LDI - Saliva Data Base

The LDI/JGH Databank for Saliva Specimens is the only bio-bank of saliva specimens in Canada. Its collection of samples (more than 2,100 to date) have been used to test for bio-markers for Alzheimer and Parkinson diseases, diabetes, scleroderma, orofacial pain, breast cancer, and microbiota.

Saliva is a complex secretion whose components have a well-documented role in health and disease. In addition to its lubricant and enzyme characteristics, saliva contains biochemical systems known to be involved in soft-tissue repair, many antibacterial, antiviral and antifungal components including lysozyme, lactoferrin, salivary peroxidase, histatins, and various antioxidants. Saliva is a unique fluid and interest in it as a diagnostic medium has advanced exponentially in the last 10 years. Advances in the use of saliva as a diagnostic fluid have been affected by current technological developments. These advances in technology have helped to move saliva beyond ascertaining oral health characteristics to current assessment of essential features of overall health.

All research on human tissues involves the creation of some repository in which to store them. We are currently seeing unprecedented proliferation in the number and capacity of these biobanks, whether in terms of storage duration, quantities of banked specimens, bank sites or related financial issues. In addition, the convergent development of electronic data processing and biological material preservation gives rise to large-scale storage and leading-edge human tissue studies. Data banks and biobanks are a valuable resource providing evidence that far exceeds the anecdotal knowledge culled from limited quantities of information or biological specimens. Their scientific value lies in the possibility of collecting data or specimens from hundreds or even thousands of individuals. Analysis of large amounts of data and specimens increases the statistical power of research outcomes and thereby enhances their validity. Biobanks owe their considerable worth to these larger quantities. The possibility of correlating banked data and, also, correlating those data and biological material multiplies research resources and improves the chances of gaining new knowledge. While this technical capability allows for many such correlations, it also puts respect for privacy and personal autonomy at greater risk.

Sample Storage

Specimens will be kept at the Lady Davis Institute under the responsibility of Dr. Hyman Schipper and Dr. Mervyn Gornitsky. The collection will be done at least 30 min after food or liquid ingestion in sterilized centrifuge tubes after participants have received their routine check-up in the morning. To minimize temporal fluctuations in salivary redox homeostasis, all samples may be collected between 09:00am and 12:00pm. At the end of the collection period, the tube will be sealed, kept at 4^oC and conveyed to the laboratory for processing as quickly as possible. Prior to analysis, the saliva will be centrifuged at 10,000 rpm for 20 min at 4 °C. The supernatant will be withdrawn and stored in small aliquot tubes at -80 °C until analysis. The salivary samples may be stored until all the saliva is used or destroyed in the laboratory of Dr. Hyman Schipper at the Lady Davis Institute.

Neurotranslational Research

Oxidative stress has been documented in tissues and biofluids of subjects with sporadic Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI); our study demonstrated that levels of protein carbonyls, a marker of oxidative stress, exhibit robust diurnal variation in the saliva of normal elderly, MCI, and AD subjects. These observations raise the intriguing possibility that various oral pathologies and their responsiveness to therapeutic interventions may be impacted by diurnal (possibly circadian) fluctuations in salivary redox homeostasis. Another study related to AD revealed that tau and phosphorylated-tau proteins are universally present in human saliva; these preliminary results provided the basis for an ongoing Weston Brain Institute grant.

Periodontal Disease

Periodontal disease is associated with increased oxidative modification of salivary DNA, lipids, and proteins. Augmented salivary total antioxidant capacity may represent an adaptive response to oxidative stress. Salivary amylase, transferrin, and human IgG1 heavy chain fragments are particularly prone to enhanced oxidation in periodontitis.

Diabetes

Diabetes mellitus (DM) is associated with increased oxidative modification of salivary DNA and proteins. Salivary redox homeostasis is perturbed in DM and may inform on the presence of the disease and efficacy of therapeutic interventions.

Scleroderma

SSc subjects have more missing teeth, more periodontal disease, less saliva production, smaller interincisal distance and poorer oral health-related quality of life (HRQoL) than controls. These data can be used to develop targeted interventions to improve oral health and HRQoL in SSc. We recommend the use of adaptive devices such as flossers, powered oscillating-rotating toothbrushes and orofacial exercise to improve oral health. Aesthetics represented by facial changes may be ameliorated by various home-based exercise programs. These include mouth stretching, connective tissue massage, Kabat’s technique and a kinesitherapy program, which may improve mouth functioning and opening.

Orofacial Pain

Salivary C-Reactive Protein levels appear to be related to temporomandibular disorder and to pain intensity, regardless of severity of the pain. Salivary Nerve Growth Factor (NGF) levels are associated with pain intensity only among those with severe pain, and NGF seems to be a biomarker specific for pain severity Amylase levels were not associated with pain intensity.

Breast Cancer

Our studies found that levels of 8-hydroxy-2' -deoxyguanosine (8-OxodG) were significantly reduced in saliva of patients with breast cancer relative to control values, whereas salivary levels of the isoprostane 8-epi-Prostaglandin F2α (8-epi-PGF2α) were significantly elevated among patients with breast cancer relative to controls. In contrast, protein oxidization and total antioxidant capacity (TAC) were not associated with breast cancer. These results indicate differential salivary levels of 8-OxodG and 8-epi-PGF2α between patients with breast cancer and controls.

Microbiota

This is a new project where we intend to characterize the baseline state of the oral cavity microbiota, i.e. the community of microbes associated with the human body, through saliva sampling in order to assess how modifications in the microbiota are related to diseases. This is in line with the goals of the Human Microbiome Project Consortium.

Relevant Publications

Wang J, Schipper HM, Velly AM, Mohit S, Gornitsky M. Salivary Biomarkers of Oxidative Stress: a Critical Review. Free Radical Biology and Medicine 2015; 85:95–104.

Baron M, Hudson M, Tatibouet S, Steele R, Lo E, Gravel S, Gyger G, El Sayegh T, Pope J, Fontaine A, Masseto A, Matthews D, Sutton E, Thie N, Jones N, Copete M, Kolbinson D, Markland J, Nogueira-Filho G, Robinson D, Gornitsky M. “The Canadian Systemic Sclerosis Oral Health Study III: Relationship Between Disease Characteristics and Oro-facial Manifestations in Systemic Sclerosis" Arthritis Care & Research, May 2015;67(5):681-90.

Baron M, Hudson M, Tatibouet S, Steele R, Lo E, Gravel S, Gyger G, El Sayegh T, Pope J, Fontaine A, Masseto A, Matthews D, Sutton E, Thie N, Jones N, Copete M, Kolbinson D, Markland J, Nogueira-Filho G, Robinson D, Gornitsky M. “The Canadian systemic sclerosis oral health study II: The Relationship Between Oral and Global Health-Related Quality of Life in Systemic Sclerosis”. Rheumatology April 2015: 54(4): 692-6

Baron M, Hudson M, Tatibouet S, Steele R, Lo E, Gravel S, Gyger G, El Sayegh T, Pope J, Fontaine A, Masseto A, Matthews D, Sutton E, Thie N, Jones N, Copete M, Kolbinson D, Markland J, Nogueira-Filho G, Robinson D, Gornitsky M. “The Canadian systemic sclerosis oral health study: orofacial manifestations and oral health-related quality of life in systemic sclerosis compared with the general population”. Rheumatology August 2014;53:1386-1394.

Su H, Velly AM, Salah MH, Benarroch M, Trifiro M, Schipper HM, and Gornitsky M. “Altered Redox Homeostasis in Human Diabetes Saliva”. Journal of Oral Pathology and Medicine. 2012 Mar;41(3):235-241.

Su H, Baron M, Benarroch M, Velly AM, Gravel S, Schipper HM, Gornitsky M. “Altered salivary redox homeostasis in patients with systemic sclerosis.” J Rheumatol. 2010 Sep;37(9):1858-63.

Su H, Gornitsky M, Velly AM, Yu H, Benarroch M, Schipper HM. “Salivary DNA, lipid, and protein oxidation in nonsmokers with periodontal disease.” Free Radical Biology & Medicine. 2009 Apr 1;46(7):914-21.

Su H, Gornitsky M, Geng G, Velly AM, Chertkow H, Schipper HM. ”Diurnal variations in salivary protein carbonyl levels in normal and cognitively impaired human subjects.” AGE Vol. 30, No. 1. 1-9, Mar. 2008