Identification of potential salivary biomarkers for Sjögren's syndrome with an untargeted metabolomic approach.

INTRODUCTION: Despite the rise of metabolomics over the past years, and particularly salivary metabolomics, little research on Sjögren's syndrome (SS) biomarkers has focused on the salivary metabolome. OBJECTIVES: This study aims to identify metabolites that could be used as biomarkers for SS. METHODS: Using the software called XCMS online, the salivary metabolic profiles obtained with liquid chromatography coupled to high-resolution mass spectrometry for 18 female SS patients were compared to those obtained for 22 age-matched female healthy controls. RESULTS AND CONCLUSION: A total of 91 metabolites showed differential expression in SS patients. A putative identification was proposed with the use of a database for 37 of these metabolites and, of these, 16 identifications were confirmed. Given the identified metabolites, some important metabolic pathways, such as amino acid metabolism, purine metabolism, or even the citric acid cycle seem to be affected. Through the analyses of the ROC (receiver operating characteristic) curves, three metabolites, namely alanine, isovaleric acid, and succinic acid, showed both good sensitivity (respectively 1.000, 1.000, and 0.750) and specificity (respectively 0.692, 0.615, and 0.692) for identifying SS and could then be interesting biomarkers for a potential salivary diagnosis test.

Variability of systemic and oro-dental phenotype in two families with non-lethal Raine syndrome with FAM20C mutations.

BACKGROUND: Raine syndrome (RS) is a rare autosomal recessive bone dysplasia typified by osteosclerosis and dysmorphic facies due to FAM20C mutations. Initially reported as lethal in infancy, survival is possible into adulthood. We describe the molecular analysis and clinical phenotypes of five individuals from two consanguineous Brazilian families with attenuated Raine Syndrome with previously unreported features. METHODS: The medical and dental clinical records were reviewed. Extracted deciduous and permanent teeth as well as oral soft tissues were analysed. Whole exome sequencing was undertaken and FAM20C cDNA sequenced in family 1. RESULTS: Family 1 included 3 siblings with hypoplastic Amelogenesis Imperfecta (AI) (inherited abnormal dental enamel formation). Mild facial dysmorphism was noted in the absence of other obvious skeletal or growth abnormalities. A mild hypophosphataemia and soft tissue ectopic mineralization were present. A homozygous FAM20C donor splice site mutation (c.784 + 5 g > c) was identified which led to abnormal cDNA sequence. Family 2 included 2 siblings with hypoplastic AI and tooth dentine abnormalities as part of a more obvious syndrome with facial dysmorphism. There was hypophosphataemia, soft tissue ectopic mineralization, but no osteosclerosis. A homozygous missense mutation in FAM20C (c.1487C > T; p.P496L) was identified. CONCLUSIONS: The clinical phenotype of non-lethal Raine Syndrome is more variable, including between affected siblings, than previously described and an adverse impact on bone growth and health may not be a prominent feature. By contrast, a profound failure of dental enamel formation leading to a distinctive hypoplastic AI in all teeth should alert clinicians to the possibility of FAM20C mutations.

Mapping Salivary Proteases in Sjögren's Syndrome Patients Reveals Overexpression of Dipeptidyl Peptidase-4/CD26.

Sjögren's Syndrome (SS) is an autoimmune exocrinopathy characterized by the progressive damage of salivary and lacrimal glands associated with lymphocytic infiltration. Identifying new non-invasive biomarkers for SS diagnosis remains a challenge, and alterations in saliva composition reported in patients turn this fluid into a source of potential biomarkers. Among these, proteases are promising candidates since they are involved in several key physio-pathological processes. This study evaluated differentially expressed proteases in SS individuals' saliva using synthetic fluorogenic substrates, zymography, ELISA, and proteomic approaches. Here we reported, for the first time, increased activity of the serine protease dipeptidyl peptidase-4/CD26 (DPP4/CD26) in pSS saliva, the expression level of which was corroborated by ELISA assay. Gelatin zymograms showed that metalloproteinase proteolytic band profiles differed significantly in intensity between control and SS groups. Focusing on matrix metalloproteinase-9 (MMP9) expression, an increased tendency in pSS saliva (p = 0.0527) was observed compared to the control group. Samples of control, pSS, and sSS were analyzed by mass spectrometry to reveal a general panorama of proteases in saliva. Forty-eight protein groups of proteases were identified, among which were the serine proteases cathepsin G (CTSG), neutrophil elastase (ELANE), myeloblastin (PRTN3), MMP9 and several protease inhibitors. This work paves the way for proteases to be explored in the future as biomarkers, emphasizing DPP4 by its association in several autoimmune and inflammatory diseases. Besides its proteolytic role, DPP4/CD26 acts as a cell surface receptor, signal transduction mediator, adhesion and costimulatory protein involved in T lymphocytes activation.

Rehabilitation of an adolescent with autosomal dominant amelogenesis imperfecta: case report.

Amelogenesis imperfecta is a hereditary condition that affects tooth enamel without systemic involvement. In the most severely affected patients, teeth can present alterations in enamel thickness, color and shape, all which compromise aesthetic appearance and mastigatory function. Several treatment options have been described to rehabilitate these patients, ranging from preventive intervention to a prosthodontic approach. Advances in the search for new techniques and bonding materials have provided less invasive treatment options. This study discusses the importance of preventive procedures and describes the clinical procedures of aesthetic and functional rehabilitation of a Brazilian adolescent with autosomal dominant amelogenesis imperfecta (ADAI) involving the use of direct and indirect resin composite restorations.

Dental panoramic indices and fractal dimension measurements in osteogenesis imperfecta children under pamidronate treatment.

OBJECTIVES: To verify radiomorphometric indices and fractal dimension (FD) in dental panoramic radiographs (DPRs) of children with different types of osteogenesis imperfecta (OI) and also to verify the effect of pamidronate (PAM) treatment in such panoramic analyses. METHODS: In this retrospective study, 197 DPRs of 62 children with OI Types I, III and IV who were in treatment with a comparable dosage of intravenous PAM were selected. The mandibular cortical width (MCW), mandibular cortical index, visual estimation of the cortical width and FD of three standardized trabecular and cortical mandibular regions of interest were obtained from the radiographs. Factorial analysis of variance and Fisher test were used to compare FD and MCW measurements in children with different types of OI for different PAM cycles. RESULTS: Children with all types of OI have thinner and more porous mandibular cortices at the beginning of treatment. There were significant differences between MCW and FD of the cortical bone, regarding different types of OI and number of PAM cycles (p = 0.037 and p = 0.044, respectively). FD measurements of the trabecular bone were not statistically different among OI types nor were PAM cycles (p > 0.05). CONCLUSIONS: Children with OI presented cortical bone alterations after PAM treatment. Both MCW and the FD of the cortical bone were higher in children with OI after PAM treatment. It is argued that cortical bone should be considered for analyzing patients with OI, as well as to monitor the progress of PAM treatment.

Taurodontism in Brazilian patients with tooth agenesis and first and second-degree relatives: a case-control study.

AIM: An association between tooth agenesis and taurodontism has been suggested. To verify if tooth agenesis and taurodontism are associated within families and specific patterns of tooth agenesis, this study aims to compare the frequency of taurodontism in patients with nonsyndromic familial tooth agenesis, their first and second-degree relatives with complete permanent dentition and a control group of unrelated healthy individuals with complete permanent dentition. MATERIALS AND METHODS: Panoramic radiographs of patients with nonsyndromic familial tooth agenesis, their first and second-degree relatives and a control group of individuals with complete permanent dentition were examined. Taurodontism was assessed on permanent mandibular first molars. The difference in the frequency of taurodontism among the studied groups was tested with Fisher's Exact Test. RESULTS: Seventeen families with nonsyndromic familial tooth agenesis were studied. The frequency of taurodontism was 29% in patients with tooth agenesis, 10.3% in their first and second degree relatives, and 6.6% in the control group. A significant statistical difference among the studied groups was observed (p=0.002). Taurodontism was proportionally more frequent in patients with a higher number of absent teeth. It was mainly observed in patients from families in which the proband was diagnosed with oligodontia. CONCLUSIONS: Taurodontism is more frequent in nonsyndromic familial tooth agenesis. Individuals in families with second premolar and molar oligodontia are more likely to have taurodontism, even the individuals with complete dentition. This association could define a subphenotype for future genetic studies of dental development.