Familial hypercholesterolaemia: identification and management. Evidence reviews for case-finding, diagnosis and statin monotherapy

This guideline covers identifying and managing familial hypercholesterolaemia (FH), a specific type of high cholesterol that runs in the family, in children, young people and adults. It aims to help identify people at increased risk of coronary heart disease as a result of having FH. In November 2017, we reviewed the evidence for case finding and diagnosis, identification using cascade testing, and management using statins. We amended recommendations in sections 1.1, 1.2 and 1.3

An intestinal galactose-specific lectin mediates the binding of murine IgE to mouse intestinal epithelial cells

A number of lactose-binding lectins have recently been identified in the rat and mouse intestine, one of which corresponds to the C-terminal domain of IgE-binding proteins, originally identified in rat basophilic leukemia (RBL) cells and mouse 3T3 fibroblasts. In the present report, we describe the affinity purification of a rat intestinal lactose-specific lectin which binds murine IgE antibodies. This binding most likely occurs via the immunoglobulin carbohydrate chains, as it is inhibited by lactose. This intestinal lectin molecule is also immunologically related to the previously described IgE-binding protein (epsilon BP) isolated from RBL cells, since it is recognized by antibodies raised against recombinant epsilon BP. This intestinal form of epsilon BP has a molecular mass of 17.5 kDa, which is much lower than that of its RBL cell analogue (31 kDa). The attachment of IgE to the mouse intestinal epithelium was demonstrated by immunohistochemistry, along with the presence of a corresponding mouse intestinal epsilon BP. The carbohydrate-dependent nature of this attachment was established by demonstrating that IgE binding to mouse epithelium was specifically abolished by lactose (4 mM) and by a blood-group-A-active tetrasaccharide (0.2 mM), but not by mannose (10 mM). Finally, the association of IgE with the mouse intestinal epithelium was prevented by competition with the purified IgE-binding lectin isolated from rat intestine. Although the physiological function of this intestinal protein is still unknown, the finding that IgE binds to a lectin in the intestinal epithelium pinpoints a possible novel mechanism for the regulation of IgE-mediated disorders, such as food allergy

Galectin-3: is this member of a large family of multifunctional lectins (already) a therapeutic target?

29 p.-4 fig.-1 tab.-1 fig.supl.Introduction: The discoveries that sugars are a highly versatile platform to generate biochemical messages and that glycan-specific receptors (lectins) are a link between these signals and their bioactivity explain the interest in endogenous lectins such as galectins. Their analysis is a highly dynamic field. It is often referred to as being promising for innovative drug design.Area covered: We present a primer to the concept of the sugar code by glycan-(ga)lectin recognition, followed by a survey on galectin-3 (considering common and distinct features within this family of multifunctional proteins expressed at various cellular sites and cell types). Finally, we discuss strategies capable of blocking (ga)lectin activity, with an eye on current challenges and inherent obstacles.Expert opinion: The emerging broad profile of homeostatic and pathophysiological bioactivities stimulates further efforts to explore galectin (Gal-3) functionality, alone and then in mixtures. Like thoroughly assessing the pros and cons of blocking approaches for a multifunctional protein active at different sites, identifying a clinical situation, in which the galectin is essential in the disease process, will be critical.Peer reviewe