Articles
were screened using MEDLINE (n = 566), EMBASE (n = 201), and the Cochrane Library (n = 1). Two independent reviewers assessed articles PXD101 molecular weight for inclusion under the overarching purposes of the review by using the Standards for Reporting of Diagnostic Accuracy (STARD) tool, and the quality of the studies were graded using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. The electronic literature search retrieved 777 references (after duplicates were removed). A total of 32 studies were chosen for inclusion from the results of the search and review of bibliographical references. Using the STARD tool, seven studies were of excellent quality of reporting, and using the selleck compound QUADAS-2 tool, 10 studies were judged to be of adequate quality. There is ‘fair’ evidence to recommend MRI as an accurate test for detecting evidence of haemophilic arthropathy and the use of second or third generation MRI scales for assessing haemophilic arthropathy. However, there is no evidence that screening of early intra-articular
soft tissue bleed with MRI improves the functional status of joints over time. “
“Summary. The mechanism of action of antibodies inhibiting partially factor VIII (FVIII) activity (type II inhibitor) is still poorly understood. We produced an unusual type II monoclonal antibody, called LE2E9, derived from a patient with mild haemophilia A. The antibody displayed several unexpected structural and functional properties such as glycosylation in the variable region, binding to the FVIII C1 domain, inhibition of maximum 80–90%
FVIII activity when in excess over FVIII, and prevention of FVIII binding to von Willebrand factor (VWF). Those unusual characteristics of the antibody prompted multidisciplinary studies to determine its mechanism of action and the role of the FVIII C1 domain. Enzymatic deglycosylation and site-directed mutagenesis indicated that the oligosaccharides do not determine the affinity of the antibody next but enhanced its FVIII neutralizing activity. Modification of glycosylation in the variable region of antibodies therefore contributes to the diversity of FVIII type II inhibition and provides a novel strategy with which to modulate the functional activity of antibodies. Investigation of the FVIII C1 domain function led to identification of mutations located in that domain and impairing FVIII binding to VWF as a common cause of mild/moderate haemophilia A. Finally, the cloning of human monoclonal antibodies inhibiting partially FVIII activity opened the way to evaluate such antibodies as a novel type of anticoagulant drug.