Longitudinal human serum antibody responses to outer membrane antigens of Actinobacillus actinomycetemcomitans

Abstract

We hypothesize that serum antibody responses to antigens of a periodontopathogen would vary temporally and that the specificity of these host antibodies would relate to infection and disease activity. To test the hypothesis, we obtained between 6 and 13 serum samples from Actinobacillus actinomycetemcomitans (Aa)-positive (serological and microbiological) periodontitis patients at time points between 18 and 42 months into the study, and evaluated specific antibody responses to outer membrane antigens (OMA) of Aa strain Y4. Sera from these patients detected 22 different OMA. Early-onset (EOP; n=7) and adult (AP; n=11) periodontitis patients responded to 35% and 41% of the OMA, respectively. 2 of 9 sera from healthy subjects detected no antigens and 7/9 sera detected 7% of the OMA (p<0.0001 versus EOP and AP). The frequency of antibody responses to the 17 kDa antigen were similar between diseased, infected patients and the uninfected, normal subjects, suggesting that it may be stimulated as a cross-reactive antigen. Antibody to the 28, 38, and 90 kDa antigens were significantly more common in diseased patients (>90%) versus normal subjects (p<0.01, p<0.002, and p<0.002, respectively) and were unique among diseased, infected patients, which may be indicative of infections with Aa. A 65 kDa antigen showed an increased frequency of reaction in the AP versus the EOP (p=0.01) patients, which exemplified a potential distinction in response to Aa between adult and early-onset disease classifications. Seventeen of 22 OMA could be detected in every sample from at least one patient. Longitudinal samples from seropositive EOP and AP reacted 80-100% of the time with the 17, 28, and 100 kDa antigens. Finally, five antigens of 15, 38, 58, 65, and 79 kDa were detected in 33-83% of the seropositive patients; however, antibody to these OMA reacted variably at different sampling points, suggesting some antigenic response diversity over time.

Serum antibodies to periodontal pathogens are a risk factor for Alzheimer's disease

“…Therefore these elevations cannot be attributed to secondary effects of the AD disease process, such as poor nutrition or other dementia-related neglect. While it could be suggested that the antibody to these oral pathogens may have been cross-reactive with antigens from other sources, the literature is replete with studies supporting the specificity of these antibodies for oral infections [20–21, 43–46], and that successful treatment and maintenance of periodontitis significantly lowers these antibody levels [47]. Comparison of these antibody levels to those described in numerous populations show levels in the AD and MCI subjects in the current study to be similar to chronic periodontitis patients [45–49].…”

Proteomic and immunoproteomic analysis of Aggregatibacter actinomycetemcomitans JP2 clone strain HK1651

“…Previous studies have demonstrated serum antibody responses to some outer membrane proteins of A. actinomycetemcomitans [11,12]. Principal putative virulence determinants of A. actinomycetemcomitans include the leukotoxin, a cytolethal toxin, the cell wall lipopolysaccharide, and fimbria [3,[13][14][15][16].…”

“…Principal putative virulence determinants of A. actinomycetemcomitans include the leukotoxin, a cytolethal toxin, the cell wall lipopolysaccharide, and fimbria [3,[13][14][15][16]. Moreover, several outer membrane proteins have been recorded as immunogenic at the molecular level, such as RcpA, a 43-kDa protein, which is similar to precursor protein D of the general secretion pathway of Gram-negative bacteria and genetically related to fimbria-associated proteins [17], AaPAL, a 17 kDa protein, which has been identified as a highly immunoreactive peptidoglycan-associated lipoprotein [12], Omp34, a protein belonging to the OmpA family [18][19][20], and the heat-modifiable Omp16 [11,21]. Studies using in vivo induced antigen technology (IVIAT) [22] have the potential to identify large numbers of immunogenic antigens.…”

Effects of Age and Oral Disease on Systemic Inflammatory and Immune Parameters in Nonhuman Primates

“…Increased levels of acute-phase proteins have been identified in adult periodontitis patients and appear to reflect both the infection and the acute and chronic inflammation that exists in the periodontium (18,39,55). At the same time, it is clear that a serum antibody response to these localized infections exists and that it results from specific elicitation of antibody to an infecting microorganism (19,24,40,41,46,79).Periodontal disease has been effectively used as a model of host-bacterium interactions, inflammation, and chronic inflammatory diseases, particularly for the ability to longitudinally describe bacterial and host factors in the oral cavity and to correlate changes in these factors with pathological changes in …”