title: 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 anti-human 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 vs 15 mmol 5-hydroxymethylfurfural/mol IgG, p less than 0.01). Complement fixation was significantly altered after 48 hr of incubation (76 +/- 5% vs 90 +/- 8% total serum complement fixed by albumin/anti-albumin complex, p less than 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.
authors.affiliation: Department of Surgery, University of Texas Medical School, Houston, Texas 77030.
authors.forename: P J
authors.initials: PJ
authors.lastname: Hennessey
authors.forename: C T
authors.initials: CT
authors.lastname: Black
authors.forename: R J
authors.initials: RJ
authors.lastname: Andrassy
mesh_terms: D000469:Alkaline Phosphatase / Q000276:immunology; D000818:Animals; D003168:Complement Fixation Tests; D005293:Ferritins / Q000276:immunology; D006031:Glycosylation; D006801:Humans; D006943:Hyperglycemia / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D012709:Serum Albumin / Q000276:immunology
chemical_list: D007106:Immune Sera; D007074:Immunoglobulin G; D012709:Serum Albumin; D005293:Ferritins; D000469:Alkaline Phosphatase