Whole saliva and the diagnosis of Sjögren's syndrome: an evaluation of patients who complain of dry mouth and dry eyes. Part 1: Screening tests

Sjögren's Syndrome (SS) is a common autoimmune disorder characterised by generalised desiccation, exocrine hypofunction and serologic abnormalities, More than 90% of the patients are women. Objective : to determine if whole saliva could be used to diagnose this disease. Setting: The study was conducted at the School of Dental Medicine, SUNY, at Stony Brook. Patients : There were 49 subjects (48F; 1M), the mean age was 54 ± 13 years. In order to be admitted into the study, they had to complain of dry mouth and dry eyes. Tests : Whole saliva was collected by the spitting method. “Screening Tests'” were employed to measure the salivary flow rate, pH, buffer capacity; lactobacillus and yeast concentrations. Chemical tests were performed to determine protein, albumin, sodium and amylase activity. Lacrimal dryness was assessed by the Schirmer and Rose-Bengal methods. Results: Based on the sialometric findings, the patients were divided into 3 groups: Group 1: those with abnormally low resting (RFR) and stimulated (SFR) flow rates; Group 2: those with a low RFR but normal SFR; and Group 3: those with normal salivary flow rates. The group 1 patients were unique: their saliva demonstrated a low pH and buffer capacity, high lactobacillus and yeast concentrations, decreased protein output and amylase activity, and elevated albumin and sodium. Moreover, virtually all of them had abnormally low lacrimal flow rates. Conclusions : The findings suggested that whole saliva could be used to provisionally diagnose SS. Critical to this diagnosis was an abnormally low stimulated whole saliva flow rate. Other requisites included a low resting flow rate, the presence of dry mouth and dry eyes and evidence of lacrimal hypofunction. All of these attributes can easily be obtained by dentists in their clinics.     

Proteomic analysis revealed the altered tear protein profile in a rabbit model of Sjögren's syndrome‐associated dry eye

Sjögren's syndrome (SS) is an autoimmune disease that results in pathological dryness of mouth and eye. The diagnosis of SS depends on both clinical evaluation and specific antibodies. The goal of this study was to use quantitative proteomics to investigate changes in tear proteins in a rabbit model of SS‐associated dry eye, induced autoimmune dacryoadenitis (IAD). Proteomic analysis was performed by iTRAQ and nano LC‐MS/MS on tears collected from the ocular surface, and specific proteins were verified by high resolution MRM. It was found that in the tears of IAD rabbits at 2 and 4 weeks after induction, S100 A6, S100 A9, and serum albumin were upregulated, whereas serotransferrin (TF), prolactin‐inducible protein (PIP), polymeric immunoglobulin receptor (pIgR), and Ig gamma chain C region were downregulated. High resolution MRM with mTRAQ labeling verified the changes in S100 A6, TF, PIP, and pIgR. Our results indicated significant changes of tear proteins in IAD rabbits, suggesting these proteins could potentially be used as biomarkers for the diagnosis and prognosis of dry eye. Several of these proteins were also found in the tears of non‐SS dry eye patients indicating a common basis of ocular surface pathology, however, pIgR appears to be unique to SS.     

Medication in elderly people: its influence on salivary pattern,signs and symptoms of dry mouth

doi:10.1111/j.1741‐2358.2009.00293.x
Medication in elderly people: its influence on salivary pattern, signs and symptoms of dry mouth Objective: To compare stimulated and non‐stimulated salivary flow, pH, buffering capacity and presence of signs and symptoms of hyposialie and xerostomia in elderly patients, with senile dementia using medication and healthy elderly subjects not using medication. Methods: Forty individuals (mean age: 68.5 years) were divided into two groups, according to the use (G1) or non‐use (G2) of medication and the presence (G1) or absence (G2) of senile dementia. Data with reference to the general health condition, use of medication and the patient’s complaints were collected during anamnesis. Clinical examination identified signs associated with hyposialie and xerostomia. Stimulated and non‐stimulated saliva flow, pH and buffering capacity were verified. Results: The stimulated saliva flow in both groups was below normal parameters. The drugs used by individuals in G1 showed xerostomic potential. Individuals with a higher consumption of xerostomic medication presented with dry and cracked lips. A significant negative relationship was found between drugs consumption and the buffering capacity (p < 0.001), and the resting saliva flow rate (p = 0.002). Conclusion: The use of medication increases the chance that an elderly person may present signs related to xerostomia and alterations in stimulated saliva flow and buffering capacity.     

Relationship of stimulated whole saliva cortisol level with the severity of a feeling of dry mouth in menopausal women

doi: 10.1111/j.1741‐2358.2010.00403.x Relationship of stimulated whole saliva cortisol level with the severity of a feeling of dry mouth in menopausal women Objectives: To evaluate the relationship of stimulated whole saliva cortisol level with the severity of a feeling of dry mouth (DM) in menopausal women. Background: A feel of DM is a major complaint for many elderly individuals and strongly associated with the menopause. The exact mechanisms that mediate sensation of DM in menopausal women have not been firmly established. Methods: A case–control study was carried out on 104 selected menopausal women with/without a feeling of DM, conducted at the Clinic of Oral Medicine, Tehran University of Medical Sciences. Xerostomia Inventory (XI) score was used as an index of DM severity. Stimulated whole saliva cortisol concentration (stimulated by chewing standard‐sized paraffin for 60 s) was measured by ELISA. Statistical analysis by Student’s t‐test and Spearman correlation was used. Results: The mean cortisol concentration of saliva, but not saliva cortisol output, was significantly higher in the cases than in the controls. There was significant positive correlation between XI score and concentration (r = 0.357, p = 0.000) or output (r = 0.223, p = 0.017) of stimulated whole saliva cortisol. Conclusions: It appears that stimulated whole saliva cortisol is high in menopausal women with a feeling of DM.     

Salivary gland lymphocytes in primary Sjogren's syndrome lack lymphocyte subsets defined by Leu-7 and Leu-11 antigens

Primary Sjogren's Syndrome (SS) is an autoimmune disease characterized by dry eyes and dry mouth due to lymphocytic infiltration of lacrimal and salivary glands. Biopsies of their salivary glands provided an opportunity to characterize the phenotypic and functional properties of inflammatory site lymphocytes. We found that the salivary gland lymphocytes (SGL) of SS patients differed from the peripheral blood lymphocytes of the same patients because: a) SGL lacked lymphocytes reactive with anti-Leu-7 and anti-Leu-11 monoclonal antibodies; b) SGL lacked natural killer (NK) activity; and c) SGL lacked the ability to suppress polyclonal B cell responses in the presence of complement fragment C3a, a function that requires the presence of Leu-7+ cells. These studies also showed that the SGL of SS patients differed from tonsillar lymph node (LN) lymphocytes of immunologically normal individuals because tonsillar LN contained Leu-7+ T cells, and tonsillar LN could suppress polyclonal B cell responses in the presence of the complement fragment C3a. The absence of this regulatory subset in the salivary glands of SS patients may contribute to pathogenesis, because these cells may be important in the suppression of polyclonal antibody synthesis and in the elimination of neoplastic or viral infected cells.     

Impact of dry mouth conditions on oral health-related quality of life in older people

Objective: The aim of the present study was to evaluate the impact of dry mouth conditions on oral health‐related quality of life in frail old people, residents at community care centers. Further, reliability and validity of a visual analogue scale (VAS) for dry mouth symptoms were determined within the study cohort. Background: In old people functional, social and psychological impacts of oral conditions are associated with an overall sense of well being and general health. Subjective dry mouth and reduced saliva flow are common disorders in old people caused by disease and medication. Thus, dry mouth conditions may be determinants for compromised oral health‐related quality of life in old people. Method: In total, 50 old people living at service homes for the old people were asked to answer questionnaires on subjective dry mouth (VAS) and Oral Health Impact Profile (OHIP14) for oral health‐related quality of life. Saliva flow was estimated by absorbing saliva into a pre‐weighed cotton roll. Results: The final study cohort comprised 41 old people (aged 83–91 years). Significant associations were identified between both objective and subjective dry mouth and overall or specific aspects of oral health‐related quality of life. Conclusion: Dry mouth (objective and subjective) is significantly associated with oral health‐related quality of life strengthening the value of monitoring dry mouth conditions in the care of frail old people.     

Enhancing the quality of life in elderly women through a programme to improve the condition of salivary hypofunction

doi: 10.1111/j.1741‐2358.2011.00594.x Enhancing the quality of life in elderly women through a programme to improve the condition of salivary hypofunction Objective: The purposes of this study were to examine the effects of oral exercise intended to improve the function of the oral cavity in the elderly and their quality of life to pave the way for the development of oral‐health promotion programmes geared towards the elderly. Methods: The subjects were 78 female Koreans who resided in Seoul and were aged 65 years and older. During a 3‐month period, an oral function promotion programme was conducted twice a week, between 10.00 am and 12.00 pm , applying oral exercise suggested by a Japanese public health centre. A survey was conducted by interviewing the selected women to determine the state of their subjective dry mouth, quality of life related to oral health and jaw functional limitation. Their opening, unstimulated whole saliva and pronunciation speed were measured before and after the oral function exercise programme. Results: The subjects showed a significant improvement in subjective dry mouth symptoms, relevant behaviour, the level of discomfort caused by dry mouth and subjective jaw functional limitation during mastication and swallowing and emotional expression after receiving the oral exercise. After the oral exercise, there was a significant increase in mouth opening, unstimulated whole saliva and speaking speed (‘patakala’ pronunciation) after oral exercise. There was also significant progress in their quality of life related to oral health. Overall improvement in subjective dry mouth symptoms and relevant behaviour over time after oral exercise had a positive correlation with the level of improvement in discomfort triggered by dry mouth and mastication. The level of improvement in OHIP‐14 had a positive correlation with the level of overall improvement in dry mouth symptoms and behaviour, the level of improvement in discomfort by dry mouth and that in mastication and swallowing. Conclusion: This study showed the effects of the oral function promotion programme and correlation of oral condition and oral health‐related quality of life. It is suggested that this oral function promotion programme has positive effects on both objective and subjective oral conditions. It is strongly recommended that this programme, along with other oral health promotion programmes, be implemented to improve oral function and oral health‐related quality of life for the elderly.     

Relationship of serum and saliva calcium, phosphorus and alkaline phosphatase with dry mouth feeling in menopause

doi: 10.1111/j.1741‐2358.2012.00619.x Relationship of serum and saliva calcium, phosphorus and alkaline phosphatase with dry mouth feeling in menopause Objectives: The aim of this study was to compare serum and saliva calcium, phosphorus and alkaline phosphatase of menopausal women with/without dry mouth (DM) feeling. Background: The composition of saliva in menopause women with/without DM feeling is different. Some of these differences are in hormones that are related to bone turnover. Methods: A case–control study was carried out on 60 selected menopausal women aged 45–79 years with or without DM feeling (30 as case, 30 as control), conducted at the Clinic of Oral Medicine, Tehran University of Medical Sciences. The phosphorus concentration was measured by photometrical measurement of the blue colour formed after the addition of ammonium molybdate and stannous chloride; calcium was measured by Arsenazo reaction; and alkaline phosphatase by the pNPP‐AMP method. Statistical analysis of Student’s t‐test was used. Results: The mean serum phosphorus and alkaline phosphatase, stimulated and unstimulated saliva calcium and alkaline phosphatase levels were significantly higher in the menopausal women suffering from DM. There were no significant differences between groups regarding saliva phosphorus and serum calcium concentration. Conclusion: Calcium, phosphorus and alkaline phosphatase appear associated with DM feeling in menopause.     

Pathogenic effect of interleukin-17A in induction of Sj?gren's syndrome-like disease using adenovirus-mediated gene transfer

Introduction  

Sj?gren's syndrome (SS) involves a chronic, progressive inflammation primarily of the salivary and lacrimal glands leading to decreased levels of saliva and tears resulting in dry mouth and dry eye diseases. Seminal findings regarding T_H17 cell populations that secrete predominantly interleukin (IL)-17A have been shown to play an important role in an increasing number of autoimmune diseases, including SS. In the present study, we investigated the function of IL-17A on the development and onset of SS.     

A reference guide to drugs and dry mouth – 2nd edition

Xerostomia (dry mouth) is an uncomfortable and potentially harmful oral symptom which is usually caused by a decrease in the secretion rate of saliva (salivary gland hypofunction, or SGH). It is more prevalent in the elderly population, primarily due to their increased use of drugs and their susceptibility to disease. Many drugs and drug classes have been linked to xerostomia; the xerogenic effect increases when many drugs are taken concurrently. This Reference Guide to Drugs and Dry Mouth is designed to allow the reader to rapidly identify those pharmacologic agents which have the capacity to induce xerostomia and SGH. Xerogenic drugs can be found in 42 drug categories and 56 sub-categories. A guide to the management of drug-induced SGH and xerostomia is also provided.     

Comparison of the effect of the linseed extract Salinum® and a methyl cellulose preparation on the symptoms of dry mouth

The effect of a linseed extract Salinum® and a sodium carboxymethyl cellulose preparation called MAS-84 was compared with regard to its effect on the symptoms of dry mouth. Twenty patients with xerostomia, who had been treated for cancer in the head and neck by radiation were recruited from the clinic for maxillofacial surgery, Malmö University Hospital. Following radiation treatment the salivation was severely reduced. The symptoms of a general feeling of a dry mouth, difficulties in chewing and swallowing, taste disturbances, problems with speech and mouth burning were registered on a subjective verbal rating scale. In addition plaque index and gingival bleeding index were determined. The study design was crossover and performed single blind. The experimental period was 7 weeks. The patients were randomly divided into 2 groups, One group used Salinum® and the other MAS-84 for 3 weeks. The fourth week was a wash out period and for the next three weeks the patients shifted preparation. Each of the preparations was used ad libitium. Registrations of the various parameters were undertaken on days 0, 7 and 21 of the respective period. At the initial examination all patients reported considerable disturbances from mouth-dryness. These symptoms were reduced in 15 patients during the Salinum® period and in 9 during the MAS-84 period. The relief was significantly more pronounced during the use of Salinum® compared to that during the use of the methyl cellulose preparation. On day 21 plaque and gingival bleeding were significantly reduced during the Salinum® period but not during the MAS-84 period. The results of the present study confirm those of a previous pilot study and indicate that the linseed mucilage significantly reduced the symptoms of dry mouth. This effect increased with increasing time of saliva substitute use. The linseed mucilage Salinum® appeared to be a suitable saliva replacement in mouth dry patients.     

The effect of Salinum on the symptoms of dry mouth: a pilot study

The effect of a new saliva substitute. Salinum®, was tested in 37 patients with severe symptoms of reduced salivation. The majority of the patients had suffered from hyposalivation and dry mouth for more than 8 years. The saliva substitute consisted of a water soluble extract of linseed. The physical properties of this extract are similar to those of the glycoproteins of the salivary secretions. The patients used the saliva substitute for a seven days period. Prior to the use of the extract the patients reported that the most severe symptoms of decreased salivation were a feeling of dryness in the mouth and burning sensations in the tongue, pharynx and oesophagus, The majority of the patients reported that the use of Salinum reduced the symptoms of hyposalivation. Great variation in effect occurred from patient to patient. Generally the patients with the most severe symptoms experienced the greatest relief of the symptoms when they used Salinum. Although of short duration the results of this pilot study indicate that an extract of linseeds may compensate for some aspects of the consequences of reduced salivation. Further studies are needed to elucidate the feasibility of the extract as saliva replacement.     

在肽库中筛选抗磷脂抗体的小肽抑制剂

β２糖蛋白Ⅰ（ｂｅｔａ－２－ｇｌｙｃｏｐｒｏｔｅｉｎ Ⅰ,β２ＧＰＩ）是一分子量为５０ ｋＤ的糖蛋白．从抗磷脂抗体综合症（Ａｎｔｉｐｈｏｓｐｈｏｌｉｐｉｄ ａｎｔｉｂｏｄｉｅｓ ｓｙｎｄｒｏｍ ,ＡＰＳ）患者身上获得的抗体可直接与β２ＧＰＩ作用．以β２ＧＰＩ为目标分子,在噬菌体十五肽库中筛选抗β２糖蛋白Ⅰ抗体的小肽抑制剂．通过四轮亲和性筛选,噬菌体的回收率从１．２６×１０－ ４％ 增加到３．１９×１０－ ２％ ．随机挑取噬菌体克隆测定其与β２ＧＰＩ的结合活性及其对β２ＧＰＩ与自身抗体结合的抑制活性,其中部分噬菌体克隆表现出４０％ 的抑制活性．经ＤＮＡ 序列测定,得到一组相关序列．该结果为研究β２ＧＰＩ的抗原表位奠定了良好的基础．     

Decreased expression of antioxidant enzymes in the conjunctival epithelium of dry eye (Sjögren's syndrome) and its possible contribution to the development of ocular surface oxidative injuries

Previous studies have described elevated lipid peroxidase, myeloperoxidase and xanthine oxidoreductase/xanthine oxidase levels on the ocular surface of patients suffering from autoimmune dry eye (Sj?gren's syndrome, SS). Reactive oxygen species generated by various enzymatic systems may be dangerous to the eye if they are not sufficiently cleaved by antioxidants. Because antioxidants have not been investigated in dry eye, the aim of this study was to examine the expression of antioxidant enzymes that cleave reactive oxygen species and play a key role in antioxidant protection. Conjunctival epithelial cells of dry eye (SS) patients were obtained by the method of impression cytology using Millicell membranes. Normal eyes served as controls. In the conjunctival epithelium superoxide dismutase, catalase and glutathione peroxidase were examined immunohistochemically. The enzyme expression levels were determined by image analysis and statistical evaluation. In contrast to normal eyes, where antioxidant enzymes were highly expressed in the conjunctival epithelium, in dry eye their expression was much less pronounced in correlation with the increasing severity of dry eye symptoms. Our study suggests that the decreased expression of antioxidant enzymes in dry eye disease (SS) contributes to the development of anterior eye surface oxidative injuries.     

Detection of HIV-Gag p24-Specific Antibodies in Sera and Saliva of HIV-1-Infected Adults and in Sera of Infants Born to HIV-1-Infected Mothers

Secretory immunoglobulin A (IgA) is known to play an important role in the mucosal defense against a variety of pathogens. Although the role of IgA antibodies during sexual transmission of HIV is not clear, HIV-specific IgA antibodies have been detected in various mucosal secretions of HIV-infected individuals. Using a monoclonal antibody against human IgA, we established an ELISA system to detect anti-HIV p24 IgA antibodies in sera and saliva. We have analyzed the levels of anti-HIV p24 IgG and IgA antibodies in sera and saliva of 107 and 119 adults, respectively, with HIV infection at different clinical stages, and in the sera of 13 infants born to HIV-infected mothers. The level of anti-HIV p24 IgA antibodies was lower in sera and higher in saliva as compared to that of anti-HIV p24 IgG antibodies. Where the percentage of HIV-specific serum antibody-positive cases decreased with disease progression, that of saliva antibody-positive cases increased in AIDS patients. Among the 13 infants born to HIV-infected mothers, 7 infants were HIV-p24-specific serum IgA positive. These sera were negative for anti-HIV p24 secretory IgA, suggesting that some infants develop their own immune responses against HIV infection. Thus, the detection of HIV-specific IgA antibodies, especially in saliva, could be a simple and reliable test for the diagnosis of HIV infection.     

Identification of autoantibody biomarkers for primary Sjögren's syndrome using protein microarrays

Sj?gren’s syndrome (SS) is a chronic, progressive autoimmune disease primarily affecting women. Diagnosis of SS requires an invasive salivary gland tissue biopsy and a long delay from the start of the symptoms to final diagnosis has been frequently observed. In this study,we aim to identify salivary autoantibody biomarkers for primary SS (pSS) using a protein microarray approach. Immune-response protoarrays were used to profile saliva autoantibodies from patients with pSS (n = 514), patients with systemic lupus erythematosus(SLE, n = 513), and healthy control subjects (n = 513). We identified 24 potential autoantibody biomarkers that can discriminate patients with pSS from both patients with SLE and healthy individuals. Four saliva autoantibody biomarkers, anti-transglutaminase, anti-histone, anti-SSA, and anti-SSB, were further tested in independent pSS (n = 534), SLE (n = 534), and healthy control (n = 534) subjects and all were successfully validated with ELISA. This study has demonstrated the potential of a high-throughput protein microarray approach for the discovery of autoantibody biomarkers. The identified saliva autoantibody biomarkers may lead to a clinical tool for simple, noninvasive detection of pSS at low cost.     

Sorbitol Gum in Xerostomics: The Effects on Dental Plaque pH and Salivary Flow Rates1

Adequate salivary flow is important for patient comfort and maintenance of oral health. Xerostomia, or dry mouth, is a common clinical complaint. Masticatory and gustatory activity can stimulate salivary flow from functional salivary tissue and the use of sugarless mints and gums have been recommended to individuals who complain of xerostomia, but there are minimum clinical data. A clinical study assessing the effect on salivary flow rates and dental plaque pH of a sorbitol-sweetened chewing gum in subjects with the complaint of xerostomia was conducted. The chewing of the gum in this present study stimulated salivary flow in the subjects with xerostomia. Statistically significant stimulated whole mouth and parotid salivary flow rate increases were found when compared to unstimulated whole mouth and parotid salivary flow rates. Chewing of the sorbitol-sweetened gum also effectively reduced the drop in pH seen following the exposure to a fermentable carbohydrate. The findings of this present study indicate that chewing of a sorbitol-sweetened gum may be of benefit to patients with the complaint of xerostomia.     

检测抗核抗体谱对自身免疫性疾病的临床应用

目的:分析自身免疫性疾病患者抗核抗体谱检测结果,探讨抗核抗体谱检测在自身免疫性疾病诊断中的应用。方法:分别采用间接免疫荧光法和免疫印迹法检测130例自身免疫性疾病患者和20例健康人的ANA和抗核抗体谱。结果:ANA在各种自身免疫性疾病中均有一定的阳性检出率,ANA在SLE中的检出率最高,阳性率为89.6%,其次为ITP、MCTD和SS。抗核抗体谱中的各种自身抗体在不同的自身免疫性疾病中有不同的敏感性和特异性。结论:采用间接免疫荧光法对ANA的检测对自身免疫性疾病有重要的筛查意义,抗核抗体谱检测对自身免疫性疾病的诊断有重要意义。     

Biomarker profiles in serum and saliva of experimental Sj?gren's syndrome: associations with specific autoimmune manifestations

Introduction  

Sj?gren's syndrome (SS) is a systemic autoimmune disease that mainly targets the exocrine glands. The aim of this study was to investigate the involvement of 87 proteins measured in serum and 75 proteins analyzed in saliva in spontaneous experimental SS. In addition, we intended to compute a model of the immunological situation representing the overt disease stage of SS.