Molecular mimicry of Aggregatibacter actinomycetemcomitans with β2 glycoprotein I

Abstract

beta2-Glycoprotein I (beta 2GPI) is important in the suppression of coagulation, and antibodies against TLRVYK peptides on the beta 2GPI molecule are related to thrombosis. According to the Swiss-Prot database, Aggregatibacter actinomycetemcomitans leukotoxin c has sequences (SIRVYK) that are homologous to the TLRVYK peptides. The aim of this study was to investigate the effects of A. actinomycetemcomitans infection on the antibody response against SIRVYK peptides in patients with periodontitis. Serum immunoglobulin G (IgG) antibody and IgG subclass antibody titers against SIRVYK or TLRVYK peptides were measured by enzyme-linked immunosorbent assay in 46 patients with aggressive periodontitis (eight with localized disease, 38 with generalized disease), 28 patients with chronic periodontitis, and 20 periodontally healthy subjects. The presence of A. actinomycetemcomitans in plaque and saliva samples was determined using polymerase chain reaction. The level of anti-SIRVYK antibodies was significantly higher in patients who were A. actinomycetemcomitans-positive than in A. actinomycetemcomitans-negative patients (P < 0.05) in the chronic periodontitis group. A similar trend was found in the antibody response to TLRVYK peptide; however, no statistically significant difference was seen between A. actinomycetemcomitans-positive and -negative patients. The A. actinomycetemcomitans-positive patients displayed significantly higher levels of anti-SIRVYK IgG2 and IgG3 antibodies than A. actinomycetemcomitans-negative patients (P < 0.05 and P < 0.05, respectively). The level of IgG2 was highest among the four IgG subclasses and it predominantly increased in patients who were A. actinomycetemcomitans-positive. Anti-TLRVYK antibody levels were significantly correlated with anti-SIRVYK IgG antibody levels. The results suggest that A. actinomycetemcomitans infection may elicit anti-SIRVYK IgG antibodies and modify the anti-TLRVYK antibody response in patients with periodontitis by molecular mimicry with beta2GPI.