Sjögren's Syndrome Group Research Articles

Cardiovascular risk factors in women with primary Sjögren's syndrome: United Kingdom primary Sjögren's syndrome registry results.

ObjectiveTo determine the prevalence of traditional cardiovascular risk factors using established definitions in a large cohort of clinically well-characterized primary Sjögren's syndrome (SS) patients and to compare them to healthy controls.MethodsData on cardiovascular risk factors in primary SS patients and controls were collected prospectively using a standardized pro forma. Cardiovascular risk factors were defined according to established definitions. The prevalence of cardiovascular risk factors in the primary SS group was determined and compared to that in the control group.ResultsPrimary SS patients had a higher prevalence of hypertension (28–50% versus 15.5–25.6%; P < 0.01) and hypertriglyceridemia (21% versus 9.5%; P = 0.002) than age- and sex-matched healthy controls. Furthermore, a significant percentage (56%) of hypertensive patients expected to be on antihypertensive treatment according to best practice was not receiving it.ConclusionPrimary SS patients are more than 2 times more likely to experience hypertension and hypertriglyceridemia than age- and sex-matched healthy controls. Additionally, hypertension is underdiagnosed and suboptimally treated in primary SS.

Elevated IgG4 serum levels among primary Sjögren's syndrome patients: do they unmask underlying IgG4-related disease?

To determine IgG4 levels in a cohort of consecutive patients with primary Sjögren's syndrome (SS) and other autoimmune diseases and explore whether they associate with distinct clinical, serologic, and histopathologic features. Serum IgG4 levels were measured in 133 primary SS patients and 49 healthy donors (HDs). Seventy-four lupus and 54 rheumatoid arthritis (RA) patients served as disease controls. Immunohistochemical IgG4 analysis was performed in paraffin-embedded minor salivary gland (MSG) tissues. Raised IgG4 serum levels (>135 mg/dl) were detected in 10 (7.5%) of 133 primary SS patients (high-IgG4 group), in 8 (10.8%) of 74 lupus patients, in 7 (12.9%) of 54 RA patients, and in 1 (2%) of 49 HDs. Compared to the normal-IgG4 (<135 mg/dl) primary SS group, high-IgG4 patients exhibited increased prevalence of IgG4-related features (autoimmune cholangitis, autoimmune pancreatitis, and interstitial nephritis), lower rates of antinuclear antibody positivity, and higher IgG2 and IgE levels. Positive staining for IgG4+ plasma cells with an IgG4:IgG ratio ≥40% was detected in 3 of 6 available MSG tissues in the high-IgG4 group. Criteria of possible or definite IgG4-related disease (IgG4-RD) were fulfilled by 10 (7.5%) of 133 of our primary SS cohort. Raised IgG4 serum levels were detected in 7.5% of primary SS patients in association with IgG4RD-reminiscent clinical, serologic, and histopathologic features. Whether this high-IgG4 primary SS group represents a misclassified IgG4-RD group or a distinct primary SS subtype remains to be further explored in future studies.

Serum nerve grow factor and brain-derived neurotrophic factor profiles in Sjögren’s syndrome concomitant with interstitial lung disease

The aim of this study is to investigate the serum levels and clinical significance of nerve grow factor (NGF) and brain-derived neurotrophic factor (BDNF) in Sjogren's syndrome (SS) with interstitial lung disease (ILD). Fifty two untreated patients with SS were enrolled in the study. Of them, 25 patients only displayed salivary glands damage and/or lacrimal gland injury (simple SS group). The other 27 patients were lacrimal and/or salivary gland involvement as well as being concomitant only with intestinal lung disease (ILD group). Twenty-five serum samples from healthy volunteers were examined as controls. We measure serum NGF and BDNF levels by ELISA and correlate them with clinical data. Serum NGF levels were significantly higher in ILD patients (372 ± 129pg/ml) and simple SS patients (293 ± 72pg/ml) when compared with healthy controls (187 ± 47pg/ml) (both p < 0.01). Significant difference were also found between the two patient groups (p < 0.01). In contrast, BDNF were significantly decreased in ILD patients (1,005 ± 143pg/ml) when compared with either simple SS patients (1,204 ± 176pg/ml, p < 0.01) or healthy controls (1,217 ± 155pg/ml, p < 0.01). Correlation analysis showed NGF levels in ILD patient were positively correlated with serum levels of C-reactive protein and IgG (both p < 0.05). The abnormal NGF and BDNF in sera may be a potential character of ILD secondary to pSS.

Quantification of Conjunctival TNF-α in Aqueous-Deficient Dry Eye

This study aimed to quantify and compare conjunctival epithelial tumor necrosis factor (NF) α mRNA expression in Sjögren syndrome (SS), non-Sjögren syndrome aqueous-deficient dry eye (non-SS DE), and non-dry eye (NDE) control subjects. A total of 76 subjects were recruited for this study: 25 SS (confirmed via American-European Consensus Criteria 2002), 25 non-SS DE (confirmed by symptoms and Schirmer scores ≤ 10 mm), and 26 NDE. Superior and temporal bulbar conjunctival epithelial cells were collected via impression cytology. Epithelial RNA was extracted, and TNF-α mRNA expression was quantified by real-time quantitative polymerase chain reaction. The expression of TNF-α mRNA was found to be significantly higher in the SS group (2.48 ± 1.79) compared to both non-SS DE (0.95 ± 1.18; p < 0.05) and NDE (0.84 ± 0.51; p < 0.05) groups. No difference in TNF-α mRNA expression was found between the non-SS DE and NDE groups (p = 0.67). These results demonstrate that SS-associated aqueous-deficient dry eye is associated with a significant upregulation of conjunctival epithelial TNF-α mRNA relative to both non-SS DE and control groups. The degree to which TNF-α mRNA is upregulated in SS may contribute to the severe ocular surface damage observed in these patients.

Residual salivary secretion ability may be a useful marker for differential diagnosis in autoimmune diseases.

Background. We have elucidated decreased resting salivary flow in approximately 60% of patients with autoimmune diseases not complicated by Sjögren syndrome (SjS). In this study, salivary stimulation tests using capsaicin were performed to examine residual salivary secretion ability in patients with autoimmune diseases. Materials and Methods. Fifty-eight patients were divided into three groups: patients with primary or secondary SjS (SjS group), patients with systemic sclerosis not complicated by SjS (SSc group), and patients with other autoimmune diseases (non-SjS/non-SSc group). Simple filter paper and filter paper containing capsaicin were used to evaluate salivary flow rates. Results. Resting salivary flow rates were significantly lower in the SjS and SSc groups than in the non-SjS/non-SSc group but did not differ significantly between the SjS and SSc groups. Capsaicin-stimulated salivary flow rates were significantly lower in the SjS and SSc groups than in the non-SjS/non-SSc group, but not significantly different between the SjS and SSc groups. In the non-SjS/non-SSc group, salivary flow rates increased after capsaicin stimulation to the threshold level for determination of salivary gland dysfunction, whereas no improvement was observed in the SjS and SSc groups. Conclusion. Residual salivary secretion ability may be a useful marker for differential diagnosis in autoimmune diseases.

Analysis of Tear Cytokines and Clinical Correlations in Sjögren Syndrome Dry Eye Patients and Non–Sjögren Syndrome Dry Eye Patients

To compare concentrations of tear cytokines in 3 groups composed of Sjögren syndrome (SS) dry eye, non-Sjögren syndrome (non-SS) dry eye, and normal subjects. Correlations between ocular surface parameters and tear cytokines were also investigated. Prospective cross-sectional study. SS dry eye patients (n = 24; 40 eyes) were diagnosed with primary SS according to the criteria set by the American-European Consensus Group. Non-SS dry eye patients (n = 25; 40 eyes) and normal subjects (n = 21; 35 eyes) were also enrolled. Tear concentrations of interleukin (IL)-17, IL-6, IL-10, IL-4, IL-2, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α) were measured by a multiplex immunobead assay. Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), Schirmer I test, and fluorescein staining scores were obtained from dry eye patients. All cytokine levels except for IL-2 were highest in the SS group, followed by non-SS dry eye group and control subjects. Concentrations of IL-17, TNF-α, and IL-6 were significantly different among the 3 groups (IL-17: SS > control P < .001, non-SS > control P = .042, SS > non-SS P < .001; TNF-α: SS > control P = .006, non-SS > control P = .034, SS > non-SS P = .029; IL-6: SS > control P = .002, non-SS > control P = .032, SS > non-SS P = .002). IL-17 was significantly correlated with TBUT (R = -0.22, P = .012) and Schirmer I test (R = -0.36, P = .027) scores in the SS group. IL-6 was significantly correlated only with TBUT (R = -0.38, P = .02) in the non-SS group. Differences in tear cytokine levels and correlation patterns between SS dry eye and non-SS dry eye patients suggest the involvement of different inflammatory processes as causes of dry eye syndrome.

Elevated Immunoglobulin to Tissue KLK11 in Patients With Sjögren Syndrome

We have previously reported that mouse kallikrein (KLK) 22 in the lacrimal and salivary glands is an autoantigen that can induce primary Sjogren syndrome (SS) in rats. In this study, we determine whether the production of antibodies against tissue KLK is specific for SS and whether the antibody can be used as a biomarker for the diagnosis in humans. Sera from 11 patients diagnosed with SS, 8 patients with dry eye disease (DED), and 8 normal age/sex-matched controls (NL) were collected for detecting antibodies against tissue KLK1, KLK11, KLK12, and KLK13 by capture enzyme-linked immunosorbent assay. Anti-KLK11 antibody was significantly higher in the SS than in the DED (P = 0.05) and NL (P < 0.01) groups, with no difference in the level of this antibody between the DED and NL groups. In addition, receiver operating characteristic analysis revealed that, at or above an optical density cutoff point of 0.2695, anti-KLK11 antibody has a sensitivity of 82% and a specificity of 94% to distinguish the SS group from the other groups. Our results suggest that anti-KLK11 might be a novel biomarker for SS in humans. Further investigation is required to confirm this finding and to establish the exact role of KLK11 in the pathogenesis of SS.

Correlation between ultrasound imaging of major salivary glands and histopathological findings of labial gland biopsy samples in Sjogren's syndrome

BackgroundUltrasound imaging has been recognised as a non-invasive, reproducible method for assessing the major salivary glands. The aim of this study was to investigate the relation between ultrasound imaging of major glands and focal lymphocytic score (FS) of minor salivary glands in Sjogren's syndrome. MethodsBiopsies of labial glands and ultrasound imaging of major glands were done on 196 patients (mean age 55 years, 19 male, 177 female) attending the Sjogren's Clinic at Guy's Hospital. FS of labial glands was judged by two histopathologists whose assessment was standardised. Ultrasonography was done with a single Philips-iU22 Ultrasound machine, and a disease severity score (US) was determined. Patients were categorised into three groups: those diagnosed with Sjogren's syndrome according to the American-European classification criteria (Sjogren's syndrome group), those with non-specific sialadenitis (sialadenitis group), and those with normal biopsy results (non-salivary gland disease group). FindingsThere was a highly significant correlation between FS and US scores (mean score 1·8 [SD 2·4, range 0–11·3] vs 2·7 [2·9, 0–9], r=0·665, n=196; p<0·0001). Mean FS and US scores for the Sjogren's syndrome group were significantly greater than for the sialadenitis group (p=0·0001). For the Sjogren's syndrome group, there was a significant correlation between FS and US scores (mean score 3·6 [SD 2·6, range 0–11·3] vs 5·0 [2·4, 0–9], r=0·395, n=87; p<0·0001). For the sialadenitis group, there was a significant correlation between FS and US scores (mean score 0·4 [SD 0·6, range 0–2·3] vs 1·1 [1·7, 0–7], r=0·321, n=66; p<0·005). No obvious correlation between FS and US scores existed for the non-salivary gland disease group (mean score 0·2 [SD 0·5, range 0–2·6] vs 0·5 [SD 1·2, 0–5], n=43). InterpretationThis is the first large-scale study to show the strong relation between US scores of major salivary glands, and FS scores of minor salivary glands, suggesting a uniform disease process. Ultrasound analysis proves to be an important methodology in management and studies of Sjogren's syndrome. FundingNational Institute for Health Research.

Sialochemistry and cortisol levels in patients with Sjogren’s syndrome

(i) To determine whether salivary cortisol and electrolyte levels differ between patients with Sjogren's syndrome (SjS) and healthy individuals. (ii) To assess correlations between whole-saliva cortisol and some clinical manifestations in patients with SjS. A total of 24 healthy women (mean age 49.3±9.8) served as controls (C) vis-à-vis 17 patients with SjS (mean age 55.5±15.7). Salivary cortisol concentration was determined, and sialochemistry analysis was performed. Significantly lower saliva flow rates and higher salivary chloride (Cl(-) ), potassium (K(+) ), and Ca(2+) levels were found in the SjS group. No significant differences or correlations were found in other parameters, including sodium (Na(+) ), magnesium (Mg(2+) ), phosphate ((-) ), urea (U), and salivary cortisol levels. Increased whole-salivary output of Cl(-) and K(+) in SjS may reflect release from apoptotic rests of acinar cells after secondary necrosis. Normal levels of salivary Na(+) , Mg(2+) , and (-) argue against concentration effect, deranged tubular function or cortisol (mineralocorticosteroid) effect as the cause for these findings. Increased salivary Ca(2+) levels probably reflect leakage of plasma Ca(2+) through the injured oral mucosa in SjS. In spite of disease-associated stress, salivary cortisol, a stress biomarker, was not increased, suggesting insufficient hypothalamus-pituitary-adrenal (HPA) axis response and/or local consumption of cortisol by lymphocyte infiltrates.

Effects of Reduced Saliva Production on Swallowing in Patients with Sjogren’s Syndrome

This study aimed to further characterize the nature of swallowing dysfunction in patients with Sjogren's syndrome (SS). Subjects filled out a perception of swallow function form. Measures of stimulated salivary flow rate were also taken, and videofluoroscopic evaluation of swallowing was completed. The amount of saliva produced by patients with SS was significantly less than that produced by normal age-matched controls, and these patients perceived their swallowing to be impaired. Few statistically significant differences were found between the SS group and normal age-matched controls on temporal measures of swallowing, and 96% of swallows in the SS group were judged to be functional. There was no correlation between perception of swallowing and amount of saliva produced. No strong correlations were found between temporal measures of swallowing and salivary flow rate. Results indicated that patients with SS tend to perceive their swallowing to be worse than physiologic swallowing measures indicate. The decreased saliva production in these patients does not appear to be the cause of their perceived swallowing difficulty but may affect their sensory judgment of swallow function. Future studies will focus on how quality of saliva affects swallowing in these patients.

Quantitative and visual evaluation of salivary and thyroid glands in patients with primary Sjögren's syndrome using salivary gland scintigraphy: relationship with clinicopathological features of salivary, lacrimal and thyroid glands

To evaluate quantitative and visual salivary gland scintigraphy in patients with primary Sjögren's syndrome (SS) and to compare the scintigraphic findings with clinicopathological features of the salivary, lacrimal and thyroid glands. Twenty-seven patients with primary SS and 10 healthy age-matched and sex-matched individuals as a control group were included in this study. The diagnosis of SS was made on the basis of the classification criteria of the American-European Consensus Group. The patients with primary SS were divided into two groups as early-stage and advanced-stage according the labial biposy scores (16 early-stage and 11 advanced-stage). After the administration of 370 MBq Tc-99m pertechnetate, static images were obtained at 20 min and also after lemon stimulation. Functional parameters for the parotid, submandibular, and thyroid glands were calculated. Schirmer-I, tear film break-up time and Rose Bengal tests were evaluated. Statistically significant differences existed for the functional parameters of the parotid and submandibular glands between the early-stage and advanced-stage groups. The submandibular glands were more frequently affected than the parotid glands. Asymmetric uptake pattern was more common in the parotid glands during the early-stages of primary SS. When compared with the control group, the thyroid uptake ratio of the early-stage primary SS and advanced-stage group was not significantly different. According to the results of the ophthalmological tests, there was a statistically significant difference between patients with advanced-stage and early-stage disease. There were no significant correlations between functional parameters of salivary gland and any of the ophthalmological tests. The results indicate that quantitative salivary gland scintigraphy may be a useful method for evaluating salivary gland dysfunction and also for determining disease severity in primary SS. Asymmetric activity pattern in the parotid glands commonly observed during the early stages of the disease may be a predictor of progression. In addition, the histopathological stage is related not only to the scintigraphic findings of the salivary glands but also to lacrimal gland function in primary SS. However, thyroid uptake seemed to be unaffected in patients with both early-stage and advanced-stage disease.

Evaluation of Therapeutic Effects of Astaxanthin on Impairments in Salivary Secretion

The involvement of reactive oxygen species (ROS) in the pathophysiology of Sjögren’s syndrome (SS), an autoimmune disorder, and irradiation-induced impairments in salivary secretion has been reported. Meanwhile, the strong antioxidant astaxanthin (Ast) has been suggested to have therapeutic effects on various diseases. In the present study, we examined the ROS scavenging capacity of Ast using a human salivary gland epithelial cell line (HSY) and investigated the effects of Ast on salivary secretion in a mouse model of irradiation-induced salivary gland dysfunction. Furthermore, we performed a clinical study of Ast in six SS patients and six normal individuals, quantifying the volume of saliva secretion and the level of oxidative stress markers in the saliva. Ast partially suppressed hydrogen peroxide-induced ROS in HSY cells. The mouse model demonstrated that the pre-administration of Ast resulted in the suppression of irradiation-induced hyposalivation. Furthermore, the administration of Ast appeared to increase salivary output in both the SS and normal groups. The level of oxidative stress marker, hexanoyl-lysine, in the saliva was reduced after Ast intake. These results suggest that Ast might act as an ROS scavenger, providing benefits to SS patients with impaired salivary secretion.

Quality of life in patients with Sjögren’s syndrome and sicca complex

To investigate the general and oral quality of life in patients with Sjögren's syndrome (SS) and sicca complex. Forty-four patients with SS were studied consecutively, 33 were primary SS and 11 secondary SS, classified in accordance with the Vitali European criteria. The Spanish version of the Medical Outcome Short Form (36) Health Survey questionnaire (SF-36) was used to evaluate general quality of life and the Oral Health Impact Profile (OHIP-49) Spanish version to study oral quality of life. Regarding general quality of life using the SF-36, when comparing the SS and the control groups, lower scores were obtained in the SS groups in all domains and on comparing primary and secondary SS, lower scores were found for primary SS in all the subscales. With respect to oral quality of life using the OHIP-49 (all items), we found lower scores for the primary SS group with respect to the control group. Patients with primary SS present lower scores for both oral and general quality of life.

Tear Lipocalin and Lysozyme in Sjögren and Non-Sjogren Dry Eye

To evaluate the concentration of tear lipocalin, lysozyme, and total protein in Sjögren's Syndrome (SS), non-Sjögren's keratoconjunctivitis sicca (KCS), and non-dry-eyed (NDE) individuals. Seventy-six subjects were recruited for this study: 25 SS subjects; 25 KCS subjects, and 26 NDE individuals. Symptoms were measured with a visual analogue scale. Tear flow was measured by the Schirmer I test without anesthesia. Tears were collected using an eye wash technique. Total tear protein was quantified using the DC Protein Assay Kit. Tear lipocalin and lysozyme were quantified via Western blotting performed on a Phast System. By definition, the SS and KCS groups both had significantly lower mean Schirmer scores (5.12 +/- 5.96 mm and 7.84 +/- 7.35 mm) compared with the NDE group (23.83 +/- 7.85 mm; p < 0.0001). There was no difference in mean Schirmer scores between SS and KCS groups (p = 0.19). The tear film of the SS group was characterized by significantly reduced (p < 0.0001) total protein and lipocalin concentrations compared with both KCS and NDE groups. No difference between the KCS and NDE groups was found in total protein (p = 0.92) or lipocalin (p = 0.19) concentration. In contrast, the concentration of tear film lysozyme was found to be statistically similar in all three groups examined. No statistically significant correlation was found in any group between mean Schirmer values compared with total protein, lipocalin or lysozyme concentration. Our data demonstrate a biochemical distinction between the Sjögren's group compared with both KCS and control groups, in that both tear lipocalin and total tear protein were significantly reduced. Although correlations were not found between protein measurements and tear flow, a combination of tests including Schirmer I and quantitation of tear film biomarkers may allow for the identification of SS patients without the need for invasive testing.

Clinical and laboratory profiles of systemic lupus erythematosus associated with Sjögren syndrome in China: a study of 542 patients

This study aims to investigate the clinical and laboratory features of systemic lupus erythematosus (SLE) patients associated with Sjögren syndrome (SS) in China, as well as its similarities to and differences from SLE patients without SS. A group of 542 consecutive unselected SLE patients was recruited. Diagnosis of SLE was made according to 1997 revised American College of Rheumatology SLE criteria; SS was diagnosed using the American-European classification criteria. Clinical and laboratory parameters in SLE patients with SS (SLE-SS) were compared with those in SLE patients without SS (SLE-no SS). Overall, SS was identified in 35 SLE patients (6.5%); the onset of SS preceded the development of SLE in 17 of them (48.6%). Compared with the SLE-no SS group (35.8 +/- 10.5 years), patients with SLE-SS (41.3 +/- 11.6 years) were significantly older (P = 0.003), had a higher frequency of anti-Ro/SSA, anti-La/SSB, and anti-dsDNA antibodies, but had a significantly lower frequency of renal involvement. This study demonstrates that SLE-SS may be a subgroup of patients with characteristic clinical and laboratory features. To improve the treatment outcomes in SLE-SS patients, more specific treatment should be applied based on those factors.

Quantitative analyses of sonographic images of the parotid gland in patients with Sjögren’s syndrome

The first purpose of this study was to quantify the sonographic images of the salivary gland to differentiate the Sjögren syndrome (SS) group from the non-SS group. We included 132 patients in this study who had been referred to our department because of a suspicion of SS. A total of 91 patients fulfilled the criteria for SS, whereas the remaining 41 patients did not. We placed the regions-of-interest within the lesion. The first purpose was to evaluate which indices obtained by the texture analyses were useful for differentiating the SS group from the non-SS group. The second purpose was to evaluate the relationship between the indices and the degree of severity in the SS group. Out of the several indices evaluated, Hurst coefficients, obtained by fractal analysis, of SS group were found to be significantly lower than those of the non-SS group. Moreover, the Hurst coefficient was associated with the degree of destruction of the parotid gland as assessed by sialography. The Hurst coefficient of a globular stage and an advanced stage were both significantly lower than that of a normal pattern, whereas the Hurst coefficient of a punctate stage was almost similar to that of the normal stage. The Hurst coefficient showed a very weak correlation with the results of either the gum test or serologic tests. (E-mail: chikui@rad.dent.kyushu-u.ac.jp)

Identification of parotid salivary biomarkers in Sjögren's syndrome by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and two-dimensional difference gel electrophoresis

To identify the most significant salivary biomarkers in Sjögren's syndrome (SS) using proteomic methods. Parotid saliva from 20 non-SS subjects and 41 primary SS patients was analysed. Protein expression profiles for each sample were generated by surface-enhanced laser desorption/ionization time-of-flight-mass spectrometry (SELDI-TOF-MS). Mean peak intensities of SS patients and non-SS subjects were compared by univariate analyses. Samples pooled by diagnosis (SS and non-SS) and labelled with different Cy dyes were compared by two-dimensional difference gel electrophoresis (2D-DIGE). Two protein levels that were most significantly different by SELDI-TOF-MS and 2D-DIGE were validated by enzyme-linked immunosorbent assay in individual samples. SELDI-TOF-MS of 10-200 kDa peaks revealed eight peaks with >2-fold changes in the SS group that differed from non-SS at P < 0.005. Peaks of 11.8, 12.0, 14.3, 80.6 and 83.7 kDa were increased, while 17.3, 25.4, and 35.4 kDa peaks were decreased in SS samples. 2D-DIGE identified significant increases of beta-2-microglobulin, lactoferrin, immunoglobulin (Ig) kappa light chain, polymeric Ig receptor, lysozyme C and cystatin C in all stages of SS. Two presumed proline-rich proteins, amylase and carbonic anhydrase VI, were reduced in the patient group. Three of these ten biomarkers have not been associated previously with SS. The salivary proteomic profile of SS is a mixture of increased inflammatory proteins and decreased acinar proteins when compared with non-SS. Future studies will test the ability of these biomarker levels, alone and in combination, to diagnose the salivary component of SS.

Prevalence of IgG Anti‐α‐Fodrin Antibodies in Sjögren's Syndrome

The objective of this study was to determine the prevalence of antibodies against alpha-fodrin (alpha-fodrin) of the immunoglobulin G (IgG) isotype in Sjögren's syndrome (SS), as defined by European Community Study Group (ESG) and ESG-modified criteria. We arrived at the prevalence and mean concentrations of IgG anti-alpha-fodrin antibodies using enzyme-linked immunosorbent assay (ELISA) in 507 patients with SS, primary SS (pSS), and secondary SS (sSS), classified according to either the ESG or the ESG-modified criteria. IgG anti-alpha-fodrin antibodies were detected in 6/507 (1.2%) and 4/228 (1.7%) of the SS group, according to the ESG or ESG-modified criteria, respectively. Similar prevalence was found for patients with pSS or sSS. Anti-Ro/SSA antibodies were present in 151/409 (36.9%) vs. 149/213 (70.0%) of the SS group, 85/195 (43.6%) vs. 83/101 (82.2%) of the pSS group, and 66/214 (30.8%) vs. 66/112 (58.9%) of the sSS group. Anti-La/SSB antibodies were detected in 77/403 (19.1%) vs. 73/212 (34.4%) of the SS group, 47/194 (24.2%) vs. 45/101 (44.5%) of the pSS group, and 30/209 (14.3%) vs. 28/111 (25.2%) of the sSS group. No clinical associations were found. Only two IgG anti-alpha-fodrin-positive sera were anti-Ro/SSA-negative. We conclude that IgG antibodies against alpha-fodrin are present in a small percentage of people with SS, pSS, and sSS. The lower prevalence in patients classified according to the ESG criteria reflects the lower specificity of these criteria. IgG anti-alpha-fodrin antibodies can be detected in some SS patients whose sera do not contain anti-Ro/SSA antibodies.

Effect of Cevimeline on Salivary Components in Patients with Sjögren Syndrome

The aim of this study is to clarify the effects of cevimeline on various components in human saliva, such as immunoglobulin A (IgA), lysozyme, α-amylase and squamous cell carcinoma (SCC) antigen. Twelve female patients with Sjögren syndrome (SS) and 14 healthy women were enrolled. After the first saliva collection, one capsule (30 mg) of cevimeline was administered to each subject. Saliva was collected again after 90 min. The salivary flow rate and concentration of each component were measured. In both groups the salivary flow rate and amylase concentration were significantly increased by cevimeline. The lysozyme and IgA concentrations did not change significantly in both groups. The SCC antigen concentration did not change significantly in the SS group, but it decreased significantly in the control group. The secretion rates of amylase and IgA showed significant increases in both groups. The secretion rate of lysozyme significantly increased only in the control group, while the secretion rate of SCC significantly increased only in the SS group. Cevimeline augments not only the salivary flow rate but also the secretion rate of some digestive and/or defense factors from infections. It may be beneficial for SS patients to continue taking cevimeline to prevent oral infections, and other serious sequelae.

Gene expression profiling of minor salivary glands clearly distinguishes primary Sjögren's syndrome patients from healthy control subjects

To identify gene expression signatures in minor salivary glands (MSGs) from patients with primary Sjogren's syndrome (SS). A 16K complementary DNA microarray was used to generate gene expression profiles in MSGs obtained from 10 patients with primary SS and 10 control subjects. The data were analyzed by 2 different strategies, one strict primary analysis and one subanalysis that allowed for inclusion of genes with no signal in more than 3 samples from each group. The results were validated by quantitative reverse transcriptase-polymerase chain reaction techniques. We found a distinct difference in gene expression levels in MSGs, enabling a simple class prediction method to correctly classify 19 of the 20 samples as either patient or control, based on the top 5 differentially expressed genes. The 50 most differentially expressed genes in the primary SS group compared with the control group were all up-regulated, and a clear pattern of genes involved in chronic inflammation was found. CXCL13 and CD3D were expressed in >/=90% of primary SS patients and in </=10% of the controls. Lymphotoxin beta, as well as a number of major histocompatibility complex genes, cytokines, and lymphocyte activation factors, manifested its role in the pathogenesis of SS. Numerous type I interferon genes related to virus infection were found among the top 200 genes, with increased expression in primary SS. Interestingly, the expression of carbonic anhydrase II, which is essential in saliva production and secretion, and the apoptosis regulator Bcl-2-like 2 were down-regulated in primary SS patients. We have identified distinct gene expression profiles in MSGs from patients with primary SS that provide new knowledge about groups of genes that are up-regulated or down-regulated during disease, constituting an excellent platform for forthcoming functional studies.