Saliva as a sample for diagnosis. Sounds excellent right? No more blood samples, no more pricks…. Well saliva is a clinically informative, biological fluid and can be useful prognosis, diagnosis and follow up of patients with various diseases. The process of collection is simple, It is ideal for detection of disease as it contains specific soluble biomarkers. In future, salivary diagnosis can be simplified and become a more useful pain free diagnostic aid to human health. Salivary diagnostics is a dynamic and emerging field using nanotechnology and molecular diagnostics to help aid in the diagnosis. Diseases are diagnosed via
Patient reported symptoms
Examination and a medical history obtained by a Doctor
Analysis of blood , urine and other biological samples.
The currently available biomarkers for infections include ions, antibodies, hormone levels, and a variety of disease-specific biomarkers. These assays are not available in all labs and are sent to distant places for analysis. The whole procedure is costly and time taking. Samples in form of swabs are currently collected only to diagnose Streptococcus pyogenes to diagnose “strep throat”, or a mucosal biopsy for suspected oral cancer. The concept of using saliva as a sample will be helpful in population studies and in children in whom taking proper samples is always troublesome.
Oral samples that are useful for diagnosis are Saliva, Gingival crevicular fluid, oral swabs, dental plaques and volatiles. Significant sample will be the one which collects DNA for the oral cavity. This principle has been used in forensic medicine. The other areas where saliva can be used as a sample are for hormonal assays ( Cortisol, Estriol, Estrogen and Testosterone).
Saliva in Cardiovascular disease –
C-reactive protein – This is an acute phase reactant and can be monitored using salivary samples. The problem is that CRP may be elevated in some periodontal diseases
Salivary immunoglobulins are elevated in coronary artery diseases. Salivary IgA can be used in conjunction with Electrocardiogram following myocardial infarction.
Elevated Lysozyme levels can be used as a marker for oral infection and hyperglycemia. There has been significant association between salivary Lysozyme with hypertension.
Saliva in Renal disease –
Generally some markers are associated with end stage renal disease. The list of markers included cortisol, nitrite, uric acid, sodium, chloride, pH, amylase and lactoferrin. Some scientists have used colormetric test strips were used to monitor salivary nitrate and uric acid before and after hemodialysis. They have concluded that saliva testing could be used in patients to decide when the patient needs dialysis.
Salivary phosphate has been successfully used as a clinical biomarker for hyperphosphatemia, which is an important contributor to cardiovascular calcification in
chronic renal failure (CRF). Evaluation of phosphate levels in saliva correlates positively with serum creatinine and the glomerular filtration rate. Thus, salivary phosphate may provide a better marker than serum phosphate for the initiation of treatment of hyperphosphatemia in CRF
Salivary biomarkers in psychological research
Stress and pain are often interrelated events. Investigators have attempted to distinguish them using a variety of model systems that induce either stress or pain, and subjects are monitored for changes in salivary biomarkers. Typical markers that have been identified include salivary amylase, cortisol, substance P, lysozyme and secretory IgA. Pain responses in dental pulp have been specifically associated with neuropeptides including calcitonin gene-related peptide (CGRP), substance P, neurokinin A and neurokinin P. Salivary testosterone levels have been associated with increased aggressive behavior and also with athletic activities. Several reports relate cognitive behavior to levels of tryptophan and serotonin, the latter being monitored in saliva. It should be pointed out that for studies in psychological and behavior fields. collection of saliva samples can be helpful , as a blood draw may induce both stress and pain in some individuals.
Saliva in detection of systemic malignancies –
Tumor marker C125 has been identified in saliva of subjects with malignant ovarian tumors. Many other tumor markers and tumor suppressors are under evaluation.
Diabetes biomarkers
As far as Diabetes is concerned an oral test to monitor blood glucose would be highly desirable. Unfortunately, while it is relatively easy to measure salivary glucose, due to the multiple sources of this material in the oral cavity, salivary glucose levels do not correlate with blood glucose levels. However, several other approaches are under investigation. One method recently described was to demonstrate a unique proteomic signature in saliva obtained from Type-2 diabetics as compared to control saliva, with 65 proteins showing greater than a 2-fold change. Many of these proteins were associated with metabolic and immune regulatory pathways. While further studies are clearly needed, these findings suggest that there may indeed be a unique salivary biomarker profile associated with diabetes. Another interesting approach to detect Type 1 diabetic hyperglycemia involves measuring exhaled methyl nitrate. One more method under study is by using gingival crevicular blood as a measure of blood glucose. In a study of fifty four subjects, blood obtained during a routine periodontal exam was collected and compared to blood obtained with a finger-stick; the study showed good correlation between samples collected from the two sites.
Salivary diagnostics for autoimmune diseases
Major rheumatoid factor diseases include Lupus Erythematosis, Scleroderma, and Sjogren's syndrome. These autoimmune diseases are characterized by the production of autoantibodies that attack normal tissue. Sjogren's syndrome is a disease characterized by dryness of the eyes and mouth and it may occur as a primary or a secondary disease. The clinical symptoms in the primary form are more restricted and are associated with lacrimal and salivary gland dryness. In secondary Sjogren's syndrome, patients undergo one of the autoimmune diseases mentioned above before Sjogren's symptoms develop. For decades, the sjogren syndrome diagnosis has been based on oral examination, detection of blood biomarkers (autoantibodies to self-antigens (SS-A and SS-B), Rheumatoid factor and antinuclear antibodies, and by obtaining a confirmatory salivary gland biopsy. Studies are underway to using cutting-edge proteomics and genomics technologies. Saliva contained a series of biomarkers that could detect primary sjogren syndrome(pSS). In addition, the proteomic and genomic profile of these salivary markers reflected the damage to glandular cells, activated anti-viral immune response, or programmed cell death known to be involved in pSS pathogenesis. The value of these candidate salivary biomarkers for pSS diagnosis has been confirmed by quantitative realtime polymerase chain reaction (qRT-PCR) and immunoblotting techniques
Salivary biomarkers for infectious diseases
Many viral infections could be identified from salivary samples. These include a large range of Herpes viruses, Hepatitis viruses, HIV, Human Papillomavirus (HPV), Influenza virus, and Poliovirus. Fourteen bacterial pathogens were detected (by antibody, antigen or nucleic acid) including Escherichia coli, Mycobacterium tuberculosis, Helicobacter pylori, Treponema pallidum and a wide range of streptococcal species. Nonviral and non-bacterial infectious agents including Candida albicans, Toxoplama gondii, and Schistosoma mansoni were detectable, typically by antibodies to these infectious agents. These pathogens are responsible for both systemic and oral diseases.
Studies are currently underway to evaluate the efficacy of using Saliva as a clinical sample. Hopefully in future patients can keep aside their phobia for needles and concentrate more on their health. If this technology is successful it will aid in rapid and early diagnosis.
Adapted from - Saliva as a Diagnostic Fluid, Dent Clin North Am. 2011 January ; 55(1): 159–178. doi:10.1016/j.cden.2010.08.004.
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