender, ethnicity, quality and quantity of vaccine antigen, doses, and route of administration can influence immune response to vaccination, although the main cause of variation in the responsiveness among vaccine recipients is host genetic variability...
May 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28552231/from-open-to-large-scale-randomized-cell-transplantation-trials-in-huntington-s-disease-lessons-from-the-multicentric-intracerebral-grafting-in-huntington-s-disease-trial-mig-hd-and-previous-pilot-studies
#7
Anne-Catherine Bachoud-Lévi
Fifty-one patients from open-label pilot trials have been transplanted in Huntington's disease (HD) using human fetal cells; clinical data and follow-up are available in 30 of them. These open-label studies were mostly designed for safety and feasibility. However, signs of long-term efficacy have been reported in 4 out of 30 patients, differences in tissue preparation, surgical procedure, patients characteristics, immunosuppression regimens, clinical, and imaging assessments, makes it difficult to define the optimal procedure for future trials...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28501500/it-s-about-time-the-development-and-validation-of-a-rapid-optimized-single-antigen-bead-rob-assay-protocol-for-labscreen
#8
Robert S Liwski, Anna L Greenshields, Cathi Murphey, Robert A Bray, Howard M Gebel
The LABScreen single antigen bead assay (SAB) is a method widely used for the identification and monitoring of human leukocyte antigen (HLA) antibodies in patients pre-and post-transplant. While accurate testing of patient samples is key for optimal patient care, time can also be important, especially during deceased donor workups or post-transplant assessments. Here we describe the development and validation of the Rapid Optimized SAB (ROB) protocol, a modified version of the One Lambda LABScreen SAB (OLSAB) procedure, which reduces assay time from 85 to 25min (>70% reduction) without impacting assay quality or sensitivity...
May 10, 2017: Human Immunology
https://www.readbyqxmd.com/read/28480647/increased-circulating-t-lymphocytes-expressing-hla-dr-in-kidney-transplant-recipients-with-microcirculation-inflammation
#9
Hee Yeon Jung, Yong Jin Kim, Ji Young Choi, Jang Hee Cho, Sun Hee Park, Yong Lim Kim, Hyung Kee Kim, Seung Huh, Dong Il Won, Chan Duck Kim
We consecutively enrolled 82 kidney transplant recipients (KTRs) with stable renal function and 24 KTRs who underwent indication biopsy to compare the histological grading of renal allografts with the activity of circulating T lymphocyte subsets and monocytes determined by flow cytometry, which were obtained at 2 weeks after kidney transplantation (KT) and at the time of indication biopsy, respectively. The sum of the scores of glomerulitis (g) + peritubular capillaritis (ptc), inflammation (i) + tubulitis (t), interstitial fibrosis (ci) + tubular atrophy (ct), and fibrointimal thickening (cv) + arteriolar hyaline thickening (ah) was used to assign a histological grade to the renal allograft samples...
June 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28476933/nature-and-clonality-of-the-fluoresceinated-secondary-antibody-in-luminex-multiplex-bead-assays-are-critical-factors-for-reliable-monitoring-of-serum-hla-antibody-levels-in-patients-for-donor-organ-selection-desensitization-therapy-and-assessment-of-the-risk
#10
Mepur H Ravindranath, Vadim Jucaud, Nubia Banuelos, Matthew J Everly, Junchao Cai, Anh Nguyen, Paul I Terasaki
Luminex multiplex immunoassays enable simultaneous monitoring of Abs against multiple Ags in autoimmune, inflammatory, and infectious diseases. The assays are used extensively to monitor anti-HLA Abs in transplant patients for donor organ selection, desensitization, and assessing the risk for graft rejection. To monitor IgG Abs, fluoresceinated IgG constant H chain-binding polyclonal F(ab')2 (IgHPolyFab) is used as the fluoresceinated secondary Ab (2nd-Ab), whereas IgG subclasses are monitored with Fc-specific monoclonal whole IgG (FcMonoIgG)...
May 5, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28457920/antibody-response-to-hbv-vaccination-on-dialysis-does-not-correlate-with-the-development-of-denovo-anti-hla-antibodies-after-renal-transplantation
#11
Teresa Kauke, Maximilian Link, Markus Rentsch, Manfred Stangl, Markus Guba, Joachim Andrassy, Jens Werner, Bruno Meiser, Michael Fischereder, Antje Habicht
BACKGROUND: Response to Hepatitis B virus (HBV) vaccination can be diminished in some (50-80%) but not all dialysis patients. We hypothesized, that the response to vaccination on dialysis may correlate with the development of anti-HLA antibodies after renal transplantation and might therefore be a valuable parameter to predict alloresponses. METHODS: The response to HBV vaccination on dialysis and the development of deNovo anti-HLA antibodies post-transplant was analyzed in 188 non-immunized renal transplant recipients...
June 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28448627/engineering-chimeric-human-and-mouse-major-histocompatibility-complex-mhc-class-i-tetramers-for-the-production-of-t-cell-receptor-tcr-mimic-antibodies
#12
Demin Li, Carol Bentley, Jenna Yates, Maryam Salimi, Jenny Greig, Sarah Wiblin, Tasneem Hassanali, Alison H Banham
Therapeutic monoclonal antibodies targeting cell surface or secreted antigens are among the most effective classes of novel immunotherapies. However, the majority of human proteins and established cancer biomarkers are intracellular. Peptides derived from these intracellular proteins are presented on the cell surface by major histocompatibility complex class I (MHC-I) and can be targeted by a novel class of T-cell receptor mimic (TCRm) antibodies that recognise similar epitopes to T-cell receptors. Humoural immune responses to MHC-I tetramers rarely generate TCRm antibodies and many antibodies recognise the α3 domain of MHC-I and β2 microglobulin (β2m) that are not directly involved in presenting the target peptide...
2017: PloS One
https://www.readbyqxmd.com/read/28447925/luminex-solid-phase-crossmatch-for-de-novo-donor-specific-antibodies-in-living-donor-related-transplants
#13
Sonia Mehrotra, Raj Kumar Sharma, Mahabaleshwar Mayya, Amit Gupta, Narayan Prasad, Anupma Kaul, Dharmendra Singh Bhadauria
OBJECTIVES: There are no reports of de novo donor-specific antibody monitoring by a low-cost solid-phase crossmatch assay using donor lysate after renal transplant. MATERIALS AND METHODS: We prospectively evaluated 121 complement-dependant cytotoxicity crossmatch-negative living-donor kidney transplant recipients for development of de novo donor-specific antibodies (class I and II HLA) by solid-phase crossmatch Luminex assay after transplant. RESULTS: Of 121 recipients in our study group, 26 (21...
April 27, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28403566/outcomes-and-risk-stratification-for-late-antibody-mediated-rejection-in-recipients-of-abo-incompatible-kidney-transplants-a-retrospective-study
#14
Bonnie E Lonze, Sunjae Bae, Edward S Kraus, Mary J Holechek, Karen E King, Nada Alachkar, Fizza F Naqvi, Nabil N Dagher, Adnan Sharif, Niraj M Desai, Dorry L Segev, Robert A Montgomery
The required intensity of monitoring for antibody-mediated rejection (AMR) after of ABO-incompatible (ABOi) kidney transplantation is not clearly formulized. We retrospectively evaluated a single-center cohort of 115 ABO-incompatible (ABOi) kidney transplant recipients, of which 32% were also HLA incompatible (ABOi/HLAi) with their donors. We used an adjusted negative binomial model to evaluate risk factors for late AMR. Using this model, we risk-stratified patients into high- and low-risk groups for the development of late AMR; 26% of patients had at least one AMR episode; 49% of AMR episodes occurred within 30-days after transplant and were considered early AMR...
April 12, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28372986/assessing-the-potential-of-angiotensin-ii-type-1-receptor-and-donor-specific-anti-endothelial-cell-antibodies-to-predict-long-term-kidney-graft-outcome
#15
David F Pinelli, John J Friedewald, Kelley M K Haarberg, Shree L Radhakrishnan, Jennifer R Zitzner, Wendy E Hanshew, Anat R Tambur
Endothelial cell antigens have been reported as potential targets for antibodies in the context of organ transplantation, leading to increased risk for graft failure. Serum samples from 142 consecutive living donor kidney recipients were tested for the presence of antibodies to angiotensin II - type 1 receptor (AT1R), donor endothelial cells, and donor HLA. Graft survival was monitored for five years post-transplant, and secondary outcomes, including biopsy-proven rejection, proteinuria, biopsy-proven vasculopathy, and renal function based on serum creatinine were also assessed for the first two to three years...
March 31, 2017: Human Immunology
https://www.readbyqxmd.com/read/28364254/characterisation-of-rapid-progressors-to-type-1-diabetes-among-children-with-hla-conferred-disease-susceptibility
#16
Petra M Pöllänen, Johanna Lempainen, Antti-Pekka Laine, Jorma Toppari, Riitta Veijola, Paula Vähäsalo, Jorma Ilonen, Heli Siljander, Mikael Knip
AIMS/HYPOTHESIS: In this study, we aimed to characterise rapid progressors to type 1 diabetes among children recruited from the general population, on the basis of HLA-conferred disease susceptibility. METHODS: We monitored 7410 HLA-predisposed children participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study for the development of beta cell autoimmunity and type 1 diabetes from birth over a median follow-up time of 16.2 years (range 0...
March 31, 2017: Diabetologia
https://www.readbyqxmd.com/read/28348361/the-impact-of-donor-specific-anti-human-leukocyte-antigen-hla-antibody-rebound-on-the-risk-of-antibody-mediated-rejection-in-sensitized-kidney-transplant-recipients
#17
Kyo Won Lee, Jae Berm Park, Chan Woo Cho, Nuri Lee, Heejin Yoo, Kyunga Kim, Hyojun Park, Eun Suk Kang, Wooseong Huh, Sungjoo Kim
BACKGROUND Donor-specific anti-HLA antibody (DSA) detected on Luminex-based single antigen assay (LSA) has become the subject of desensitization based upon the results of previous studies. We retrospectively investigated the impact of preoperative DSA on the incidence of antibody mediated rejection (AMR) in patients desensitized using a protocol based on rituximab and rabbit antithymocyte globulin (rATG). MATERIAL AND METHODS Nine patients (Group 1, 9/327, 2.8%) were complement dependent cytotoxicity crossmatch (CDC-XM) positive and underwent desensitization with rituximab (375 mg/m²), intravenous immunoglobulin (IVIG; 400 mg/kg), plasmapheresis, and rATG...
March 28, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28339671/characteristics-of-donor-specific-anti-hla-antibodies-and-outcome-in-renal-transplant-patients-treated-with-a-standardized-induction-regimen
#18
Daniel Zecher, Christian Bach, Christoph Staudner, Carsten A Böger, Tobias Bergler, Bernhard Banas, Bernd M Spriewald
Background.: Pre-transplant donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have been associated with antibody-mediated rejection (AMR) and early kidney allograft loss. Uncertainties remain regarding the general applicability of these findings and the optimal induction therapy in DSA-positive patients. Methods.: Pre-transplant sera from 174 patients receiving a crossmatch-negative kidney transplant were retrospectively analysed for DSA using Luminex technology...
April 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339124/gliadin-reactive-t-cells-in-italian-children-from-preventcd-cohort-at-high-risk-for-celiac-disease
#19
Alessandra Camarca, Renata Auricchio, Stefania Picascia, Olga Fierro, Mariantonia Maglio, Erasmo Miele, Basilio Malamisura, Luigi Greco, Riccardo Troncone, Carmen Gianfrani
BACKGROUND: Newborns at high risk for celiac disease (CD) were recruited in Italy in the context of the PreventCD Study and closely monitored for CD, from 4 months up to a mean age of 8 years at follow-up. The aim of our study was to investigate intestinal T cell reactivity to gliadin at the first clinical and/or serological signs of CD. METHODS: Gliadin-reactive T cell lines were generated from intestinal biopsies of 19 HLA-DQ2 or HLA-DQ8 positive children. At biopsy, 11 children had a diagnosis of acute CD, two of potential CD, and six were non-celiac controls...
March 24, 2017: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/28336908/early-chimerism-after-liver-transplantation-reflects-the-clinical-course-of-recurrent-hepatitis-c
#20
Masashi Utsumi, Akinobu Takaki, Yuzo Umeda, Kazuko Koike, Stephanie C Napier, Nobukazu Watanabe, Susumu Shinoura, Ryuichi Yoshida, Daisuke Nobuoka, Tetsuya Yasunaka, Takahiro Oto, Motoo Araki, Kazuhide Yamamoto, Toshiyoshi Fujiwara, Takahito Yagi
BACKGROUND Human leukocyte antigen (HLA) mismatch is a characteristic feature of post-orthotopic liver transplantation (OLT) hepatitis C. To investigate the importance of donor HLA-restricted immune cells in post-OLT hepatitis C recurrence, we analyzed the frequency of donor chimerism and the clinical course of post-OLT hepatitis C. MATERIAL AND METHODS We analyzed peripheral blood chimerism in 11 HCV-reinfected patients with post-HLA mismatched OLT. Patients were divided into 2 groups: the OLT chronic hepatitis C (CHC) group (n=8), exhibiting active hepatitis C recurrence; and the OLT-persistently normal ALT (PNALT) group (n=3), without active hepatitis...
March 24, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
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