Immunogenicity of recombinant human interferon beta interacting with particles of glass, metal, and polystyrene

Aggregates play a major role in the immunogenicity of recombinant human interferon beta (rhIFNβ), a protein used to treat multiple sclerosis. A possible cause of aggregation is interaction between therapeutic protein and surfaces encountered during processing, storage, and administration. Moreover, proteins may adsorb to particles shed from these surfaces. In this work, we studied the immunogenicity of recombinant human interferon beta-1a (rhIFNβ-1a) interacting with glass microparticles, stainless steel microparticles, and polystyrene nanoparticles. At physiological pH, rhIFNβ-1a readily adsorbed to the particles, while the degree of adsorption was influenced by the ionic strength of the phosphate buffer. Front-face fluorescence showed that the tertiary structure of rhIFNβ-1a slightly changed upon adsorption to glass. The interaction with stainless steel microparticles resulted in increased levels of aggregates in the free protein fraction. Furthermore, protein adsorbed to stainless steel microparticles was more difficult to desorb than protein adsorbed to glass. Incubation with stainless steel considerably enhanced the immunogenicity of rhIFNβ-1a in transgenic mice immune tolerant for human interferon beta. The protein fraction adsorbed on stainless steel particles was responsible for this. In conclusion, rhIFNβ-1a adsorbs to common hydrophilic surface materials, possibly increasing the immunogenicity of the protein

Stakeholder values and platform wars: smart meters in the Netherlands

The interconnected nature of the different components of smart grids is a prime example of complexity in technological systems. Developing such systems is highly dependent on the wishes and needs of end-users and other stakeholders. We argue that stakeholder values should be taken into consideration during the design and standardisation of complex infrastructures, and illustrate this with a case of smart meters and home energy management systems. We base our argument on the literature in the technology management fields, particularly those strands related to standardisation. We conduct a case study of the acceptance of smart meters (standards) in the Netherlands, based on stakeholder interviews. We use q-methodology to analyse the most salient values in this case. The Dutch smart meter case arguably demonstrates that a lack of consideration for stakeholder values led to the postponed roll-out of smart meters in the Netherlands. By not addressing privacy issues, economic advantages, and the need for informed consent, the roll-out of smart meters was delayed for several years. This lead to a more gradual approach and increased stakeholder involvement. This case may serve as an example for other European countries who also face public concern regarding the impact of advanced metering infrastructures.Economics of Technology and InnovationValues Technology and InnovationEnergy & Industr

A HIGH FREQUENCY OF N-GLYCANS IN THE ACPA-IGG VARIABLE DOMAIN MODULATES REACTIVITY TO CITRULLINATED ANTIGENS

Pathophysiology and treatment of rheumatic disease