Prevalence of systemic immunoreactivity to Aggregatibacter actinomycetemcomitans leukotoxin in relation to the incidence of myocardial infarction

Abstract

BackgroundChronic infections and associated inflammatory markers are suggested risk factors for cardiovascular disease (CVD). The proinflammatory cytokine, interleukin (IL)-1β, is suggested to play a role in the regulation of local inflammatory responses in both CVD and periodontitis. The leukotoxin from the periodontal pathogen Aggregatibacter actinomycetemcomitans has recently been shown to cause abundant secretion of IL-1β from macrophages. The aim of the present study was to compare the prevalence of systemic immunoreactivity to A. actinomycetemcomitans leukotoxin in myocardial infarction (MI) cases (n = 532) and matched controls (n = 1,000) in a population-based case and referents study in northern Sweden.MethodsCapacity to neutralize A. actinomycetemcomitans leukotoxin was analyzed in a bioassay with leukocytes, purified leukotoxin, and plasma. Plasma samples that inhibited lactate-dehydrogenase release from leukotoxin-lysed cells by ≥50% were classified as positive.ResultsNeutralizing capacity against A. actinomycetemcomitans leukotoxin was detected in 53.3% of the plasma samples. The ability to neutralize leukotoxin was correlated to increasing age in men (n = 1,082) but not in women (n = 450). There was no correlation between presence of systemic leukotoxin-neutralization capacity and the incidence of MI, except for women (n = 146). Women with a low neutralizing capacity had a significantly higher incidence of MI than those who had a high neutralizing capacity.ConclusionSystemic immunoreactivity against A. actinomycetemcomitans leukotoxin was found at a high prevalence in the analyzed population of adults from northern Sweden. The results from the present study do not support the hypothesis that systemic leukotoxin-neutralizing capacity can decrease the risk for MI.

Systemic Aggregatibacter actinomycetemcomitans Leukotoxin‐Neutralizing Antibodies in Periodontitis

“…The present study found slightly but significantly increased presence of Ltx‐neutralizing antibodies in patients versus controls. Significant correlation was found between presence of strong Ltx immunoreactivity with increasing age in examined patients and controls, which is in line with previous findings 13,17,34,35 . These findings are difficult to explain when the colonization pattern of A. actinomycetemcomitans is believed to be strictly vertical with a transmission window that closes early in life 1 .…”

“…A. actinomycetemcomitans is also considered to be an early colonizer owing to its ability to colonize buccal epithelial cells, which could act as reservoir for the bacterium 7 , 36 . However, transmission between adults may occur randomly, contributing to increased prevalence of Ltx antibodies related to higher age, as seen in previous studies 13,17,34,35 and in the present study.…”

Aggregatibacter actinomycetemcomitans Leukotoxin: A Powerful Tool with Capacity to Cause Imbalance in the Host Inflammatory Response

“…However, the strong correlation between the presence of highly leukotoxic (JP2-clone) A. actinomycetemcomitans and development of attachment loss in adolescents indicates an important role of LtxA in the pathogenesis of aggressive periodontitis [ 3 ]. The treatment strategies of periodontal disease are today focused on the elimination of the bacteria in the subgingval biofilm by mechanical techniques or with antibacterial agents [ 87 ]. Therapeutic agents that target the cellular and molecular inflammatory host response might be a future treatment alternative for periodontal disease.…”

Virulence Mechanisms of Leukotoxin from Aggregatibacter actinomycetemcomitans

“…It has also been shown that systemic leukotoxin neutralization is correlated to the presence of this bacterium in the subgingival plaque (Källestål et al, 1991;Sjödin et al, 1995;Carlsson et al, 2006). The prevalence of systemic leukotoxin antibodies has been shown to be present in >50% in samples from adults and without significant differences in relation to periodontitis (Brage et al, 2011;Johansson et al, 2011). Interestingly, systemic leukotoxin neutralization correlates to decreased risk of the incidence of stroke in woman .…”