CNS vasculitis in a patient with MS on daclizumab monotherapy.

Objective: To report the development of CNS vasculitis in a patient with multiple sclerosis (MS) treated with daclizumab.

Methods: This report includes clinical, MRI, immunologic, and pathology data and CSF analysis.

Results: After completing a phase II daclizumab monotherapy study with an optimal response as evidenced by significant decrease in MRI disease activity and stable clinical examinations, the patient elected to continue daclizumab therapy outside of NIH study.

A role for interleukin-2 trans-presentation in dendritic cell-mediated T cell activation in humans, as revealed by daclizumab therapy.

Although previous studies have described CD25 expression and production of interleukin-2 (IL-2) by mature dendritic cells (mDCs), it remains unclear how these molecules participate in the activation of T cells. In search of the mechanisms by which daclizumab, a humanized monoclonal antibody against CD25, inhibits brain inflammation in multiple sclerosis, we observed that although the drug has limited effects on polyclonal T cell activation, it potently inhibits activation of antigen-specific T cells by mDCs. We show that mDCs (and antigen-experienced T cells) secrete IL-2 toward the mDC-T cell interface in an antigen-specific manner, and mDCs 'lend' their CD25 to primed T cells in trans to facilitate early high-affinity IL-2 signaling, which is crucial for subsequent T cell expansion and development of antigen-specific effectors.

Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue.

Obesity elicits an immune response characterized by myeloid cell recruitment to key metabolic organs, including adipose tissue. However, the response of immune cells to nonpathologic metabolic stimuli has been less well studied, and the factors that regulate the metabolic-dependent accumulation of immune cells are incompletely understood. Here we characterized the response of adipose tissue macrophages (ATMs) to weight loss and fasting in mice and identified a role for lipolysis in ATM recruitment and accumulation.

An IL-2 paradox: blocking CD25 on T cells induces IL-2-driven activation of CD56(bright) NK cells.

Daclizumab (Dac), an Ab against the IL-2R alpha-chain, inhibits brain inflammation in patients with multiple sclerosis, while expanding CD56(bright) immunoregulatory NK cells in vivo. We hypothesized that this unexpected expansion is paradoxically IL-2 driven; caused by the increased availability of T cell-derived IL-2 for NK cell signaling. To this end, we performed ex vivo functional analyses of CD56(bright) NK cells and T cells from patients in clinical trials with Dac.

Unusual presentation of hereditary neuropathy with liability to pressure palsies.

Background: Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant painless peripheral neuropathy characterized by episodes of repeated focal pressure neuropathies at sites of entrapment/compression, with a considerable variability in the clinical course. Electrodiagnostic and genetic testing are important in the diagnostic evaluation of these patients.

Case Presentation: We report an unusual HNPP phenotype, five compression neuropathies in four nerves in a patient with bilateral hand numbness.