The author is grateful to Professors Sven Björkman, Peter Collins and Kathelijn Fischer for their helpful suggestions during BGJ398 preparation of this manuscript. The author stated that he had no interests which might be perceived as posing a conflict or bias. “
“The administration of therapeutic factor VIII (FVIII) to treat or
prevent haemorrhages in haemophilia A patients results, in up to 30% of the cases, in the development of inhibitory anti-FVIII antibodies. Much debate has taken place on the relevance of the nature of the FVIII product as a risk factor for inhibitor development. Thus, the plasma-derived vs. recombinant origin, the second vs. third generation of the product, or the presence of the B domain have been controversially evoked. A few years ago, Refacto®
AF, a third-generation recombinant B domain-deleted FVIII was marketed. The aim of this study was to compare the immunogenicity of Refacto® AF to that of two recombinant full-length FVIII products: Helixate® and Advate®. For the three recombinant FVIII products, we compared the binding to the mannose-sensitive endocytic receptor CD206, the dose-dependent endocytosis by immature monocyte-derived dendritic cells (DCs), the activation by FVIII-loaded DCs of a FVIII-specific HLA-DRB1*0101-restricted Bortezomib price mouse T-cell hybridoma and the induction of inhibitory anti-FVIII IgG in FVIII-deficient Janus kinase (JAK) mice. At elevated FVIII concentrations, Refacto® AF was less endocytosed than full-length recombinant products. At lower concentrations, however, Refacto® AF was endocytosed by DCs and activated T cells as well
as Helixate® and Advate®. The levels of inhibitory anti-FVIII IgG induced by Refacto® AF in FVIII-deficient mice were lower or equal to that induced by Helixate® and Advate® respectively. The predicted immunogenicity of Refacto® AF is identical to or lower than that of the two recombinant full-length FVIII products available on the French market. “
“Summary. Many diseases and injuries can impair joint mobility. Normal reference values are needed to determine extent of impairment to assess and monitor joint motion. There is very little published data describing normal joint range of motion (ROM) for healthy men and women across a wide span of ages. We enrolled male and female subjects aged between 2 and 69 years who were free from conditions that could potentially limit joint mobility for the study. Nine licensed physical therapists used universal goniometers to determine passive joint motion bilaterally of elbow flexion, extension, supination and pronation, shoulder flexion, hip flexion and extension, knee flexion and extension, and ankle dorsiflexion and plantarflexion. Descriptive statistics were calculated for male and female subjects in four age groups: 2–8, 9–19, 20–44 and 45–69 years.