Point-of-Use Mixing of Influenza H5N1 Vaccine and MF59 Adjuvant for Pandemic Vaccination Preparedness: Antibody Responses and Safety. A Phase 1 Clinical Trial.

Background: Avian influenza A/H5N1 has threatened human health for nearly 2 decades. Avian influenza A vaccine without adjuvant is poorly immunogenic. A flexible rapid tactic for mass vaccination will be needed if a pandemic occurs.

Discussion: 'Factor V Leiden mutation' by Kjellberg et al.

In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research.

Is there a role of autoimmunity in implantation failure after in-vitro fertilization?

Purpose Of Review: The process of implantation involves the interaction of the human blastocyst and the uterine epithelium. Several autoimmune factors have been implicated to have an influence on implantation failure.

Recent Findings: Recent studies have investigated the role of autoimmune factors in implantation in women undergoing in-vitro fertilization.

Editing and escape from editing in anti-DNA B cells.

Tolerance to dsDNA is achieved through editing of Ig receptors that react with dsDNA. Nevertheless, some B cells with anti-dsDNA receptors escape editing and migrate to the spleen. Certain anti-dsDNA B cells that are recovered as hybridomas from the spleens of anti-dsDNA H chain transgenic mice also bind an additional, Golgi-associated antigen.

Murine lupus autoantibodies identify distinct subsets of apoptotic bodies.

The specific modification of autoantigens and their redistribution into blebs at the surface of apoptotic cells contribute to the induction of autoimmune responses. Blebs containing fragments of the apoptotic nucleus separate from the remainder of the cell to form membrane-bound sub-cellular particles (SCPs), otherwise known as apoptotic bodies. To determine whether apoptotic bodies containing nuclear antigens represent a defined subset of SCPs, we examined the heterogeneity of particles generated by Jurkat cells following synchronization of the cell cycle by serum withdrawal and inhibition of topoisomerase I by camptothecin.

Apoptosis, subcellular particles, and autoimmunity.

Firm evidence links the process of apoptosis to the induction of autoimmune disease. However, questions remain regarding the precise interactions of dying cells with the immune system. Genetic analyses indicate that deficiencies in serum proteins or receptors that mediate clearance of apoptotic cells increase the risk of autoimmunity.

Blebs and apoptotic bodies are B cell autoantigens.

Mounting evidence suggests that systemic lupus erythematosus autoantigens are derived from apoptotic cells. To characterize the potential interactions between apoptotic cells and B cells, the D56R/S76R variant of 3H9, a murine autoantibody that binds to DNA, chromatin, and anionic phospholipids, was compared with DNA4/1, a human anti-DNA autoantibody. Flow cytometry revealed that only D56R/S76R bound to Jurkat cells treated with either of three distinct proapoptotic stimuli, Ab binding was dependent on caspase activity, and immunoreactivity developed subsequent to annexin V binding.