Optimized immunosuppression to prevent graft failure in renal transplant recipients with HLA antibodies (OuTSMART): a randomised controlled trial.

Background: 3% of kidney transplant recipients return to dialysis annually upon allograft failure. Development of antibodies (Ab) against human leukocyte antigens (HLA) is a validated prognostic biomarker of allograft failure. We tested whether screening for HLA Ab, combined with an intervention to improve adherence and optimization of immunosuppression could prevent allograft failure.

A multicenter randomized controlled trial indicates that paclitaxel-coated balloons provide no benefit for arteriovenous fistulas.

The role of paclitaxel-coated balloons has been established in the coronary and peripheral arterial circulations with recent interest in the use of paclitaxel-coated balloons to improve patency rates following angioplasty of arteriovenous fistulas. To assess the efficacy of paclitaxel-coated angioplasty balloons to prolong the survival time of target lesion primary patency in arteriovenous fistulas, we designed an investigator-led multi-center randomized controlled trial with follow up time variable for a minimum of one year. Patients with an arteriovenous fistula who were undergoing an angioplasty for a clinical indication were included but patients with one or more lesions outside the treatment segment were excluded.

Update to the study protocol, including statistical analysis plan, for the multicentre, randomised controlled OuTSMART trial: a combined screening/treatment programme to prevent premature failure of renal transplants due to chronic rejection in patients with HLA antibodies.

Background: Chronic rejection is the single biggest cause of premature kidney graft failure. HLA antibodies (Ab) are an established prognostic biomarker for premature graft failure so there is a need to test whether treatment decisions based on the presence of the biomarker can alter prognosis. The Optimised TacrolimuS and MMF for HLA Antibodies after Renal Transplantation (OuTSMART) trial combines two elements.

Start2quit: a randomised clinical controlled trial to evaluate the effectiveness and cost-effectiveness of using personal tailored risk information and taster sessions to increase the uptake of the NHS Stop Smoking Services.

Background: The NHS Stop Smoking Services (SSSs) offer help to smokers who want to quit. However, the proportion of smokers attending the SSSs is low and current figures show a continuing downward trend. This research addressed the problem of how to motivate more smokers to accept help to quit.

Can a combined screening/treatment programme prevent premature failure of renal transplants due to chronic rejection in patients with HLA antibodies: study protocol for the multicentre randomised controlled OuTSMART trial.

Background: Renal transplantation is the best treatment for kidney failure, in terms of length and quality of life and cost-effectiveness. However, most transplants fail after 10 to 12 years, consigning patients back onto dialysis. Damage by the immune system accounts for approximately 50% of failing transplants and it is possible to identify patients at risk by screening for the presence of antibodies against human leukocyte antigens.

T cell targeted strategies for improved efficacy and safety of specific immunotherapy for allergic disease.

Allergic diseases including asthma, rhinitis and eczema are known to be a major health and economic burden worldwide. Specific immunotherapy (SIT) is potentially curative but restricted in use, e.g.

Unique and cross-reactive T cell epitope peptides of the major Bahia grass pollen allergen, Pas n 1.

Background: Bahia grass pollen (BaGP) is a major cause of allergic rhinitis. Subcutaneous allergen-specific immunotherapy is effective for grass pollen allergy, but is unsuitable for patients with moderate to severe asthma due to the risk of anaphylaxis. T cell-reactive but IgE nonreactive peptides provide a safer treatment option.

Functional regulatory T cells and allergen immunotherapy.

Purpose Of Review: Burgeoning literature ascribing roles for regulatory T cells (Treg) in controlling clinical allergy frequently relies on phenotypic markers rather than functional suppression assays. This review examines evidence for functional Treg in controlling immune responses to allergen with particular focus on allergen-specific immunotherapy.

Recent Findings: Over the last year, use of recently identified Treg markers has facilitated more precise delineation and isolation of Treg subtypes.

House dust mite sublingual immunotherapy: the role for transforming growth factor-beta and functional regulatory T cells.

Rationale: Sublingual allergen-specific immunotherapy is gaining popularity for treatment of allergic diseases, but underlying immunological mechanisms are unresolved.

Objectives: To perform detailed immunological investigation of sublingual house dust mite (HDM) immunotherapy.

Methods: A 12-month randomized double-blind placebo-controlled study of sublingual HDM immunotherapy in 30 HDM-allergic subjects was performed, with 1-year open extension in 9 patients on active treatment.

Allergen-related approaches to immunotherapy.

Allergic diseases, including asthma, rhinitis and eczema, represent a major health burden worldwide. Mainstay treatments are allergen avoidance where feasible and pharmacotherapy for symptom relief. For selected patients, allergen-specific immunotherapy (SIT) offers the prospect of long lasting clinical efficacy.

Cutting edge: Notch signaling induces a distinct cytokine profile in dendritic cells that supports T cell-mediated regulation and IL-2-dependent IL-17 production.

Recently it has been shown that dendritic cells (DC) express both Notch and Notch ligands, allowing for the possibility that Notch signaling may influence their maturation. We show that although both Jagged (Jgd) and Delta-like (DlL) ligands were able to activate the canonical Notch pathway in mouse DC, only Jgd1 could induce the production of certain cytokines. Maturation of DC via Jgd1 resulted in an entirely different maturation program from that induced through TLR (via LPS) signaling, promoting the production of high levels of IL-2 and IL-10.

Secretion of IFN-gamma and not IL-2 by anergic human T cells correlates with assembly of an immature immune synapse.

We report differences in the supramolecular organization of the immunologic synapse (IS) formed by resting and anergic human T cells with agonist peptide-loaded antigen-presenting cells (APCs). T cells reactive to influenza A hemagglutinin peptide or Fel d 1 peptide 4 were rendered both anergic and regulatory by incubation with high doses of agonist peptide in the absence of APCs. At the IS between resting T cells and peptide-loaded APCs, both CD3epsilon and CD3zeta initially accumulate within a ring or arc before redistributing within 30 minutes to single or multiple foci more central to the contact.

High dose allergen stimulation of T cells from house dust mite-allergic subjects induces expansion of IFN-gamma+ T Cells, apoptosis of CD4+IL-4+ T cells and T cell anergy.

Background: During clinically effective allergen-specific immunotherapy a shift in cytokine dominance from IL-4, IL-5 predominant to IFN-gamma predominant has been observed. As antigen concentration influences Th cell priming, this study aimed to determine the effect of different allergen concentrations on human house dust mite (HDM)-specific T cell production of IL-4 and IFN-gamma, proliferation and apoptosis.

Methods: HDM-allergic donor PBMC were cultured for 14 days with different concentrations of HDM extract (1, 10 and 100 microg/ml).