Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13.1 but no candidate gene was identified. In an international consortium we recruited 19 independent families comprising 107 individuals with pEDS to identify the locus, characterize the clinical details in those with defined genetic causes, and try to understand the physiological basis of the condition. In 17 of these families, we identified heterozygous missense or in-frame insertion/deletion mutations in C1R (15 families) or C1S (2 families), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway. These two proteins form a heterotetramer that then combines with six C1q subunits. Pathogenic variants involve the subunit interfaces or inter-domain hinges of C1r and C1s and are associated with intracellular retention and mild endoplasmic reticulum enlargement. Clinical features of affected individuals in these families include rapidly progressing periodontitis with onset in the teens or childhood, a previously unrecognized lack of attached gingiva, pretibial hyperpigmentation, skin and vascular fragility, easy bruising, and variable musculoskeletal symptoms. Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis.

Background: The detection of special bacterial species in patients with periodontitis is considered to be useful for clinical diagnosis and treatment. The collection of subgingival plaque samples is the common way for the determination of periodontopathic bacteria. However, recently, salivary analysis has been discussed as an advantageous future diagnostic method for periodontitis because it offers simple quantitative sampling and the possibility to assess various bacteria. The aim of this cross‐sectional study is to investigate whether there is a correlation between the results of different bacterial species in saliva and subgingival plaque samples from individuals with aggressive periodontitis (AgP) and chronic periodontitis (CP).Methods: Whole saliva and subgingival plaque samples from the deepest pocket of each quadrant were collected from 43 patients with CP and 33 patients with AgP. Twenty different bacterial species from both samplings were determined by the 16S ribosomal RNA‐based polymerase chain reaction with microarray technique.Results: All bacterial species were detected in salivary and subgingival plaque samples. For Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, as well as Actinomyces viscosus, Campylobacter rectus/showae, Prevotella intermedia, Parvimonas micra, Eubacterium nodatum, and Campylobacter gracilis, a significant positive correlation between salivary and subgingival plaque samples was detected in patients with both types of periodontitis. There were no significant differences in bacteria in salivary and subgingival plaque samples between AgP and CP.Conclusion: Salivary analysis might be discussed as a potential alternative to subgingival plaque sampling for microbiologic analysis in both AgP and CP.

Background: Salivary stress-related biomarkers in connection with periodontal disease have not been extensively studied. In addition to cortisol as a well-known marker of stress loading, chromogranin A (CgA) and α-amylase (AA) are supposed to link the activity of the neuroendocrine system to local and systemic immune functions and to be related to periodontitis. This study aims to determine CgA and AA in saliva and serum in periodontal health and disease to assess their potential relationship to periodontitis. Methods: Patients with aggressive (AgP) (n = 24) and chronic periodontitis (CP) (n = 34) as well as healthy control (CO) (n = 30) individuals participated in this study. CgA and AA were determined in saliva and serum with enzyme-linked immunosorbent assay and an adapted clinical amylase test; salivary cortisol was determined using mass spectrometry. Clinical parameters of periodontal disease were evaluated, and their possible correlations with stress-related biomarkers were assessed. Results: Significantly higher CgA levels were found in the saliva of patients with AgP compared with those in patients with CP and CO individuals (P <0.001). Salivary cortisol levels were higher in the AgP group compared with those in patients with CP (P <0.05). No differences in serum CgA levels and salivary and serum AA activities were found among all groups. A positive correlation was revealed between salivary AA activity or salivary CgA levels and the extent of periodontitis (P <0.05). Conclusion: The results suggest an association of CgA and cortisol levels as well as AA activity in saliva with periodontitis, especially a significant relationship of salivary CgA and cortisol to AgP.

Background: This study aims to investigate calcium‐binding myeloid‐related protein (MRP)‐8/14 in the saliva and serum of individuals with periodontitis and periodontally healthy individuals for the assessment of its role in the pathogenesis and clinical diagnosis of periodontitis.Methods: This cross‐sectional study includes 56 patients with periodontitis and 44 periodontally healthy individuals. Saliva and serum were collected for the detection of MRP‐8/14 and calcium levels. Periodontopathic bacteria were determined by polymerase chain reaction in saliva. Correlations between salivary and serum MRP‐8/14 levels and clinical parameters, bacteria, and calcium were analyzed with Pearson correlation in a multiple regression model. MRP‐8/14 levels were documented with receiver operating characteristic (ROC) curves.Results: Compared with healthy individuals, MRP‐8/14 levels were significantly higher in both the saliva and serum of patients with periodontitis, but calcium was increased only in saliva. A high diagnostic potential of salivary MRP‐8/14 was detected for periodontitis (ROC = 0.86). Salivary MRP‐8/14 levels correlated significantly with the presence of the periodontopathogen Treponema denticola, as well as with the clinical parameters of periodontitis.Conclusion: MRP‐8/14 in saliva might be a potential diagnostic parameter for periodontal disease.