TY - JOUR

T1 - Circulating antibodies against leukotoxin A as marker of periodontitis grades B and C and oral infection with Aggregatibacter actinomycetemcomitans

AU - Damgaard, Christian

AU - Danielsen, Anne Katrine

AU - Enevold, Christian

AU - Reinholdt, Jesper

AU - Holmstrup, Palle

AU - Nielsen, Claus H.

AU - Massarenti, Laura

PY - 2021

Y1 - 2021

N2 - Background: The facultative bacterium Aggregatibacter actinomycetemcomitans (Aa) is strongly associated with periodontitis and is occasionally found in periodontally healthy subjects. We aimed to determine the prevalence of salivary Aa among patients with either periodontitis grade B (periodontitis-B) or grade C (periodontitis-C), periodontally healthy controls (HCs), and to determine if systemic antibodies against Aa or its virulence factor leukotoxin A (LtxA) may serve as biomarkers that reveal the oral presence of the bacterium and discriminate subjects with periodontitis-C, periodontitis-B, or no periodontitis from each other. Methods: Serum and unstimulated saliva samples were collected from patients with periodontitis-C (n = 27), patients with periodontitis-B (n = 34), and HCs (n = 28). Serum level of immunoglobulin G antibodies to fragmented whole Aa and to LtxA were quantified using a bead-based assay. Aa was identified in saliva using quantitative polymerase chain reaction (qPCR). All analyses were adjusted for age, sex, and current smoking status. Results: Aa was present in saliva from 11% of HCs, in 32% of patients with periodontitis-B (P = 0.04 versus HCs), and in 37% of patients with periodontitis-C (P = 0.02 versus HCs). Serum antibodies to fragments of Aa associated significantly with periodontitis-C (P = 0.03), while serum anti-LtxA antibodies associated with both periodontitis-B and periodontitis-C (P = 0.002 and P = 9×10−4, respectively). Moreover, a significant association between serum anti-LtxA antibodies and Aa count in saliva was observed (P = 0.001). On the basis of serum anti-LtxA antibody levels, patients with periodontitis could be discriminated from HCs (AUC = 0.74 in ROC curve-analysis, P = 0.0003), and carriers of Aa could be discriminated from non-carriers (AUC = 0.78, P <0.0001). Conclusions: Aa is highly prevalent in saliva of patients with periodontitis-B or periodontitis-C. Systemic immunoglobulin G antibodies against LtxA distinguish patients with periodontitis, regardless of grade, from HCs, while their quantity reflects the concurrent bacterial burden in the oral cavity.

AB - Background: The facultative bacterium Aggregatibacter actinomycetemcomitans (Aa) is strongly associated with periodontitis and is occasionally found in periodontally healthy subjects. We aimed to determine the prevalence of salivary Aa among patients with either periodontitis grade B (periodontitis-B) or grade C (periodontitis-C), periodontally healthy controls (HCs), and to determine if systemic antibodies against Aa or its virulence factor leukotoxin A (LtxA) may serve as biomarkers that reveal the oral presence of the bacterium and discriminate subjects with periodontitis-C, periodontitis-B, or no periodontitis from each other. Methods: Serum and unstimulated saliva samples were collected from patients with periodontitis-C (n = 27), patients with periodontitis-B (n = 34), and HCs (n = 28). Serum level of immunoglobulin G antibodies to fragmented whole Aa and to LtxA were quantified using a bead-based assay. Aa was identified in saliva using quantitative polymerase chain reaction (qPCR). All analyses were adjusted for age, sex, and current smoking status. Results: Aa was present in saliva from 11% of HCs, in 32% of patients with periodontitis-B (P = 0.04 versus HCs), and in 37% of patients with periodontitis-C (P = 0.02 versus HCs). Serum antibodies to fragments of Aa associated significantly with periodontitis-C (P = 0.03), while serum anti-LtxA antibodies associated with both periodontitis-B and periodontitis-C (P = 0.002 and P = 9×10−4, respectively). Moreover, a significant association between serum anti-LtxA antibodies and Aa count in saliva was observed (P = 0.001). On the basis of serum anti-LtxA antibody levels, patients with periodontitis could be discriminated from HCs (AUC = 0.74 in ROC curve-analysis, P = 0.0003), and carriers of Aa could be discriminated from non-carriers (AUC = 0.78, P <0.0001). Conclusions: Aa is highly prevalent in saliva of patients with periodontitis-B or periodontitis-C. Systemic immunoglobulin G antibodies against LtxA distinguish patients with periodontitis, regardless of grade, from HCs, while their quantity reflects the concurrent bacterial burden in the oral cavity.

KW - Aggregatibacter actinomycetemcomitans

KW - antibodies

KW - periodontitis

KW - saliva

KW - serum

U2 - 10.1002/JPER.20-0895

DO - 10.1002/JPER.20-0895

M3 - Journal article

C2 - 33749825

AN - SCOPUS:85104391362

VL - 92

SP - 1795

EP - 1804

JO - Journal of Periodontology

JF - Journal of Periodontology

SN - 0022-3492

IS - 12

ER -