Analysis of the concentration and output of whole salivary constituents in patients with Sjögren's syndrome

In Sjögren's syndrome, salivary glands are affected, resulting in a diminished salivary flow. In the present study, the protein composition, sialic acid content and the amounts of calcium and phosphate of stimulated whole saliva from 43 patients with Sjögren's syndrome, were compared with those of control saliva samples from 17 healthy subjects. The absolute concentrations of albumin, cystatin C. cystatin S. total IgA and total protein, but not amylase, were increased significantly in both primary and secondary Sjögren's syndrome. The output/min of total protein, albumin, amylase, and IgA was, however, decreased in Sjögren patients. These results suggest that the diminished output of salivary defence factors, rather than their absolute concentrations, may be related to the oral health problems seen in Sjögren's syndrome patients.     

Minor salivary gland immunohistology in the diagnosis of primary Sjögren's syndrome

Background:  Focal lymphocytic infiltrates of minor salivary glands are considered target-organ related signs of Sjögren's syndrome. The percentages of plasma cells expressing IgA, IgG and IgM in minor salivary gland biopsies have also been suggested as useful in establishing a diagnosis of Sjögren's syndrome, and this study aimed at evaluating this method.
Methods:  All biopsies from patients under investigation for Sjögren's syndrome ( n  = 210) at our department during 4 years were analyzed for IgA, IgG and IgM producing cells by immunohistochemistry, and related to Sjögren classification parameters.
Results:  A focus score ≥1 was observed in 67/210 patients and the frequency of IgA producing cells was <70% in 42/210 patients. Sufficient clinical data for classification of disease were available for 57/210 patients. Patients were classified as having primary Sjögren's syndrome (pSS) ( n  = 9), secondary Sjögren's syndrome (sSS) ( n  = 12) or non-Sjögren's syndrome (non-SS) ( n  = 36). IgA expressing cells were significantly decreased ( P  < 0.01) and IgG expressing cells significantly increased ( P  < 0.02) in patients with pSS compared to non-SS. Also, increased numbers of salivary gland IgG producing plasma cells correlated with increased IgG serum levels ( P  < 0.001). However, there was no significant difference between sSS and non-SS with regard to IgA, IgG or IgM expressing cells in the glands.
Conclusions:  Our results support previous reports indicating the relevance of quantitative evaluation of Ig isotype expression in plasma cells in the clinical investigation of Sjögren's syndrome and further indicate a difference in plasma cell populations between pSS and sSS.     

Salivary gland function and changes in patients with oral lichen planus

Abstract – Saliva analysis, sialography and histopathologic examination of labial salivary glands were performed on patients with oral lichen planus. Diseases connected with salivary gland function were also recorded. Saliva analysis regarding secrection rate, pH and buffer capacity in unstimulated and stimulated saliva was permormed on 39 patients. 87% of the patients exhibired a low or very low unstimulated secretion rate, the mean value being 0.14 ml/min. The rate of stimulated saliva, pH and buffer capicity did not deviate from normal reference values. Sialographic examination was performed on 18 patients, corresponding to 36 major salivary glands. Radiologic changes were seen in 89% patients. Histopathologic examination was performed on 15 patients. Lymphocytic infiltration, acinar atrophy, fibrosis, fatty degeneration or ducral changes were observed in the minor glands of all patients. Different degrees of acinar atrophy were present in 93% of the patients. Lymphorytic infiltration was seen in 12 patients (80%) of whom three exhibited focal accumulation as in Sjögren's syndrome. Since decreased salivary secretion and symptoms of joint diseases and keratoconjunctivitis sicca were frequently present, over a third of the patients showed clinical signs comparable to those of Sjögren's syndrome. A high frequency of gastrointestinal and endocrine diseases was also recorded, which suggests that a general exo and endocrine influence may be present in patients with oral lichen planus.     

Cytokines in Sjögren's syndrome

Cytokines play a central role in the regulation of immunity and are often found to be deregulated in autoimmune diseases. Sjögren's syndrome is a chronic autoimmune disease characterized by inflammation and loss of secretory function of the salivary and lachrymal glands. This review highlights the current knowledge of the expression and the function of pro- and anti-inflammatory cytokines both locally and systemically in Sjögren's syndrome patients. In the salivary glands, saliva and serum of these patients, many pro-inflammatory cytokines are upregulated. Concomitantly, most anti-inflammatory cytokines are not detectable or are expressed at low levels. Besides a role in inflammation, cytokines are also thought to be involved in salivary gland dysfunction by directly interfering with the epithelial cells in the glands. Future research on the role of novel cytokines in Sjögren's syndrome in combination with a better understanding of the effect of cytokines on exocrine dysfunction will aide the identification of the best therapeutic targets for Sjögren's syndrome.     

Localization of antimicrobial peptides human β-defensins in minor salivary glands with Sjögren's syndrome

Sjögren's syndrome is a common systemic autoimmune disease associated with inflammatory cells that infiltrate exocrine glands. The antimicrobial peptides human β-defensin-1, human β-defensin-2, and human β-defensin-3 are expressed in various human epithelial cells and in normal salivary glands. Antimicrobial peptides provide local protection against infection and participate in inflammatory responses. Because of the presence of inflammation, we hypothesized that human β-defensin expression in minor salivary glands may be increased in subjects with Sjögren's syndrome. However, the expression of human β-defensins 1 and 2 was decreased in salivary glands affected by Sjögren's syndrome in comparison with the human β-defensin expression patterns in salivary glands from normal subjects. In addition, the reduction in expression of human β-defensin-2 was greater than the reduction in expression of human β-defensin-1. The aforementioned result suggests that the reduction in expression of human β-defensin-2 may occur earlier than the reduction in expression of human β-defensin-1, which may lead to a greater decrease in human β-defensin-2 than in human β-defensin-1 during disease progression.     

The level of cariogenic microlorganisms in patients with Sjögren's syndrome

Sixteen patients with caries-inacthe Sjögren's syndrome with low parotid salivary flow rates (≤ 0.25 mL/min) and 18 caries-inactive control subjects with higher salivary flow rates were compared. Mutans streptococci (MS) and lactobacilll (LB) counts were measured by means of Dentocult® SM strip mutans and LB assays. The group with Sjögren's syndrome displayed higher counts of MS (P = 0.014) and LB (p = 0.003) when compared with controls. The results of this study indicate that patients with caries-inactive Sjögren's syndrome and low salivary flow may have higher colonization of cariogenic mlcro-organisms than healthy individuals.     

Focal lymphocytic infiltration in the human labial salivary glands: a postmortem study

Focal lymphocytic infiltration in the human labial salivary glands was examined in a series of 190 postmortem subjects after suitable exclusion had been made. Focal lymphocytic infiltration, with or without a slight degree of parenchymal atrophic change, was found in 22.4% of the males and in 35.7% of the females. Of these, 9.0% (12 subjects) of the males and 10.7% (6 subjects) of the females with focal lymphocytic infiltration did not show any atrophic changes of the parenchyma. In the series reported here, the prevalence of focal lymphocytic infiltration apparently differs from the results of earlier investigators who had reported that none of the postmortem subjects without autoimmune diseases or connective tissue diseases showed focal lymphocytic infiltration in minor salivary glands. Although the pathological significance of focal lymphocytic infiltration in the minor salivary glands remains obscure, its diagnostic value for Sjögren's syndrome is discussed.     

The minor salivary gland proteome in Sjögren's syndrome

Objective:  To identify the global protein expression (the proteome) in the minor salivary glands from primary Sjögren's syndrome (pSS) patients and non-SS controls.
Materials and methods:  Minor labial salivary glands were obtained from six pSS patients and from six age-matched non-SS controls, lysed in SDS buffer and pooled into two groups, respectively. The lysates were analysed by liquid chromatography electrospray ionization combined with tandem mass spectrometry. Also, the proteins were separated by two-dimensional polyacrylamide gel electrophoresis and protein spots were subjected to mass spectrometry.
Results:  Heat shock proteins, mucins, carbonic anhydrases, enolase, vimentin and cyclophilin B were among the proteins identified. The differences in the proteomes of minor salivary glands from pSS patients and non-SS controls were mainly related to ribosomal proteins, immunity and stress. Alpha-defensin-1 and calmodulin were among six proteins exclusively identified in pSS patients.
Conclusion:  We have identified several minor salivary gland proteins that may have implications for clarifying the SS pathophysiology. This experiment adds to the knowledge of proteins produced in salivary glands in health and disease, and may form the basis of further studies on biomarkers of prognostic and diagnostic value.     

Minor salivary gland hyalinisation and amyloidosis in low-grade lymphoma of MALT

Two patients with low-grade lymphoma of mucosa-associated lymphoid tissue (MALT) arising in primary Sjögren's syndrome developed solitary nodules in their lips. Histologically both lesions showed enlargement and hyalinisation of single minor salivary glands with acinar atrophy, loss of most ducts and conversion into almost acellular sclerotic eosinophilic masses. In one case the lesion was shown to contain an amyloid component. No amyloid was detected in the second case but deposition of collagen and basement membrane and sclerotic neoplasm were excluded.     

Anti-salivary antibodies in primary Sjögren's syndrome

Earlier studies have described an antibody that recognized salivary ductal epithelium in sera from 15–50% of patients with primary Sjögren's syndrome; however, the specific salivary antigen in those studies was not identified. The present study further investigated this unknown salivary antigen. Twenty-nine of 31 patients (94%) with primary Sjögren's syndrome demonstrated IgG antinuclear antibodies that bound to an epithelial cell line with ductal characteristics derived from a human salivary gland. Seventy-seven percent of these patients had serum antibodies that bound to ductal cells of normal human parotid tissue after formalin fixation. Western blots of cell extracts, immunofluorescence, and adsorption studies indicated that SS-A/Ro and SS-B/La were the antigens recognized in the salivary cell line. The pattern of fluorescence seen when anti-SS-B/La bound to normal parotid tissue was identical to the fluorescence pattern of the anti-salivary ductal antibodies described in earlier literature.     

Oral pilocarpine HCl stimulates labial (minor) salivary gland flow in patients with Sjögren's syndrome

Pilocarpine HCl has been shown to stimulate parotid and submandibular gland salivary flow. The purpose of this study was to determine whether this cholinergic-muscarinic drug also stimulates labial (minor) salivary gland (LSG) flow and to relate that with whole unstimulated salivary (WUS) flow rateS. Subjects diagnosed with primary Sjögren's syndrome (SS-1; n = 9) or secondary Sjögren's syndrome (SS-2; n = 9) were enrolled in this study after meeting stringent enrollment criteria. An age-gender matched control group was also enrolled. The labial saliva was collected in a standardized manner on Per-iopaper® for 5 min and the volume was analysed by the Periotron®.Whole unstimulated salivary samples were collected for 5 min by the method of Mandel and Wot-man (1976).Each subject was dosed with pilocarpine HCl (5 mg; tablets; p.o.).After 60 min the LSG flow as well as the WUS flow was determined again as previously. The results indicated a significant (>180%) increase in both labial salivary gland flow as well as whole salivary flow in the SS-1 and SS-2 subjects (mean ± S. e.m.): [SS-1: WUS = 0.1080 ± 0.03 vs 0.2242 ± 0.03 ml per 5 min; LSG = 93.1 ± 22.2 vs 167.8 ± 15.9 μl/5 min; P < 0.001; SS-2: WUS = 0.1384 ± 0.02 vs 0.2775 ± 0.09 ml per 5 min; LSG = 97.7 ± 20.2 vs 182.8 ± 17.9 μl per 5 min; P < 0.001]. These results indicate a significant increase in labial salivary gland flow as well as whole salivary flow as stimulated by pilocarpine HCI in Sjögren's syndrome patients.     

Localization of lysozyme mRNA in the labial salivary glands by in situ hybridization in Sjögren's syndrome

Abstract – In this study, lysozyme mRNA in labial salivary glands has been localized with in situ hybridization technique using 35S-labeled hen lysozyme cDNA (cDNALZM) as a hybridization probe in normals and in patients with Sjögren's syndrome. 35S-DNALZM:mRNA hybrids were detected only in acinar serous cells, although lysozyme was identified in ductal cells using immunohistochemical techniques. Our results suggest that the serous acinar cells are the only site of lysozyme synthesis in small salivary glands. The presence of lysozyme in ductal cells may be a result of reabsorption from the saliva or concentration from the blood or surrounding tissues.     

Salivary gland scintigraphy with 99mTc-pertechnetate in Sjögren's syndrome: relationship to clinicopathologic features of salivary and lacrimal glands

Salivary gland scintigraphy was performed on 52 patients who were suspected of having Sjögren's syndrome (SS). and the results were compared with clinicopathologic features of the salivary and lacrimal glands. The time-activity curves which were obtained from computer-assisted analysis of ^99mTc-pertechnetate (^99mTc) scintigraphy were classified into four types (normal, median, flat and sloped types). The stimulated parotid flow rate decreased and the incidence of SS-related sialographic and histopathologic findings increased significantly as the scintigraphic abnormality advanced. In addition, the lacrimal gland function decreased and the proportion of patients diagnosed as having keratoconjunctivitis sicca (KCS) increased significantly as the scintigraphic abnormality advanced. These results indicate that the results of scintigraphy are related not only to the clinicopathologic features of the salivary glands but also to the lacrimal gland function in SS.     

Management of dry mouth in Sjögren's syndrome

The management of dry mouth is essential for patients with Sjögren's syndrome. The symptomatic treatment has included using air humidifiers, rinsing the mouth with water or mouthwash, the application of a salivary substitute and administration of secretagogues. There are three secretagogues suitable for the alleviation of dry mouth in Sjögren's syndrome patients in Japan; cevimeline hydrochloride hydrate (cevimeline), pilocarpine hydrochloride, and anetholtrithione. A relationship between the effect of cevimeline on saliva secretion and the degree of salivary gland destruction evaluated by sialography and histopathological findings in the labial minor salivary glands has been reported. These diagnostic approaches could provide useful prognostic information on the efficacy of cevimeline in Sjögren's syndrome patients. Concomitantly, a bite guard was suggested as an effective lubricating device because it maintains the lubricants in the proper location. In addition, the management of the complications of dry mouth, such as tooth caries, periodontitis and oral candidiasis, which all lead to a reduction in the QOL, is also important. Both the prevention and treatment of erythematous candidiasis is especially important in the management of Sjögren's syndrome.     

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?? Sjögren syndrome??SS??is classified as primary Sjögren syndrome??pSS??and secondary Sjögren syndrome??sSS??. It is an autoimmune exocrinopathy characterised by lymphocytic infiltration of exocrine glands in multiple sites??including both lacrimal and salivary glands??so the patients often suffer from dry mouth and dry eyes. Now the pathogeny and its pathogenesis is still  under study??and this review will elaborate from the aspects of cytokines??antibody??gene??virus and so on.     

Laser as a therapy for dry mouth symptoms in a patient with Sjögren's syndrome: a case report

This clinical case study reports on dry mouth symptoms in a patient with Sjögren's syndrome (SS) who was treated with laser phototherapy (LPT). A 60-year-old woman diagnosed with SS was referred to the laboratory for lasers in dentistry to treat her severe xerostomia. A diode laser (780 nm, 3.8 J/cm², 15 mW) was used to irradiate the parotid, submandibular, and sublingual glands, three times per week, for a period of 8 months. The salivary flow rate and xerostomia symptoms were measured before, during, and after LPT. Dry mouth symptoms improved during LPT. After LPT, the parotid salivary gland pain and swelling were no longer present. Treatment with LPT was an effective method to improve the quality of life of this patient with SS.     

Ultrastructural study of Sjögren's syndrome-like disease in MRM mice

Salivary glands of autoimmune MRL/1 mice were examined ultrastructurally and by immunoelectron microscopy to further characterize the Sjögren's syndrome-like disease in these animals. Major salivary glands from 12 female and 7 male MRL/1, two female MRL/n, and one female BALB/c mice were examined by electron microscopy and the glands from 4 female MRL/1 mice were subjected to immunoelectron microscopy in order to detect Lyt-1 and Lyt-2 positive lymphoid cells. Mononuclear cell infiltrates were not seen in the salivary gland from the BALE mouse and occurred rarely in glands of MRL/n mice. However, in MRL/1 mice, numerous lymphoid cells were present and acinar cells displayed low cytoplasmic density, cytoplasmic vacuolization and cellular lysis. Lymphoid cells were predominantly Lyt-1 positive although some Lyt-2 positive cells were observed. These results suggest that the MRL/1 mouse represents a useful model for the study of the pathogenesis of Sjogren's syndrome in man.     

An association between salivary gland disease and serological abnormalities in Sjögren's syndrome

In the labial salivary glands (LSGs) of 16 primary and 18 secondary Sjögren's syndrome (SS) patients, infiltrating lymphocytes were histologically and immunohistochemically examined: also, the serum levels of rheumatoid factor, antinuclear antibodies, anti-DNA antibodies, anti-SS-A and anti-SS-B antibodies, and immunoglobulins (including IgG, IgM and IgA) were all assayed. An immunohistochemical analysis of the lymphocyte subsets in LSGs revealed that severe lymphocytic infiltration was frequently accompanied by marked B cell accumulation both in primary and secondary SS patients. Furthermore, local B cell accumulation was also closely associated with elevated levels of anti-SS-A and anti-SS-B antibodies and IgG, and this association was statistically significant in the group with primary SS but not in the group with secondary SS. Thus, local lymphocytic infiltration, especially B cell accumulation, in the salivary glands is suggested to be involved in serological abnormalities in primary SS. while complicated autoimmune diseases other than SS may also be involved in serological abnormalities in secondary SS.     

Clinical utilization of sialochemistry in Sjögren's syndrome

Sialochemistry was performed on the stimulated parotid secretion of a group of patients with Sjögren's syndrome (SS) having a Grade 4 iymphocytic infiltrate of their minor labial salivary glands and a normal control group. Parameters examined included flow rate, and concentration of sodium, potassium, chloride, urea, calcium, phosphate, total protein, IgA, IgG. albumin, amylase and lactoferrin. Although all SS patients had virtually no parotid secretion in the absence of stimulation, with a gustatory stimulation, 40% of the patients with SS had a relatively normal parotid flow rate, when compared with the control group. The SS patients, regardless of flow rate, exhibited a highly significant (p < 0.01) elevation in the concentration of sodium, chloride, IgA, IgG, and lactoferrin and a significant (p < 0.05) increase in albumin concentration, when compared with the control group. The phosphate level was significantly lower (p < 0.01) in SS patients than in the control group. The elevated IgA in SS was almost all 1 IS, in contrast to parotitis where 7S was a major contributor. In view of the variation in flow rate in SS patients chemical quantitation of selected salivary components can be a valuable aid in the differential diagnosis of this disease and in monitoring patients over time.