Tannerella forsythia (Tf) is a Gram-negative anaerobe implicated in the development of periodontal disease. Bacterial surface protein A (BspA) is a surface-expressed and -secreted protein that is recognized as an important virulence factor of Tf. This study was undertaken to determine whether Tf BspA induces an antibody response in periodontal disease. We hypothesized that serum immunoglobulin (Ig)G antibody levels against BspA correlate with the disease of patients.Sera were obtained from 100 patients with cardiac disorders and periodontal disease and 73 patients who experienced myocardial infarction but were periodontally healthy. Sera samples were assayed for anti-BspA antibody (total IgG and IgG subtypes) by enzyme-linked immunosorbent assay (ELISA). Antibody levels were measured in ELISA units by using an arbitrary patient as a standard.A negative correlation was found with BspA-specific total IgG antibody titers and the severity of disease measured as the clinical attachment level (CAL) when healthy and diseased groups were analyzed separately (healthy group: [-0.23, correlation value] Student's t value [73 degrees of freedom] = 1.99; P = 0.05; diseased group: [-0.21] t [100 degrees of freedom] = 2.12; P = 0.03]). However, there was a positive correlation ([0.18 correlation value] Student's t value [173 degrees of freedom] = 2.39; P = 0.017) when healthy and diseased groups were combined. A strong positive correlation ([0.338 correlation value] Student's t value [173 degrees of freedom] = 4.69; P <0.0001) between the BspA-specific IgG titers and periodontal probing depth was observed when healthy and disease groups were combined.Data demonstrated that antibodies to Tf BspA were elicited in patients with periodontal disease, and antibody levels were associated with the disease severity. Furthermore, data suggested that anti-BspA IgG might have a protective function in periodontal disease by minimizing the loss of tooth attachment tissue.