Complement split product C3c in saliva as biomarker for periodontitis and response to periodontal treatment

Maria Anastasia Grande, Daniel Belstrøm, Christian Damgaard, Palle Holmstrup, Sai Sindhu Thangaraj, Claus Henrik Nielsen, Yaseelan Palarasah, Maria Anastasia Grande, Daniel Belstrøm, Christian Damgaard, Palle Holmstrup, Sai Sindhu Thangaraj, Claus Henrik Nielsen, Yaseelan Palarasah

Abstract

Background and objective: The complement system is engaged in inflammatory reactions both in the periodontal pockets and in the periodontium itself, where it can mediate tissue destruction. The aim of this study was, first, to compare salivary levels of the total complement system protein C3 and its split product, fluid-phase C3c in patients with periodontitis and periodontally healthy controls. Next, to determine if C3 and C3c levels had biomarker potential in diagnosing and monitoring periodontitis and its treatment. We hypothesized that salivary levels of total C3 and the split product C3c associated with the severity of periodontitis and reflected decreased inflammatory activity after periodontal treatment.

Methods: At baseline, stimulated saliva samples were collected from patients with periodontitis (n = 18) and periodontally healthy controls (n = 15). Subsequently, non-surgical periodontal treatment was performed in the patients, and saliva sampling from patients was repeated two-, six-, and twelve weeks post-treatment (NCT02913248 at clinicaltrials.gov). The patients were grouped as good and poor responders to treatment according to the achieved reduction in bleeding on probing (BOP). Salivary levels of C3 and C3c were quantified using sandwich ELISA.

Results: Patients with periodontitis had higher baseline levels of both total C3 and the split product C3c in saliva than did periodontally healthy controls (P < .0001). Receiver operating curve (ROC) analyses discriminated patients with periodontitis from controls based on both C3 (AUC (area under curve) = 0.91, P < .001) and C3c levels (AUC = 0.84, P < .001) in saliva. Periodontal treatment improved all clinical parameters (P < .01). Good responders (n = 10) had lower baseline levels of C3c than poor responders (n = 8), (P < .05), and baseline levels of C3c discriminated between good and poor responders (AUC = 0.80, P < .05).

Conclusion: In conclusion, patients with periodontitis had higher salivary levels of C3c, and the C3c levels were predictive of reductions in BOP, that is, the poor responders. This suggests that salivary C3c levels possess potential to serve as a biomarker predicting the clinical response to non-surgical periodontal treatment.

Keywords: complement component 3; intervention; periodontitis; saliva.

Conflict of interest statement

All authors declare no conflict of interest.

© 2020 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Baseline salivary levels of C3 and C3c in patients with periodontitis and periodontally healthy controls. The scatter dot‐plots illustrate salivary levels of (A) C3 (μg/mL) and (B) C3c (μg/mL) in patients with periodontitis (n = 18) and periodontally healthy controls (n = 15), (P < .0001). The horizontal lines show median levels
Figure 2
Figure 2
Area under curve (AUC) for C3 and C3c in identifying periodontitis from periodontal health at baseline. Receiver operating curves (ROC) of salivary A = C3 and B = C3c levels discriminating between patients with periodontitis and periodontally healthy controls at baseline. (A) C3, AUC = 0.91, CI = [0.81;1.00], (P < .001), (B) C3c, AUC = 0.84, CI = [0.69;1.00], (P < .001)
Figure 3
Figure 3
Pre‐ and post‐treatment levels of C3 and C3c in patients with periodontitis. The scatter dot‐plots illustrate salivary levels of (A) C3 (μg/mL) and (B) C3c (μg/mL) recorded at baseline and two‐, six‐, and twelve weeks post‐treatment in patients with periodontitis (n = 18). The horizontal lines show the median levels
Figure 4
Figure 4
Baseline salivary C3 and C3c levels in good and poor responders to non‐surgical periodontal treatment. The scatter dot‐plots illustrate baseline saliva levels of (A) C3 (P > .05) and (B) C3c (P < .05) in good responders (n = 10) compared with poor responders (n = 8). The horizontal lines show the median levels in the two groups
Figure 5
Figure 5
AUC for total C3 and C3c at baseline in identifying poor responders to non‐surgical periodontal treatment. ROC analysis of salivary baseline levels of A = C3 and B = C3c to discriminate between the good (n = 10) and the poor (n = 8) responders to periodontal treatment. (A) C3, AUC = 0.65, CI = [0.36;0.94], (P > .05) and (B) C3c, AUC = 0.80, CI = [0.59;1.00], (P < .05)

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