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Robert Ettenger, Hyunsook Chin, Karen Kesler, Nancy Bridges, Paul Grimm, Elaine F Reed, Minnie Sarwal, Richard Sibley, Eileen Tsai, Barry Warshaw, Allan D Kirk
The Immune Development in Pediatric Transplantation (IMPACT) study was conducted to evaluate relationships between alloimmunity, protective immunity, immune development, physical parameters and clinical outcome in children undergoing kidney transplantation. We prospectively evaluated biopsy-proven acute rejection (BPAR), de novo donor specific antibody (dnDSA) formation, viremia, viral infection, T cell immunophenotyping and BMI/weight Z scores in the first year post-transplant in 106 pediatric kidney transplant recipients...
December 18, 2016: American Journal of Transplantation
C A Schinstock, F Cosio, W Cheungpasitporn, D M Dadhania, M J Everly, M D Samaniego-Picota, L Cornell, M D Stegall
De novo donor specific antibody (dnDSA) is associated with antibody mediated rejection (AMR) and allograft loss, yet the allograft histology associated with dnDSA remains unclear. The aim of this study was to examine the allograft histology associated with dnDSA in patients with serial surveillance biopsies. We retrospectively studied adult conventional solitary kidney transplant recipients from 10/2007-5/2014. DnDSA was new DSA with MFI >1000. The incidence of dnDSA was 7.0%(54/771) over mean follow-up of 4...
December 15, 2016: American Journal of Transplantation
Alexis Chenouard, Mélanie Chesneau, Linh Bui Nguyen, Sabine Le Bot, Marion Cadoux, Emilie Dugast, Chloé Paul, Stéphanie Malard-Castagnet, Simon Ville, Pierrick Guérif, Jean-Paul Soulillou, Nicolas Degauque, Richard Danger, Magali Giral, Sophie Brouard
Renal operationally tolerant patients (TOL) display a defect in B cell differentiation, with a deficiency in plasma cells. Recently described, T follicular helper cells (Tfh) play a critical role in B cell differentiation. We analyzed blood Tfh subsets in TOL and transplanted patients with stable graft function under immunosuppression (STA). We observed a reduced proportion of blood activated and highly functional Tfh subsets in TOL, without affecting Tfh absolute numbers. Functionally, Tfh from TOL displayed a modified gene expression profile, failed to produce IL-21 and were unable to induce IgG production by naive B cells...
November 26, 2016: American Journal of Transplantation
C Wiebe, A J Gareau, D Pochinco, I W Gibson, J Ho, P E Birk, T Blydt-Hasen, M Karpinski, A Goldberg, L Storsley, D N Rush, P W Nickerson
De novo donor-specific antibodies (dnDSAs) that develop after renal transplantation are independent predictors of allograft loss. However, it is unknown if dnDSA C1q status or titer at the time of first detection can independently predict allograft loss. In a consecutive cohort of 508 renal transplant recipients, 70 developed dnDSAs. Histologic and clinical outcomes were correlated with the C1q assay or dnDSA titer. C1q positivity correlated with dnDSA titer (p < 0.01) and mean fluorescence intensity (p < 0...
August 19, 2016: American Journal of Transplantation
A Nocera, A Tagliamacco, M Cioni, A Innocente, I Fontana, G Barbano, A Carrea, M Ramondetta, A Sementa, S Basso, G Quartuccio, C Klersy, M Bertocchi, E Verrina, G Garibotto, G M Ghiggeri, M Cardillo, P Comoli, F Ginevri
Donor-specific HLA antibody (DSA)-mediated graft injury is the major cause of kidney loss. Among DSA characteristics, graft homing has been suggested as an indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA) graft homing on kidney transplantation outcome. Graft biopsy specimens and parallel sera from 48 nonsensitized pediatric kidney recipients were analyzed. Serum samples and eluates from graft biopsy specimens were tested for the presence of dnDSAs with flow bead technology. Intragraft dnDSAs (gDSAs) were never detected in the absence of serum dnDSAs (sDSAs), whereas in the presence of sDSAs, gDSAs were demonstrated in 72% of biopsy specimens...
August 8, 2016: American Journal of Transplantation
Christopher F Bryan, Vimal Chadha, Bradley A Warady
It is now appreciated that more HLA-DR mismatching at the time of the first renal transplant is associated with higher degrees of sensitization, lower rates and longer times to retransplantation, and worse graft outcomes in children who are subsequently retransplanted. As such, our pediatric renal transplant program preferentially uses 0 or 1 HLA-DR-mismatched kidneys and reserves 2 DR-mismatched kidneys for recipients with an eminent need for a kidney. Based on a new HLA class II epitope matching strategy that is designed to minimize dnDSA production to DR and DQ antigens, we evaluated the prevalence of DR and DQ eplet mismatching for dd offers made to our pediatric wait-listed candidates...
July 22, 2016: Pediatric Transplantation
Samir J Patel, Wadi N Suki, Jennifer Loucks-DeVos, Edward A Graviss, Duc T Nguyen, Richard J Knight, Samantha A Kuten, Linda W Moore, Larry D Teeter, Lillian W Gaber, A Osama Gaber
Lymphocyte-depleting induction lowers acute rejection (AR) rates among high-immunologic risk (HIR) renal transplant recipients, including African Americans (AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dnDSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin (ATG) induction and triple maintenance immunosuppression...
August 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Clara García-Carro, Christina Dörje, Anders Åsberg, Karsten Midtvedt, Helge Scott, Finn P Reinholt, Hallvard Holdaas, Daniel Seron, Anna V Reisæter
BACKGROUND: Interstitial fibrosis and tubular atrophy (IFTA) associated with interstitial inflammation in nonscarred areas (IFTA+i) is associated with poorer graft outcome than inflammation without IFTA or IFTA without inflammation. METHODS: We evaluated if histological categories at week 6 could predict the development of interstitial fibrosis and de novo donor specific anti-HLA antibodies (dnDSA) at 1 year. Biopsies were classified according to Banff criteria as normal (i+t≤1 and ci+ct≤1), inflammation (i+t≥2 and ci+ct≤1), IFTA (i+t≤1 and ci+ct≥2) or IFTA+i (i+t≥2 and ci+ct≥2)...
May 10, 2016: Transplantation
B A Kiberd, A Miller, S Martin, K K Tennankore
Screening for de novo donor specific antibodies (dnDSA) in stable kidney transplant recipients is routine practice in some centers. Patients with DSA are at increased risk of graft loss and early intervention may improve outcomes. However the costs and benefits of dnDSA surveillance are unknown. A medical decision analysis to examine a screening strategy was developed for kidney transplant recipients who had stable graft function and were DSA negative 1 year post transplant. In the base case, a modest 25% reduction in graft loss in dnDSA positive patients treated with increased immunosuppression resulted in 0...
April 23, 2016: American Journal of Transplantation
Jussi M Tikkanen, Lianne G Singer, S Joseph Kim, Yanhong Li, Matthew Binnie, Cecilia Chaparro, Chung-Wai Chow, Tereza Martinu, Sassan Azad, Shaf Keshavjee, Kathryn Tinckam
RATIONALE: Despite increasing evidence about the role of donor-specific human leukocyte antigen (HLA) antibodies in transplant outcomes, the incidence and impact of de novo donor-specific antibodies (dnDSA) after lung transplantation remains unclear. OBJECTIVES: To describe the incidence, characteristics, and impact of dnDSA after lung transplantation. METHODS: We investigated a single-center cohort of 340 lung transplant recipients undergoing transplant during 2008 to 2011...
September 1, 2016: American Journal of Respiratory and Critical Care Medicine
Julio Pascual, Andreas Zuckermann, Arjang Djamali, Alexandre Hertig, Maarten Naesens
The mode of action of rabbit antithymocyte globulin (rATG) includes preferential inhibition of pre-existing donor-reactive memory T-cell reconstitution and possibly apoptosis of plasma cells, the source of donor specific antibodies (DSAs). In kidney transplant patients with low-strength preformed DSAs, non-comparative data have shown a low incidence of antibody-mediated rejection (ABMR) and graft survival using rATG even without desensitization procedures. For high strengths of preformed DSAs, rATG induction with more aggressive desensitization appears effective, with mixed results concerning the addition of B-cell specific agents...
April 2016: Transplantation Reviews
P Comoli, M Cioni, A Tagliamacco, G Quartuccio, A Innocente, I Fontana, A Trivelli, A Magnasco, A Nocco, C Klersy, L Rubert, M Ramondetta, M Zecca, G Garibotto, G M Ghiggeri, M Cardillo, A Nocera, F Ginevri
Alloantibody-mediated graft injury is a major cause of kidney dysfunction and loss. The complement-binding ability of de novo donor-specific antibodies (dnDSAs) has been suggested as a prognostic tool to stratify patients for clinical risk. In this study, we analyzed posttransplant kinetics of complement-fixing dnDSAs and their role in antibody-mediated rejection development and graft loss. A total of 114 pediatric nonsensitized recipients of first kidney allograft were periodically monitored for dnDSAs using flow bead assays, followed by C3d and C1q assay in case of positivity...
July 2016: American Journal of Transplantation
Jacqueline G OʼLeary, Millie Samaniego, Marta Crespo Barrio, Luciano Potena, Adriana Zeevi, Arjang Djamali, Emanuele Cozzi
Production of de novo donor-specific antibodies (dnDSA) is a major risk factor for acute and chronic antibody-mediated rejection and graft loss after all solid organ transplantation. In this article, we review the data available on the risk of individual immunosuppressive agents and their ability to prevent dnDSA production. Induction therapy with rabbit antithymocyte globulin may achieve a short-term decrease in dnDSA production in moderately sensitized patients. Rituximab induction may be beneficial in sensitized patients, and in abrogating rebound antibody response in patients undergoing desensitization or treatment for antibody-mediated rejection...
January 2016: Transplantation
G Dieplinger, M J Everly, K P Briley, C E Haisch, P Bolin, A Q Maldonado, W T Kendrick, S A Kendrick, C Morgan, P I Terasaki, L M Rebellato
BACKGROUND: BK polyomavirus (BKPyV) viremia/nephropathy and reduction in immunosuppression following viremia may increase the risk of alloimmune activation and allograft rejection. This study investigates the impact of BKPyV viremia on de novo donor anti-human leukocyte antigen (HLA)-specific antibodies (dnDSA). PATIENTS AND METHODS: All primary renal transplants at East Carolina University from March 1999 to December 2010, with at least 1 post-transplant BKPyV viral load testing, were analyzed...
December 2015: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Ronald P Pelletier, Amer A Rajab, Alejandro Diez, Nicholas R DiPaola, Ginny L Bumgardner, Elmahdi A Elkhammas, Mitchell L Henry
BACKGROUND: De novo donor-specific antibodies (dnDSA) post-transplant correlate with a higher risk of immunologic graft injury and loss following kidney and pancreas transplantation. Post-transplant dnDSA can occur within the first post-transplant year. METHODS: In this study, 817 of 1290 kidney and simultaneous kidney/pancreas recipients were tested for dnDSA post-transplant. Recipient immunosuppressive treatment at one, three, six, and 12 months post-transplant was correlated with dnDSA incidence by univariate and multivariate analyses...
December 2015: Clinical Transplantation
Maria Messina, Claudia Ariaudo, Loredana Praticò Barbato, Silvia Beltramo, Gianna Mazzucco, Antonio Amoroso, Andrea Ranghino, Vincenzo Cantaluppi, Fabrizio Fop, Giuseppe Paolo Segoloni, Luigi Biancone
BACKGROUND: The C1q-binding properties of donor specific antibodies (DSA) may be related to antibody-mediated rejection and poor outcome. METHODS: We retrospectively studied 35 kidney transplant recipients with transplant glomerulopathy (TG) and de novo DSA (dnDSA). C1q dnDSA were measured in the serum stored at renal biopsy and the association among C1q-fixing dnDSA, C4d deposition and graft loss was examined. RESULTS: Of the 35 patients with dnDSA and TG, 15 (42...
September 2015: Transplant Immunology
C Wiebe, I W Gibson, T D Blydt-Hansen, D Pochinco, P E Birk, J Ho, M Karpinski, A Goldberg, L Storsley, D N Rush, P W Nickerson
Understanding rates and determinants of clinical pathologic progression for recipients with de novo donor-specific antibody (dnDSA), especially subclinical dnDSA, may identify surrogate endpoints and inform clinical trial design. A consecutive cohort of 508 renal transplant recipients (n = 64 with dnDSA) was studied. Recipients (n = 388) without dnDSA or dysfunction had an eGFR decline of -0.65 mL/min/1.73 m(2) /year. In recipients with dnDSA, the rate eGFR decline was significantly increased prior to dnDSA onset (-2...
November 2015: American Journal of Transplantation
Edoardo Melilli, Elena Crespo, Diego Sandoval, Anna Manonelles, Neus Sala, Richard Mast, Ariadna Padulles, Josep M Grinyo, Oriol Bestard, Josep Maria Cruzado
The use of generic formulations of immunosuppressive drugs in renal transplantation has been and still is a controversial subject. The lack of clinical studies about safety and efficacy in transplant patients is one of the factors restricting the diffusion of generic drugs in the renal transplant field. Since March 2013, our transplant unit has incorporated generic tacrolimus (Adoport(®) ; Sandoz), replacing the one we were currently using (Prograf(®) ; Astellas). When carrying out our retrospective analysis comparing the two different formulations, we evaluated several clinical results: tacrolimus trough concentrations (C0) at 5-7 days; 1, 3, and 6 months post-transplantation; concentration/dose ratio at 6 months; acute rejection incidence; delayed graft function (DGF); renal function (as CKD-EPI); and proteinuria at 6 months in 120 patients (1:1 ratio of Prograf(®) versus Adoport(®) ), noticing no important differences...
November 2015: Transplant International: Official Journal of the European Society for Organ Transplantation
S Shabir, J Girdlestone, D Briggs, B Kaul, H Smith, S Daga, S Chand, S Jham, C Navarrete, L Harper, S Ball, R Borrows
Recent cross-sectional studies suggest an important role for transitional B lymphocytes (CD19 + CD24hiCD38hi) in promoting transplant tolerance, and protecting from late antibody-mediated rejection (ABMR). However, prospective studies are lacking. This study enrolled 73 de novo transplant recipients, and collected serial clinical, immunological and biochemical information over 48 ± 6 months. Cell phenotyping was conducted immediately prior to transplantation, and then on five occasions during the first year posttransplantation...
May 2015: American Journal of Transplantation
Jin Zheng, Wujun Xue, Xin Jing, Jun Hou, Xiaohui Tian, Puxun Tian, Xiaoming Ding, Xiaoming Pan, Hang Yan, Xinshun Feng, Heli Xiang, Yang Li, Chenguang Ding
BACKGROUND: The aim of the present study is to investigate the impact of de novo donor-specific antibodies (dnDSA) on early graft function, to provide objective reference for early clinical diagnosis and reasonable individualized treatment. METHODS: 305 cases of renal transplant patients for the first time were observed in this study. Follow-up time for all recipients was 6 months after operation. HLA antibody, DSA, renal function were monitored after transplant...
April 2015: Renal Failure
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