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

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.

Host Modulation and Treatment of Periodontal Disease

“…Higher levels of complement activation in gingival tissues and gingival crevicular fluid (Hajishengallis et al 2020) and saliva (Grande et al 2020) of patients with periodontitis establish a clear role of complement in the pathogenesis of periodontitis. The central component of complement, C3, amplifies recruitment and phagocytosis by inflammatory leukocytes and is a promising therapeutic target for periodontitis (Skendros et al 2020).…”

Phase IIa clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation

“…The complement system is a central hub of innate immunity responsible for the induction and regulation of immune and inflammatory responses (16); Yet, its dysregulation or overactivation can drive pathological inflammation (17). In this context, gingival inflammation in patients with periodontitis is associated with enhanced complement activity (18)(19)(20), whereas mice lacking the central complement component C3, or the receptor for the complement anaphylatoxin C3a, are protected from gingival inflammation and alveolar bone loss (21)(22)(23).…”

Alternative C3 Complement System: Lipids and Atherosclerosis

“…Indeed, the serum showed a strong signal for C3c fragments, the final proteolysis product derived from C3 complement activation, when analyzed by Western blot, and a similar fragment was also found in purified agLDL ( Figure S2 ). C3c has been described as a biomarker of heart failure [ 44 ], periodontitis [ 45 ] or amyotrophic lateral sclerosis [ 46 ], but its role and function needs to be further investigated.…”