title: Effect of nonenzymatic glycosylation on the titers of circulating autoantibodies in pemphigus and pemphigoid.
abstract: Hyperglycemia is observed in some patients with autoimmune bullous diseases complicated by diabetes mellitus or treated with systemic corticosteroids. High concentrations of glucose can react with various proteins and change their structural and functional properties. We previously reported that nonenzymatic glycosylation of antibody can impair antigen-antibody binding. We ascertained whether glycosylation of autoantibody decreases the autoantibody titer by examining 30 sera from patients with pemphigus and pemphigoid. Nonenzymatic glycosylation in the physiological range was induced by incubation of sera with 1650 mM D-glucose at 4 degrees C for 7 days. The titers of sera were determined by indirect immunofluorescence (IIF). In all cases, the immunofluorescence intensity of glycosylated sera was weaker than that of nonglycosylated sera. Glycosylated sera showed a lower antibody titer by 1 doubling dilution in 18 out of 30 cases, compared with nonglycosylated sera. The ten BP patients' sera were also analyzed by immunoblotting for reactivity with the BP180-GST fusion proteins, S delta 1 and 4575. All BP sera reacted with S delta 1, and 5 out of 10 BP sera reacted with both S delta 1 and 4575. In all the sera that reacted only with S delta 1, the glycosylated sera showed a 1 doubling dilution decrease in autoantibody titer. Interestingly, in 4 out of 5 sera that reacted with both S delta 1 and 4575, there were no differences in the antibody titer between glycosylated and nonglycosylated sera. These results indicate the possibility of a false decrease in autoantibody titers of sera from patients with autoimmune bullous diseases complicated with hyperglycemia. Although the false decrease in titers of autoantibodies induced by nonenzymatic glycosylation is not dramatic, it must be considered in order not to underestimate the disease activity of pemphigus in such cases.
authors.affiliation: Department of Dermatology, Nara Medical University, Kashihara, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nakagawa
authors.forename: N
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Yamashina
authors.forename: C
authors.initials: C
authors.lastname: Nakatani
authors.forename: T
authors.initials: T
authors.lastname: Muramatsu
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: T
authors.initials: T
authors.lastname: Shirai
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D019084:Fluorescent Antibody Technique, Indirect; D006031:Glycosylation; D006801:Humans; D010391:Pemphigoid, Bullous / Q000097:blood / Q000276:immunology*; D010392:Pemphigus / Q000097:blood / Q000276:immunology*; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies