Donor-derived cell-free DNA monitoring for early diagnosis of antibody-mediated rejection after kidney transplantation: a randomized trial.

Background And Hypothesis: Donor-derived cell-free DNA (dd-cfDNA) shows good diagnostic performance for the detection of antibody-mediated rejection (AMR) in kidney transplant recipients (KTR). However, the clinical benefits of dd-cfDNA monitoring need to be established. Early diagnosis of AMR at potentially reversible stages may be increasingly important due to emerging treatment options for AMR.

Predictors of graft failure after first detection of de novo donor-specific HLA antibodies in kidney transplant recipients.

Background: De novo donor-specific antibodies (dnDSAs) may cause antibody-mediated rejection and graft dysfunction. Little is known about the clinical course after first detection of dnDSAs during screening in asymptomatic patients. We aimed to assess the value of estimated glomerular filtration rate (eGFR) and proteinuria to predict graft failure in patients with dnDSAs and their potential utility as surrogate endpoints.

Identification of the activating cytotoxicity receptor NKG2D as a senescence marker in zero-hour kidney biopsies is indicative for clinical outcome.

The definition of biological donor organ age rather than chronological age seems obvious for the establishment of a valid pre-transplant risk assessment. Therefore, we studied gene expression for candidate markers in 60 zero-hour kidney biopsies. Compared with 29 younger donors under age 55, 31 elderly donors age 55 and older had significant mRNA expression for immunoproteasome subunits (PSMB8, PSMB9 and PSMB10), HLA-DRB, and transcripts of the activating cytotoxicity receptor NKG2D.

The activating receptor NKG2D of natural killer cells promotes resistance against enterovirus-mediated inflammatory cardiomyopathy.

In enterovirus-induced cardiomyopathy, information regarding the detailed impact of natural killer (NK) cells on the outcome of the disease is limited. We therefore hypothesized that NK cells and certain NK cell receptors determine the different outcome of coxsackievirus B3 (CVB3) myocarditis. Here, we demonstrate in murine models that resistance to chronic CVB3 myocarditis in immunocompetent C57BL/6 mice is characterized by significantly more mature CD11b(high) NK cells, the presence of NKG2D on NK cells, and enhanced NKG2D-dependent cytotoxicity compared to CVB3-susceptible A.

Induction of bona fide regulatory T cells after liver transplantation - the potential influence of polyclonal antithymocyte globulin.

T-cell-depleting strategies are an integral part of immunosuppressive regimens used in the hematological and solid organ transplant setting. Besides prevention of alloreactivity, treatment with rabbit antithymocyte globulin (rATG) has been related to the induction of immunoregulatory T cells (Treg) in vitro and in vivo. To investigate Treg induced by rATG, we prospectively studied the effect of rATG induction therapy in liver-transplanted recipients in vivo (n = 28).

Role of NK and NKT cells in solid organ transplantation.

In the context of solid organ transplantation, the exact interactions between the innate and adaptive alloimmune response have not yet been fully explored. In this transplant setting, natural killer (NK) cells have emerged as a particular focus of interest because of their ability to distinguish allogeneic major histocompatibility complex (MHC) antigens and their potent cytolytic activity. Based on this observation and its potential clinical relevance, NK cells have recently been shown to participate in the immune response in both acute and chronic rejection of solid organ allografts.

Targeting of natural killer cells by rabbit antithymocyte globulin and campath-1H: similar effects independent of specificity.

T cell depleting strategies are an integral part of immunosuppressive regimens widely used in the hematological and solid organ transplant setting. Although it is known to induce lymphocytopenia, little is known about the effects of the polyclonal rabbit antithymocyte globulin (rATG) or the monoclonal anti-CD52 antibody alemtuzumab on Natural Killer (NK) cells in detail. Here, we demonstrate that induction therapy with rATG following kidney/pancreas transplantation results in a rapid depletion of NK cells.

Quantitative DNA methylation analysis of FOXP3 as a new method for counting regulatory T cells in peripheral blood and solid tissue.

Regulatory T-cells (Treg) have been the focus of immunologic research due to their role in establishing tolerance for harmless antigens versus allowing immune responses against foes. Increased Treg frequencies measured by mRNA expression or protein synthesis of the Treg marker FOXP3 were found in various cancers, indicating that dysregulation of Treg levels contributes to tumor establishment. Furthermore, they constitute a key target of immunomodulatory therapies in cancer as well as transplantation settings.

SHIP limits immunoregulatory capacity in the T-cell compartment.

Regulatory T cells (T(regs)) play a pivotal role in preventing autoimmunity, graft-versus-host disease (GVHD), and organ graft rejection. We previously showed that either germline or induced SH2 domain-containing inositol 5-phosphatase (SHIP) deficiency in the host abrogates GVHD. Here we show that SHIP deficiency promotes an increase of CD4(+)CD25(+)FoxP3(+) T(regs) and CD4(+)CD25(-)FoxP3(+)"naive" T cells in the periphery that display increased CD103, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), OX40, and FcgammaRII/III expression.

Angiotensin II induction of fibronectin biosynthesis in cultured human mesangial cells: association with CREB transcription factor activation.

We assessed the effect of angiotensin II on fibronectin biosynthesis a nd transcription factor activation in adult human mesangial cells in culture. We found that 10(-5) mol/L angiotensin II tended to increase fibronectin mRNA expression within 1 hour (1.2-fold +/- 0.

Duchenne muscular dystrophy: a case with prolonged survival.

We report the case of a patient with confirmed Duchenne muscular dystrophy who lived a useful and improved life until age 34. He was first seen in our Muscular Dystrophy Clinic when he was 14; at that time he was functionally quadriplegic and required assistance for all activities of daily living. At age 17, ventilatory insufficiency developed and the patient was provided with a positive pressure device (mouthpiece) to augment his ventilation.

Mechanical ventilation of patients with late stage Duchenne muscular dystrophy: management in the home.

Death in the late stage of Duchenne muscular dystrophy is most frequently a consequence of respiratory failure. Since muscles of ventilation become weakened the bellows mechanism fails insidiously. Patients exhibit symptoms of ventilatory insufficiency, the first to be noticed are those associated with CO2 retention: dyspnea, nightmares, increased heart rate, and increased blood pressure.