Torque Teno Virus Load Predicts Opportunistic Infections after Kidney Transplantation but Is Not Associated with Maintenance Immunosuppression Exposure.

Measuring the non-pathogenic Torque Teno Virus (TTV) load allows assessing the net immunosuppressive state after kidney transplantation (KTx). Currently, it is not known how exposure to maintenance immunosuppression affects TTV load. We hypothesized that TTV load is associated with the exposure to mycophenolic acid (MPA) and tacrolimus.

Lower Time in Therapeutic Range Relates to a Worse Kidney Graft Outcome.

Tacrolimus has a narrow therapeutic margin. Maintaining tacrolimus blood levels in the appropriate range is difficult because of its intrapatient variability. In fact, greater blood level variability has been related to worse kidney graft outcome, but only measuring variability does not consider the therapeutic range goal.

Within-Patient Variability in Tacrolimus Blood Levels Predicts Kidney Graft Loss and Donor-Specific Antibody Development.

Background: Lack of adherence to immunosuppressive drugs is a risk factor for development of de novo donor-specific antibodies (dnDSA) and can contribute to antibody-mediated rejection and graft loss. Moreover, nonadherence is the main determinant of immunosuppressive drug level variability. High intrapatient variability of tacrolimus relates to a worse outcome in transplant recipients through unknown mechanisms.

High proportion of pretransplantation activated regulatory T cells (CD4+CD25highCD62L+CD45RO+) predicts acute rejection in kidney transplantation: results of a multicenter study.

Background: Prognostic biomarkers of acute rejection (AR) in solid organ transplantation have been addressed in multiple small retrospective studies, and there is a critical need for multicenter studies. Because of their tolerogenic properties, regulatory T cells (Tregs) play an important role in transplant outcome.

Methods: In the present multicenter study, we have retrospectively examined different Treg subpopulations in an independent cohort of kidney transplant patients within first year after kidney transplantation.

Peptide-loaded Langerhans cells, despite increased IL15 secretion and T-cell activation in vitro, elicit antitumor T-cell responses comparable to peptide-loaded monocyte-derived dendritic cells in vivo.

Purpose: We compared the efficacy of human Langerhans cells (LC) as tumor immunogens in vivo with monocyte-derived dendritic cells (moDC) and investigated how interleukin 15 (IL15) supports optimal DC-stimulated antitumor immunity.

Experimental Design: American Joint Committee on Cancer stage III/IV melanoma patients participated in this first clinical trial comparing melanoma peptide-pulsed LC with moDC vaccines (NCT00700167, www.ClinicalTrials.

Evolution of tacrolimus blood levels and concentration-dose ratios in patients who develop new onset diabetes mellitus after kidney transplantation.

New onset diabetes mellitus (NODM) affects kidney transplantation outcome. Several risk factors, including immunosuppressive drug levels, are related with NODM development. This analysis evaluates the incidence and risk factors of NODM in kidney transplant patients receiving tacrolimus, taking into account 6-month blood levels and concentration-dose ratios (CDRs).

Modulation of autoantibody production by mycophenolate mofetil: effects on the development of SLE in (NZB x NZW)F1 mice.

Background: Mycophenolate mofetil (MMF) has been successfully used to improve or prevent the development of systemic lupus erythematosus (SLE) in both humans and in several lupus-prone mice. In the present study, we evaluated mechanisms through which MMF may exert its therapeutic effect on the development of systemic autoimmunity.

Methods: (NZBxNZW)F(1) female mice were continuously treated with 100 mg/kg/day (high dose) or 30 mg/kg/day (low dose) MMF beginning at 3 months of age.