Design of TOLERANT: phase I/II safety assessment of intranodal administration of HSP70/mB29a self-peptide antigen-loaded autologous tolerogenic dendritic cells in patients with rheumatoid arthritis.

Introduction: In rheumatoid arthritis (RA), immunosuppressive therapies may achieve symptomatic relief, but do not induce long-term, drug-free remission. Meanwhile, the lifelong use of immunosuppressive drugs confers increased risk for malignancy and infections. As such, there is an unmet need for novel treatments that selectively target the pathogenic immune response in RA by inducing tolerance to autoantigens.

Heat Shock Proteins Can Be Surrogate Autoantigens for Induction of Antigen Specific Therapeutic Tolerance in Rheumatoid Arthritis.

Technologies that enable induction of therapeutic tolerance may revolutionize the treatment of autoimmune diseases by their supposed potential to induce drug-free and lasting disease remission. In combination with diagnostic tests that screen for individuals at risk, these approaches may offer chances to halt disease before serious damage in the tissues can occur. In fact, for healthy individuals at risk, this could lead to a preventive form of vaccination.

Multimodality imaging for real-time image-guided left ventricular lead placement during cardiac resynchronization therapy implantations.

This study was performed to evaluate the feasibility of intra-procedural visualization of optimal pacing sites and image-guided left ventricular (LV) lead placement in cardiac resynchronization therapy (CRT). In fifteen patients (10 males, 68 ± 11 years, 7 with ischemic cardiomyopathy and ejection fraction of 26 ± 5%), optimal pacing sites were identified pre-procedurally using cardiac imaging. Cardiac magnetic resonance (CMR) derived scar and dyssynchrony maps were created for all patients.

The Immunomodulatory Potential of tolDCs Loaded with Heat Shock Proteins.

Disease suppressive T cell regulation may depend on cognate interactions of regulatory T cells with self-antigens that are abundantly expressed in the inflamed tissues. Heat shock proteins (HSPs) are by their nature upregulated in stressed cells and therefore abundantly present as potential targets for such regulation. HSP immunizations have led to inhibition of experimentally induced inflammatory conditions in various models.

The inhibition of mast cell activation by neutrophil lactoferrin: uptake by mast cells and interaction with tryptase, chymase and cathepsin G.

Inhibitors of mast cell tryptase and chymase can be effective as mast cell stabilising compounds. Lactoferrin has been reported to inhibit tryptase activity, but its actions on other serine proteases of mast cells and its potential to alter mast cell function are not known. We have examined the ability of lactoferrin to inhibit mast cell tryptase, chymase and cathepsin G, and investigated its potential to modulate the activation of human mast cells.