Effect of donor genotype on patient survival after liver transplant: a retrospective cohort study.

Background: Several genetic variants are associated with chronic liver disease. The role of these variants in outcomes after liver transplantation (LT) is uncertain. The aim of this study was to determine if donor genotype at risk-associated variants in (rs738409 C>G, p.

Serological Response in Lung Transplant Recipients after Two Doses of SARS-CoV-2 mRNA Vaccines.

Background: Lung-transplant (LT) recipients are at high risk for COVID-19 due to immunosuppression and respiratory tropism of SARS-CoV-2. The information on the effect of COVID-19 mRNA vaccines to elicit immunogenic responses after a two-dose (2D) regimen in LT recipients is sparse. Thus, we assessed the effect of Pfizer-BioNTech and Moderna mRNA vaccines' 2D regimen on anti-spike responses in immunocompromised LT recipients.

SARS-CoV-2 Antibody Responses Do Not Predict COVID-19 Disease Severity.

Objectives: Initial reports indicate adequate performance of some serology-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assays. However, additional studies are required to facilitate interpretation of results, including how antibody levels impact immunity and disease course.

Methods: A total of 967 subjects were tested for IgG antibodies reactive to SARS-CoV-2, including 172 suspected cases of SARS-CoV-2, 656 plasma samples from healthy donors, 49 sera from patients with rheumatic disease, and 90 specimens from individuals positive for polymerase chain reaction (PCR)-based respiratory viral panel.

Allograft outcomes of treated children with kidney transplant who developed plasma cell-rich acute rejection (PCAR): A single center's experience.

Introduction: PCAR is a rare form of ACR that may compromise renal allografts. This review evaluates the outcomes of a protocol used to treat PCAR (Study group), and compares these outcomes with a matched cohort with ACR (Control group).

Methods: A retrospective analysis of 138 of pRTRs who underwent renal allograft biopsies between January 2008 and November 2016.

Evaluation of current strategies for surveillance and management of donor-specific antibodies: Single-center study.

Background: Although the presence of donor-specific antibodies (DSA) is known to impact lung allograft, limited data exist regarding DSA management.

Methods: We did a retrospective study at our center evaluating DSA management in adult lung transplant recipients undergoing lung transplantation between January 1, 2010 and June 30, 2014. Study follow-up was completed through October 2017.

Complement (C1q) Binding De Novo Donor-Specific Antibodies and Cardiac-Allograft Vasculopathy in Pediatric Heart Transplant Recipients.

Background: We hypothesized C1q binding de novo donor-specific antibody (DSA) after heart transplant (HT) is a higher risk for development of coronary artery vasculopathy (CAV) in children.

Methods: A retrospective analysis of 127 pediatric HT recipients transplanted between January 2005 and December 2014 was used to determine complement (C1q)-binding de novo DSA on the outcomes of HT and the ability of the C1q assay to predict CAV development.

Results: Of 127 patients, 59 (46.

Alemtuzumab (Campath-1H) therapy for refractory rejections in pediatric heart transplant recipients.

Despite substantial improvements in survival after pediatric heart transplantation, refractory rejection remains a major cause of morbidity and mortality. We have utilized ALE (Campath-1H) in six consecutive patients with refractory rejection. These rejection episodes persisted despite conventional treatment, which included intravenous methylprednisolone, rituximab, immunoglobulin G, and antithymocyte globulin.

Management of sensitized pediatric patients prior to renal transplantation.

Background: Data on renal allograft outcome in sensitized children are scarce. We report the clinical courses of four children who received desensitization therapy prior to renal transplantation in our institution.

Methods: Between 2009 and 2011, four pediatric patients with stage 5 chronic kidney disease received desensitization therapy due to: (1) positive donor-specific antibodies (DSA) and/or crossmatches with potential living donors, (2) more than three positive crossmatches with deceased donors or (3) high calculated panel-reactive antibody of >80 %.

Donor-specific HLA alloantibodies: Impact on cardiac allograft vasculopathy, rejection, and survival after pediatric heart transplantation.

Background: There is increasing evidence that donor-specific anti-HLA antibodies (DSA) are associated with poor outcomes after cardiac transplantation in adults, but data are limited in children. The objective of this study was to examine the development and consequences of de novo DSA in pediatric recipients of heart transplants.

Methods: We analyzed 105 pediatric patients who received heart transplants at our center from January 2002 to December 2012.

Child sexual abuse and women's sexual health: the contribution of CSA severity and exposure to multiple forms of childhood victimization.

Research studies have provided increasing evidence for the potential adverse impact of child sexual abuse on women's sexual health. The present study examined the association between child sexual abuse and sexual health while controlling for various forms of childhood victimization. Self-report questionnaires were administered to 889 young women from the province of Quebec.

Sexual health in women reporting a history of child sexual abuse.

Objective: The present study examined the association between child sexual abuse (CSA) and sexual health outcomes in young adult women. Maladaptive coping strategies and optimism were investigated as possible mediators and moderators of this relationship.

Method: Data regarding sexual abuse, coping, optimism and various sexual health outcomes were collected using self-report and computerized questionnaires with a sample of 889 young adult women from the province of Quebec aged 20-23 years old.

Pancreatic islets engineered with SA-FasL protein establish robust localized tolerance by inducing regulatory T cells in mice.

Allogeneic islet transplantation is an important therapeutic approach for the treatment of type 1 diabetes. Clinical application of this approach, however, is severely curtailed by allograft rejection primarily initiated by pathogenic effector T cells regardless of chronic use of immunosuppression. Given the role of Fas-mediated signaling in regulating effector T cell responses, we tested if pancreatic islets can be engineered ex vivo to display on their surface an apoptotic form of Fas ligand protein chimeric with streptavidin (SA-FasL) and whether such engineered islets induce tolerance in allogeneic hosts.

Induction of tolerance to cardiac allografts using donor splenocytes engineered to display on their surface an exogenous fas ligand protein.

The critical role played by Fas ligand (FasL) in immune homeostasis renders this molecule an attractive target for immunomodulation to achieve tolerance to auto- and transplantation Ags. Immunomodulation with genetically modified cells expressing FasL was shown to induce tolerance to alloantigens. However, genetic modification of primary cells in a rapid, efficient, and clinically applicable manner proved challenging.

Ex vivo expansion of CD4+CD25+FoxP3+ T regulatory cells based on synergy between IL-2 and 4-1BB signaling.

Naturally occurring CD4(+)CD25(+)FoxP3(+) T regulatory (Treg) cells require three distinct signals transduced via TCR, CD28, and IL-2R for their development and maintenance. These requirements served as the basis for several recently developed ex vivo expansion protocols that relied on the use of solid support-bound Abs to CD3 and CD28 in the presence of high dose IL-2. We report in this study that Treg cells up-regulate the expression of inducible costimulatory receptor 4-1BB in response to IL-2, and stimulation using this receptor via a novel form of 4-1BB ligand (4-1BBL) fused to a modified form of core streptavidin (SA-4-1BBL) was effective in expanding these cells up to 110-fold within 3 wk.

CD4+CD25+ T regulatory cells dominate multiple immune evasion mechanisms in early but not late phases of tumor development in a B cell lymphoma model.

Tumors use a complex set of direct and indirect mechanisms to evade the immune system. Naturally arising CD4(+)CD25(+)FoxP3(+) T regulatory (Treg) cells have been implicated recently in tumor immune escape mechanism, but the relative contribution of these cells to overall tumor progression compared with other immune evasion mechanisms remains to be elucidated. Using the A20 B cell lymphoma as a transplantable tumor model, we demonstrate that this tumor employs multiple direct (expression of immunoinhibitory molecule PD-L1, IDO, and IL-10, and lack of expression of CD80 costimulatory molecule) and indirect (down-regulation of APC function and induction of Treg cells) immune evasion mechanisms.

Senescent fibroblasts resist apoptosis by downregulating caspase-3.

In replicative senescence, cells undergo permanent exit from cell cycle traverse; this is traditionally thought to occur at the end of a culture's in vitro life span, after serial passaging. In general, the checkpoint for replicative senescence is found at the G(1)/S border, controlled by the modulation of a battery of proteins, typified by gaining inhibitors of cell cycle traverse, such as cyclin-dependent kinases or RB hyperphosphorylation, and losing pro-proliferation gene expressions such as c-fos, c-myc, and a cadre of proliferation-dependent kinases. Here, we present evidence that replicatively senescent fibroblasts are resistant to apoptotic death, associated with a lack of key enzyme activities, caspase-3 being the chief executioner.

Designer microarrays: from soup to nuts.

The recognition that multigene mechanisms control the pathways determining the aging process renders gene screening a necessary skill for biogerontologists. In the past few years, this task has become much more accessible, with the advent of DNA chip technology. Most commercially available microarrays are designed with prefixed templates of genes of general interest, allowing investigators little freedom of choice in attempting to focus gene screening on a particular thematic pathway of interest.

Establishing lymphoblastoid cell lines from frozen blood of extremely old individuals.

In population studies involving peripheral blood samples from nonagenarian and centenarian donors, the amount of biological material available for research is restricted, as only a few millilitres of blood can be obtained from extremely old donors without significantly compromising their health. Here we describe a protocol to immortalize small amounts of total frozen blood from extremely old donors (90+) using the Epstein-Barr virus, despite the low level of circulating B cells present in nonagenarian and centenarian blood samples. This methodology provides a unique way to maximize resources of biological material available for research.

Blood-sample processing for the study of age-dependent gene expression in peripheral blood mononuclear cells.

Although most new biogerontological studies seeking to identify longevity candidate genes and factors involved in successful human aging are population based, and likely to involve the collection of blood from extremely old individuals, to our knowledge no unified protocols have yet been published to describe a methodology permitting the simultaneous generation of different kinds of biological specimens derived from a single source of a very small volume of peripheral blood. Here we describe a method permitting the simultaneous generation of plasma, RNA, DNA, protein, fixed lymphocytes, and frozen blood aliquots from a single 10- to 30-ml blood sample obtained from donors of any age (10-102 years old), and we show that the quality and quantity of DNA, RNA, protein, and fixed lymphocytes obtained do not vary significantly with age. As is frequently observed, the older individuals have higher plasma proportions.

Identification of high caspase-3 mRNA expression as a unique signature profile for extremely old individuals.

Apoptosis, or programmed cell death, is important for maintaining tissue homeostasis, as it permits the elimination of damaged, functionless or unwanted cells. As we age, our immune system undergoes constant remodeling, during which age-associated changes in immune parameters, including decreased naïve and increased memory T cells, have been reported. However, excessive immune cell loss, rendering the elderly more vulnerable to infections, and inappropriate deletion of damaged or functionless lymphocytes, can contribute to the development of age-associated diseases.

Alterations in TNF- and IL-related gene expression in space-flown WI38 human fibroblasts.

Spaceflight, just like aging, causes profound changes in musculoskeletal parameters, which result in decreased bone density and muscular weakness. As these conditions decrease our ability to conduct long-term manned space missions, and increase bone frailty in the elderly, the identification of genes responsible for the apparition of these physiological changes will be of great benefit. Thus, we developed and implemented a new microarray approach to investigate the changes in normal WI38 human fibroblast gene expression that arise as a consequence of space flight.