title: Glycation of CD59 impairs complement regulation on erythrocytes from diabetic subjects.
abstract: Type 1 diabetes is associated with anaemia. Although the underlying mechanisms remain unclear, the accompanying reticulocytosis implies that erythrocyte lifespan in the circulation is shortened. Among the factors that permit prolonged survival of erythrocytes are the membrane complement regulators. In conditions such as paroxysmal nocturnal haemoglobinuria, where erythrocyte expression of these regulators is reduced, erythrocyte survival is compromised and anaemia follows. Recent in vitro evidence indicates that one of the key membrane complement regulators, CD59, is inactivated by glycation in the presence of high concentrations of glucose or other glycating sugars. To ascertain whether glycation-induced inactivation of CD59 occurrs in vivo we examined CD59 surface expression and function on erythrocytes from a cohort with poorly controlled type 1 diabetes (hyperglycaemic) and from matched normoglycaemic controls. Although expression of CD59, assessed using polyclonal anti-CD59 antiserum, was similar in the two groups, erythrocytes from hyperglycaemic individuals were more susceptible to lysis by complement, entirely as a result of the loss of functional CD59. These data implicate glycation-induced inactivation of CD59 as a factor contributing to anaemia in type 1 diabetes.
authors.affiliation: Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Davies
authors.forename: Claire L
authors.initials: CL
authors.lastname: Harris
authors.forename: B Paul
authors.initials: BP
authors.lastname: Morgan
mesh_terms: D000368:Aged; D018957:CD59 Antigens / Q000378:metabolism*; D003171:Complement Pathway, Classical; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D006461:Hemolysis; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D018957:CD59 Antigens