Formation of donor-specific antibodies depends on the epitope load of mismatched HLAs in lung transplant recipients: A retrospective single-center study.

The development of donor-specific antibodies (DSA) has a significant impact on graft outcome in solid organ transplantation. Mismatched HLAs are recognized directly and indirectly by the recipient immune system. Both pathways occur in parallel and result in the generation of plasma cells, DSA, cytotoxic and T helper lymphocytes.

Pretransplant HLA typing revealed loss of heterozygosity in the major histocompatibility complex in a patient with acute myeloid leukemia.

Introduction: Chromosomal abnormalities are frequent events in hematological malignancies. The degree of HLA compatibility between donor and recipient in hematopoietic stem cell transplantation is critical.

Purpose Of The Study: In this report, we describe an acute myeloid leukemia case with loss of heterozygosity (LOH) encompassing the entire HLA.

Class II Human Leukocyte Antigen Epitope Mismatch Predicts De Novo Donor-Specific Antibody Formation After Liver Transplantation.

Formation of de novo donor-specific antibodies (dn-DSAs) has been associated with longterm immunologic complications after liver transplantation (LT). We hypothesized that human leukocyte antigen (HLA) epitope/eplet mismatch (MM) is a marker of immunogenicity and a risk factor for dn-DSA formation. Sera from 80 LT recipients were prospectively screened for dn-DSA by a Luminex single-antigen test (One Lambda, Inc.

Rapid and strong de novo donor-specific antibody development in a lung transplant recipient: Short communication/case report.

A 66-yo female patient (typed B*39:01, 44:02) underwent first left single lung transplant (typed B*81:01, 15:17) on 02/07/2016 with negative for DSA in current and historical samples. On 02/17/2016 strong de novo DSA (MFI=15,200, C1q+) to B81 were detected. The recipient has two children typed B*07:02, 44:02 B*27:03, 39:01, and had received multiple vaccinations.

Prospective Monitoring of Donor-specific Anti-HLA Antibodies After Intestine/Multivisceral Transplantation: Significance of De Novo Antibodies.

Background: Presence of circulating donor-specific antibodies (DSA) may be associated with worse clinical outcomes after intestine/multivisceral transplantation.

Methods: In 79 intestine/multivisceral recipients, sera were prospectively screened for DSA by Luminex Single antigen test at 1, 3, 6, 9, 12, 18, 24, and 36 months after transplantation. Standard immunosuppression included thymoglobulin-rituximab induction and tacrolimus-prednisone maintenance.

Meningeal relationships to the spinal nerves and rootlets: a gross, histological, and radiological study with application to intradural extramedullary spinal tumors.

Introduction: Juxtapositional tumors of the spinal nerve roots have been noted to not only interact with the roots at various vertebral levels, but also differ among patients. Therefore, the aim of the current study was to elucidate the potential for variation among the relationships of the meningeal layers at different nerve levels.

Methods: In 20 unembalmed adult cadavers and five fetal specimens, the spinal nerve roots from the cervical, thoracic, and lumbar regions were harvested with their associated meningeal layers and subjected to microdissection, histological analysis, or radiological imaging using 9.

Methodological aspects of anti-human leukocyte antigen antibody analysis in solid organ transplantation.

Donor human leukocyte antigen (HLA)-specific antibodies (DSA) play an important role in solid organ transplantation. Preexisting IgG isotype DSA are considered a risk factor for antibody mediated rejection, graft failure or graft loss. The post-transplant development of DSA depends on multiple factors including immunogenicity of mismatched antigens, HLA class II typing of the recipient, cytokine gene polymorphisms, and cellular immunoregulatory mechanisms.

Crossmatch-positive liver transplantation in patients receiving thymoglobulin-rituximab induction.

Background: Positive crossmatch (CM) in liver transplantation (LT) is associated with worse outcomes. Role of induction immunosuppression in this setting remains to be studied.

Methods: One thousand consecutive LT patients receiving rabbit antithymocyte globulin±rituximab induction were studied.

Analysis of anti-HLA antibodies in sensitized kidney transplant candidates subjected to desensitization with intravenous immunoglobulin and rituximab.

Background: Preexisting donor-specific antibodies against human leukocyte antigens are major risk factors for acute antibody-mediated and chronic rejection of kidney transplant grafts. Immunomodulation (desensitization) protocols may reduce antibody concentration and improve the success of transplant. We investigated the effect of desensitization with intravenous immunoglobulin and rituximab on the antibody profile in highly sensitized kidney transplant candidates.

The effectiveness of the combination of rituximab and high-dose immunoglobulin in the immunomodulation of sensitized kidney transplant candidates.

Kidney transplantation faces many challenges not the least of which is the presence of pre-formed HLA antibodies. At our institution, we have used a combination of methods to immunomodulate sensitized patients. Most recently, this has been attempted with a combination of immunoglobulin (IVIG) and rituximab (Rituxan; Genetech, CA, USA).

Impact of positive flow cytometry crossmatch on outcomes of intestinal/multivisceral transplantation: role anti-IL-2 receptor antibody.

Background: Positive crossmatch may be associated with an increased risk of acute rejection (AR) and worse overall outcomes after intestinal/multivisceral (MV) transplantation. However, the evidence from published studies in this setting is sparse and contradictory. This study reports the impact of positive flow cytometry crossmatch on clinical outcomes after intestinal/MV transplantation and the use of anti-interleukin (IL)-2 receptor antibody as a maintenance immunosuppressant.

Early findings of prospective anti-HLA donor specific antibodies monitoring study in pancreas transplantation: Indiana University Health Experience.

The significance of donor-specific antibodies (DSA) is not well known in the setting of pancreas transplantation. Since December 2009, we prospectively followed pancreas transplant patients with single-antigen-luminex-bead testing at one, two, three, six, and then every six months for the first two yr. Thirty-five of the 92 patients that underwent pancreas transplantation (13 pancreas-alone [PTA], 20 with a kidney [SPK], and two after a kidney [PAK]) agreed to participate in study.

Role for a conserved structural motif in assembly of a class I aminoacyl-tRNA synthetase active site.

The catalytic domains of class I aminoacyl-tRNA synthetases are built around a conserved Rossmann nucleotide binding fold, with additional polypeptide domains responsible for tRNA binding or hydrolytic editing of misacylated substrates. Structural comparisons identified a conserved motif bridging the catalytic and anticodon binding domains of class Ia and Ib enzymes. This stem contact fold (SCF) has been proposed to globally orient each enzyme's cognate tRNA by interacting with the inner corner of the L-shaped tRNA.

Early steroid withdrawal in repeat kidney transplantation.

Background And Objectives: Kidney re-transplantation (KRT) candidates are considered at high risk for graft failure. Most of these patients are kept on a chronic steroid maintenance (CSM) regimen. The safety of early steroid withdrawal (ESW) remains unanswered in KRT.

The strength of donor-specific antibody is a more reliable predictor of antibody-mediated rejection than flow cytometry crossmatch analysis in desensitized kidney recipients.

The aim of this study was to evaluate the utility of donor-specific antibodies (DSA) and flow cytometry crossmatch (FCCM) as tools for predicting antibody-mediated rejection (AMR) in desensitized kidney recipients. Sera from 44 patients with DSA at the time of transplant were reviewed. Strength of DSA was determined by single antigen Luminex bead assay and expressed as mean fluorescence intensity (MFI).

Tolerance induced by anti-CD3 immunotoxin plus 15-deoxyspergualin associates with donor-specific indirect pathway unresponsiveness.

Peritransplant treatment with anti-CD3 immunotoxin plus deoxyspergualin induces tolerance to kidney allografts in most rhesus macaque recipients. Tolerant recipients maintain normal function for years without evidence of chronic rejection. Indirect alloantigen presentation is implicated in chronic rejection.

Immune cell function testing: an adjunct to therapeutic drug monitoring in transplant patient management.

Each year, 55 000 organ transplants are performed worldwide. Cumulatively, the number of living organ recipients is now estimated to be over 300 000. Most of these transplant recipients will remain on immunosuppressive drugs for the remainder of their lives to prevent rejection episodes.

Stable alpha- and beta-islet cell function after tolerance induction to pancreatic islet allografts in diabetic primates.

Pancreatic islet transplantation (PIT) is an attractive alternative for type 1 diabetic patients. PIT is not yet an effective clinical reality due in part to early loss of functional islet mass. In addition, current immunosuppressive drugs have toxic effects on islets and increase the risk of morbidity and mortality.