Nonenzymatic Glycosylation of Immunoglobulin G Impairs Complement Fixation

Abstract

Transient hyperglycemia in patients receiving total parenteral nutrition may be associated with impaired immune function. The effects of short-term hyperglycemia on one aspect of antimicrobial immune function, ie, the ability of IgG to fix complement, were investigated. Aliquots of antihuman albumin, anti-horse ferritin, and anti-alkaline phosphatase were incubated for 0, 8, 16, 24, 48, and 96 hr with either 0 or 240 mg of glucose per deciliter of buffer. All samples were analyzed for the degree of glycation using a thiobarbituric acid assay, and for complement fixation ability using a microcomplement fixation assay. Significant increases in glycation over control samples were observed after only 16 hr (31 us 15 mmol 5-hydroxymethylfurfural/mol IgG, p < 0.01). Complement fixation was significantly altered after 48 hr of incubation (76 ± 5% vs 90 ± 8% total serum complement fixed by albumin/antialbumin complex, p < 0.03) when four of the 84 (4.7%) IgG lysine residues were glycated. It is demonstrated that a significant reduction in complement fixation by immunoglobulin occurs with elevated glucose concentrations and that this may play a clinically significant role in transiently hyperglycemic patients. (Journal of Parenteral and Enteral Nutrition 15:60-64, 1991)