Primary Sjögren's Syndrome Patients Research Articles

Chemokine tear levels in primary Sjögren's syndrome and their relationship with symptoms.

To evaluate CCL2, CXCL8, and CXCL10 in the tears of patients with Primary Sjögren's syndrome (PSS) and correlate them with ocular symptoms/discomfort and objective ocular tests. We studied 21 patients with PSS. A single ophthalmologist, expert in dry eye, examined the patients and assessed tear film breakup time, Schirmer I test, tear meniscus height, Van Bijsterveld staining score and SICCA Ocular Staining Score. We also assessed the ESSPRI and ocular dryness VAS and the Ocular Surface Disease Index (OSDI), a 12-item scale assessing symptoms associated with dry eye disease and their impact on vision (ocular symptoms/discomfort). Tear samples collected with sterile tear flow strips were frozen at -86°C until testing. After thawing, tears were extracted from the strips. We tested CCL2, CXCL8, and CXCL10 by luminometry. We also included 21 healthy control subjects without a dry eye. CXCL8 levels were similar in patients and controls. PSS patients had lower levels of CXCL10 (472.8 vs. 1652pg/μL, p = 0.009) and CCL2 (1.08 vs. 9pg/μL, p = 0.0001) than controls. Patients with worse ocular sicca symptoms/discomfort had the lowest CXCL10 levels (239.3 vs. 646.2pg/μL, p = 0.02). CCL2 correlated with tear meniscus height (τ = 0.37, p = 0.02) and with OSS (τ = -0.3, p = 0.05). We found lower levels of CXCL10 and CCL2 in the tears of patients with PSS, associating the former with worse ocular symptoms and the latter with positive ocular target tests.

The respiratory manifestations in patients with primary Sjögren's syndrome: is interstitial lung disease related to disease activity?

Sjögren's syndrome is a systemic, autoimmune disease and can affect many organs and systems. In this study, we aimed to evaluate the respiratory manifestations, and the association between interstitial lung disease (ILD) and disease activity in primary SS (pSS) patients. The study design was retrospective cross-sectional, and 151 patients followed up with a diagnosis of pSS between 2004 and 2019 were included in the study. Demographic and clinical data, laboratory results, chest radiographs and thorax computed tomography (CT) results were obtained from patient files and hospital imaging system. Thorax CT was requested from all patients with respiratory complaints and abnormalities in physical examination and pulmonary function test. Disease activity was calculated with EULAR pSS disease activity index (ESSDAI) and clinical European League Against Rheumatism SS Disease Activity Index (clin-ESSDAI). In our study, 97% of pSS patients were female, and the mean age was 55.9 ± 12 years, disease onset age was 45.5 ± 12.1 years, disease duration was 10.7 (1-38) years. According to CT findings of 120 patients, 35% had nodules, and 13.3% had ILD (62.5% nonspecific interstitial pneumonia, 25% lymphocytic interstitial pneumonia, 12.5% usual interstitial pneumonia). Bronchiectasis, emphysema, sequelae fibrotic changes, and pleural thickening was found in 3.3%, 5.8%, 15.8%, and 1.7% of patients, respectively. It was observed that there was a significant relationship between the presence of ILD and persistent cough, mediastinal LAP, low DLCO, high ESSDAI and clin-ESSDAI scores reflecting disease activity. The most common pulmonary manifestation in our patients was ILD. ILD was observed more frequently in patients with moderate and severe disease activity. Some of the ILD patients were diagnosed while they were asymptomatic. Even if they are asymptomatic, it is important to follow up the patients with physical examination, spirometry, DLCO and thorax CT.

Evaluation of retinal microvascular structures by optical coherence tomography angiography in primary Sjögren's syndrome.

There are insufficient data in the literature on how retinal capillaries are affected in primary Sjögren's syndrome (PSS). The aim of this study was to evaluate the retinal capillary density (CD) in PSS using optical coherence tomography angiography (OCTA). In this case-control study, 26 eyes from 13 PSS patients and 39 eyes from 20 healthy controls (HCs) were included. The CD in the regions of the superior capillary plexus (SCP), deep capillary plexus (DCP) and radial peripapillary capillaries (RPC) as well as assessment parameters of the foveal avascular zone (FAZ) were examined by OCTA. The mean CD (%) was 50.2 ± 4.2 and 50.5 ± 3.4 in the SCP (p = 0.904), 49.2 ± 7.5 and 53.9 ± 5.7 in the DCP (p = 0.006) and 50.8 ± 2.1 and 49.8 ± 2.2 in the RPC (p = 0.088) regions in patients with PSS and HCs, respectively. In patients with PSS and HCs, the mean sizes of the FAZ were 0.243 ± 0.07mm2 and 0.283 ± 0.13mm2 (p = 0.142), and the mean sizes of the non-flow area were 0.480 ± 0.11mm2 and 0.509 ± 0.13mm2, respectively (p = 0.359). The correlation coefficients (Rho) of retinal CD in the SCP, DCP and RPC regions with disease duration were - 0.545 (p = 0.004), - 0.389 (p = 0.050) and - 0.795 (p < 0.001), respectively. The retinal CD in PSS is lower than that in the healthy population in deep retinal capillaries, and retinal CD shows a negative correlation with disease duration in PSS. This study was not registered to clinicaltrials.gov.

Go Ask Your Patients! PSS-QoL Reported Perception of Dryness Correlates With Lacrimal and Salivary Flow in Primary Sjögren's Syndrome.

Introduction/Objectives: The patient perspective is an essential outcome parameter in the quest for effective therapy in primary Sjögren's Syndrome (PSS). The EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is recommended by EULAR to quantify patient's symptom burden and has been used in several clinical trials. Surprisingly, the patient's perception of dryness quantified with ESSPRI does not correlate with objective measures of salivary or lacrimal flow. Thus, we evaluated a newly developed assessment tool-the Primary Sjögren's Syndrome Quality of Life Questionnaire (PSS-QoL)—for quantifying symptoms of dryness in comparison with the ESSPRI and objective measurements of salivary and lacrimal flow.Methods: Data of patients from the PSS registry of the Medical University of Graz fulfilling the 2016 ACR/EULAR classification criteria for PSS were analyzed. The patient perspective was analyzed by PSS-QoL, ESSPRI, Xerostomia Inventory (XI) and Ocular Surface Disease Index (OSDI). Sicca signs were measured with Schirmer's test, unstimulated salivary flow test (USF) and stimulated salivary flow test (SSF). ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index) and EGA (Evaluator Global Assessment, numeric rating scale from 0 to 10) were obtained. In addition, free light chains (FLC) κ and λ, rheumatoid factor (RF) IgM and IgA were determined.Results: Data from 123 PSS patients were analyzed; 91.9% (n = 113) were female, with a mean disease duration of 6.2 (±5.3) years and mean age of 60.1 (±12.4) years. PSS-QoL-dryness revealed significant negative correlations with Schirmer's test (r = −0.31, p < 0.05) and SSF-test (r = −0.390, p < 0.01). In contrast, we found no significant correlation between ESSPRI-dryness and any objective dryness test. Lower perceived dryness was associated with higher immunological activity determined by increased levels of IgG, FLC and RF-IgA. Whereas patients with only subjective signs of dryness had lower immunological activity.Discussion: Patients' perception of dryness assessed by PSS-QoL correlates with objective measurements of salivary gland function while ESSPRI-dryness did not. Based on the PSS-QoL and objective measures of dryness two distinct groups of PSS patients could be distinguished, which may have implications in daily practice and future clinical studies.

Disease phenotype and diagnostic delay in Saudi patients with primary Sjögren's syndrome: An exploratory cross-sectional study.

Objectives:To describe primary Sjögren’s syndrome (pSS) cohort in Saudi Arabiain view in of clinical/serological/histopathological phentotype, and, diagnostic delay.Methods:A cross-sectional study conducted between October 2018 and May 2019. Diagnostic delay was calculated from symptoms onset to clinical diagnosis. The European League Against Rheumatism (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI) and EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI) were calculated.Results:Forty-one patients were included in the study. There were predominantly females (78%) with a mean (±SD) age of 58.76±12.7 and disease duration of 4.6±2.28 years. The mean diagnostic delay was 2.2±2.4 (range 1-11) years. Minor salivary gland biopsy was performed on 38 (92.7%) patients with a mean focus score of 2.3± 1.2 points. Interstitial lung disease and arthritis were the most common extra-glandular manifestations (EGM) affecting 27 (65.9%) patients for both. The mean ESSDAI was 9.95±7.73 and ESSPRI was 5.17±2.4.Conclusion:Saudi primary Sjogren’s syndrome patients have a high prevalence of EGM predominantly arthritis and ILD. The diagnostic delay is variable in our cohort.

Leukocyte Immunoglobulin-Like Receptor A3 (LILRA3): A Novel Marker for Lymphoma Development among Patients with Young Onset Sjogren's Syndrome.

Background: Primary Sjogren’s syndrome (SS) is an autoimmune disease with a strong predilection for lymphoma development, with earlier disease onset being postulated as an independent risk factor for this complication. Variations of the Leukocyte immunoglobulin-like receptor A3 (LILRA3) gene have been previously shown to increase susceptibility for both SS and non-Hodgkin B-cell lymphoma (B-NHL) in the general population. We aimed to investigate whether variations of the LILRA3 gene could predispose for lymphoma development in the context of SS. Methods: Study population, all of Greek origin, included 101 SS cases with a current or previous diagnosis of lymphoma (SS-lymphoma, SS-L) and 301 primary SS patients not complicated by lymphoma (SS-non-lymphoma, SS-nL). All SS patients fulfilled the 2016 SS American College of Rheumatology/European league against Rheumatism (ACR/EULAR) classification criteria. A total of 381 healthy controls (HC) of similar age/sex/race distribution were also included. On the basis of the age of SS onset and the presence or absence of adverse predictors for lymphoma development, SS patients were further stratified into younger (≤40 years) and older (>40 years) age of disease onset, as well as into high/medium and low risk groups. Polymerase chain reaction (PCR) was implemented for the detection of the following LILRA3 gene variants: homozygous non-deleted or functional wild type (+/+) heterozygous (+/−) and homozygous deleted (−/−). LILRA3 serum protein levels were quantitated by enzyme-linked immunosorbent assay (ELISA) in 85 individuals (29 SS-L, 35 SS-nL patients and 21 HC). Results: While no statistically significant differences were detected in the overall frequency of LILRA3 gene variants between SS-L, SS-nL and HC groups, LILRA3 serum protein levels were increased in the SS-L group compared to HC (1.27 ± 1.34 vs. 0.38 ± 0.34 ng/mL, p-value: 0.004). After stratification according to the age of SS onset and history of lymphoma, as well as the presence or absence of adverse predictors for lymphoma development, the prevalence of the functional LILRA3 gene variant was found to be significantly increased in the young onset SS-L group compared to the HC of similar age and sex distribution (100% vs. 82.9%, p = 0.03), as well as in the high/medium risk SS compared to the low risk SS (91.3 vs. 78.3%, p = 0.0012). Of note, young onset SS-L and SS-nL groups displayed higher LILRA3 serum levels compared to their older counterparts (p-values: 0.007 and 0.0005, respectively). Conclusion: The functional LILRA3 gene variant increases susceptibility to SS-related lymphoma development in patients with a disease onset of <40 years old, implying that genetically determined deranged immune responses in younger SS individuals could underly their pronounced risk for lymphoma development.

Haematologic indices and disease activity index in primary Sjogren's syndrome

The present study was conducted to investigate the association between haematologic indices, neutrophil/lymphocyte ratio (NLR), mean platelet volume (MPV), platelet/lymphocyte ratio (PLR), disease activation, organ involvement, and inflammatory markers in the SS. The study was conducted with newly diagnosed and treatment-naive 41 primary SS patients who met ACR-2012 criteria and 96 healthy volunteers. Blood tests obtained before treatment were evaluated. Lymphocyte, neutrophil and platelet counts, mean corpuscular volume (MCV), platelet distribution width (PDW), plateletcrit (PCT), haematocrit (HCT), MPV, white blood cell count (WBC) values were harvested from CBC of the subjects and NLR, PLR were calculated over these values. The values were compared between groups and correlation with EULAR SS disease activity index (ESSDAI) was evaluated. The study included a total of 41 patients with a mean age of 40.73±12.0years and 96 healthy subjects with a mean age of 40.0±9.2years. In inter-group comparisons, lymphocyte, platelet counts, and MPV values were significantly lower in the SS group compared with the control group (P<.01), and NLR was significantly higher in the SS group (P=.026). The mean ESSDAI scores in SS patients were 5.65±0.86 SE. These scores were significantly higher in patients with neurological involvement. There was a positive correlation between ESSDAI and PLR. NLR, PLR, and MPV may be used as indicators or with activity index in SS. ESSDAI scores were found to be high in patients with neurological involvement, and it was also found to be correlated with PLR.

Pericarditis as an initial manifestation of Sjögren syndrome in a child

Abstract Introduction: Primary Sjögren syndrome (SS) is a chronic systemic autoimmune disease characterized by lymphocytic inflammation of exocrine glands and epithelia in multiple sites. SS is usually difficult to diagnose particularly in children because SS is rare for this age group, and various clinical signs and symptoms, without typical sicca symptoms, are shown as initial manifestations in pediatric SS patients. There have been no reports on cases of pediatric primary SS with symptomatic pericarditis being the initial manifestation. We report a case of primary SS in a pediatric patient who developed symptomatic pericarditis. Patient concerns: An 11-year-old girl presented with a 2-day history of fever, and chest and left shoulder pains. The pain was exacerbated when she was in a supine position. Diffuse ST-segment elevations on the electrocardiogram, presence of pericardial friction sounds, exacerbation of diastolic pericardial effusion on the echocardiogram, and continuous chest pain indicated acute symptomatic pericarditis. Diagnosis: The results of the blood antibody test, salivary gland scintigram, and salivary gland biopsy led to the diagnosis of SS. Also, this patient has no hypocomplementemia, and classification criteria of American College of Rheumatology of systemic lupus erythematosus and mixed connective tissue disease were not fulfilled. Intervention: Prednisolone therapy relieved her symptoms. Subclinical Hashimoto's thyroiditis, a well-known complication of primary SS, was observed; however, prescriptions were not needed. Outcomes: The clinical signs and symptoms of systemic lupus erythematosus and mixed connective tissue disease were not observed when prednisolone was tapered. During the 1-year treatment and follow-up period, the patient had no symptom recurrence. Conclusions: In pediatric primary SS patients, clinically silent heart changes are common, but obvious heart involvement is extremely rare. Unusual initial symptoms, such as symptomatic pericarditis, should not be missed in childhood-onset primary SS.

Increased expression of interleukin-21-inducible genes in minor salivary glands are associated with primary Sjögren's syndrome disease characteristics.

To determine the upregulation of IL-21-inducible genes in minor salivary glands (MSGs) in 28 primary SS (pSS) patients and 12 non-pSS subjects and correlate it with disease characteristics. RNA sequencing was utilized to compare IL-21-inducible genes expression in the MSGs between pSS and non-pSS subjects. The subgroups were characterized according to the IL-21 score calculated by seven IL-21-inducible genes. Furthermore, the disease characteristics and transcripts implicated in hypoxia and interferon signalling were assessed in two pSS subgroups. We observed that the expression of the IL-21-inducible genes (IL-21, IL-21R, JAK3, STAT1, HLA-B, CCR7 and CXCL10), the so-called IL-21 signature genes, was significantly increased in pSS patients. The upregulation of JAK3 expression may be induced by hypomethylation of the JAK3 promoter in pSS patients and putatively associated with POU2F2. The patients with increased IL-21 signature gene expression showed an increased EULAR Sjögren's Syndrome Disease Activity Index score and increased enrichment of B cells, memory B cells, CD4+ T cells and CD8+ T cells. Furthermore, the IL-21 scores in the anti-SSA+, SSB+, ANA+ and high IgG samples were higher than those in the respective antibody-negative samples and normal IgG. In addition, we found both hypoxia and IFN-relevant genes showed strong correlation with IL-21 signature gene expression, indicating their interaction in pSS. IL-21 signature gene was associated with typical disease characteristics in pSS, which provides insight into the contribution of the IL-21 signalling pathway to the pathogenesis of the disease and might provide a novel treatment strategy for this subtype of pSS.

Inhibition of JAK-STAT Signaling by Baricitinib Reduces Interferon-γ-Induced CXCL10 Production in Human Salivary Gland Ductal Cells.

Sjögren's syndrome (SS) is a chronic autoimmune disease targeting salivary and lacrimal glands. C-X-C motif chemokine ligand 10 (CXCL10) expression is upregulated in lip salivary glands (LSGs) of primary SS (pSS) patients, and CXCL10 involved in SS pathogenesis via immune-cell accumulation. Moreover, interferon (IFN)-γ enhances CXCL10 production via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. We investigated the effects of baricitinib, a selective JAK1/2 inhibitor, on both IFN-γ-induced CXCL10 production and immune-cell chemotaxis. We used immunohistochemical staining to determine the expression levels and localization of JAK1 and JAK2 in LSGs of SS patients (n = 12) and healthy controls (n = 3). We then evaluated the effect of baricitinib in an immortalized normal human salivary gland ductal (NS-SV-DC) cell line. Immunohistochemical analysis of LSGs from pSS patients revealed strong JAK1 and JAK2 expression in ductal and acinar cells, respectively. Baricitinib significantly inhibited IFN-γ-induced CXCL10 expression as well as the protein levels in an immortalized human salivary gland ductal-cell clone in a dose-dependent manner. Additionally, western blot analysis showed that baricitinib suppressed the IFN-γ-induced phosphorylation of STAT1 and STAT3, with a stronger effect observed in the case of STAT1. It also inhibited IFN-γ-mediated chemotaxis of Jurkat T cells. These results suggested that baricitinib suppressed IFN-γ-induced CXCL10 expression and attenuated immune-cell chemotaxis by inhibiting JAK/STAT signaling, suggesting its potential as a therapeutic strategy for pSS.

Activation of AIM2 inflammasome in salivary gland epithelial cells of patients with primary Sjögren’s syndrome

Abstract Sjögren’s syndrome (SS) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration in the exocrine glands. Although an association between inflammasome activation in peripheral blood cells and disease activity of SS has been reported, little is known about inflammasome activation in exocrine glands and its underlying mechanisms. We investigated the levels of AIM2, ASC, caspase-1, IL-1β, and IL-18 in salivary gland tissues and saliva from SS patients. We found that AIM2, ASC, Caspase-1, and IL-18 were increased in the saliva from primary SS patients compared with healthy and sicca controls. Numbers of AIM2-ASC speck also were elevated in the salivary gland epithelial cells of SS patients. The expression of caspase-1 correlated with type I interferon (IFN) signature gene expressions in the minor salivary glands (MSG) of SS patients, and was increased by type I IFN stimulation in salivary gland epithelial cells (SGECs). The AIM2 inflammasome was activated in SGECs after stimulation by the AIM2 ligand, poly(dA:dT). In addition, type I IFN accelerated AIM2 inflammasome activation as determined by the increased expression of caspase-1 in SGECs. In conclusion, the AIM2 inflammasome activation is increased in the SGECs of SS patients, and therefore should be considered an important pathogenic mediator of SS disease.

Vaginal dryness in primary Sjögren's syndrome: a histopathological case-control study.

ObjectiveThe aim was to study clinical, histopathological and immunological changes in the vagina and cervix of women with primary SS, which might explain vaginal dryness.MethodsWe included 10 pre-menopausal female primary SS patients with vaginal dryness and 10 pre-menopausal controls undergoing a laparoscopic procedure. The vaginal health index was recorded. Multiplex immunoassays and flow cytometry were performed on endocervical swab and cervicovaginal lavage samples to evaluate cellular and soluble immune markers. Mid-vaginal and endocervical biopsies were taken and stained for various leucocyte markers, caldesmon (smooth muscle cells), avian V-ets erythroblastosis virus E26 oncogene homologue (ERG; endothelial cells) and anti-podoplanin (lymphatic endothelium). The number of positive pixels per square micrometre was calculated.ResultsOne patient was excluded because of Clamydia trachomatis, and two controls were excluded because of endometriosis observed during their laparoscopy. Vaginal health was impaired in primary SS. CD45+ cells were increased in vaginal biopsies of women with primary SS compared with controls. Infiltrates were predominantly located in the peri-epithelial region, and mostly consisted of CD3+ lymphocytes. In the endocervix, CD45+ infiltrates were present in patients and in controls, but a higher number of B lymphocytes was seen in primary SS. Vascular smooth muscle cells were decreased in the vagina of primary SS patients. No differences were found in leucocyte subsets in the vaginal and endocervical lumen. CXCL10 was increased in endocervical swab samples of primary SS patients.ConclusionWomen with primary SS show impaired vaginal health and increased lymphocytic infiltration in the vagina compared with controls. Vaginal dryness in primary SS might be caused by vascular dysfunction, possibly induced by IFN-mediated pathways.

Bcl6 for identification of germinal centres in salivary gland biopsies in primary Sjögren's syndrome.

Histopathological assessment of salivary gland biopsies is an important element of the diagnostic work-up of Sjogren's syndrome (SS) (Fox, 2017; Kroese et al., 2018). Microscopic evaluation of salivary glands of primary SS (pSS) patients reveals characteristic periductal lymphocytic infiltrates (foci), which mainly consist of T- and B-lymphocytes, as well as a variety of non-lymphoid cells, including dendritic cells and macrophages. Over time, these infiltrates may become organised to ectopic lymphoid tissue with T/B cell compartmentalisation, presence of CD21+ follicular dendritic cell (FDC) networks and high endothelial venules (Fisher et al., 2017; Kroese et al., 2014; Kroese et al., 2018; Salomonsson et al., 2003).

Clinical profile and associated factors of pulmonary involvement in primary Sjögren's syndrome

ObjectivesThe aim of this study is to identify the clinical characteristics of primary Sjögren's syndrome (PSS) patients with pulmonary involvement and the associated factors for pulmonary involvement in PSS. MethodsWe retrospectively reviewed clinical features, laboratory examinations, imaging tests, pathological results and therapeutic strategy of 367 PSS patients. Comparisons were made between two subgroups: PSS with pulmonary involvement and those without. Correlation between the pathology of minor salivary gland biopsy (MSGB) and diverse features with pulmonary involvement were detected by Pearson correlation analysis and associated factors were selected by multivariate logistic regression analysis. ResultsThe lung involved PSS patients had significantly higher level of inflammatory associated indexes (p<0.05). There is no significant correlation between pathology of MSGB and lung involvements. Age, elevated neutrophils level and hypoproteinemia are significantly associated with lung disease with in PSS cohort (p<0.05). As for therapeutic strategy, moderate dose prednisone (15–40mg/d) and cyclophosphamide (CTX) are mainly different between two subgroups. ConclusionsPSS patients with pulmonary involvements show enhanced inflammation. Age, elevated neutrophils level and hypoproteinemia are independent associated with pulmonary involvements in PSS patients. For those PSS with pulmonary involvement moderate dose of prednisone and CTX were still the mainstream.

Case report on a 32-year-old female with elevated serum creatinine levels and primary Sjögren's syndrome-chronic interstitial nephritis.

Primary Sjögren's syndrome (PSS) is a chronic autoimmune disease characterized by lymphoplasmacytic infiltration of the exocrine glands, which results in multiple organs damage. Renal injury affects 0.3–27.0% of PSS patients, and tubulointerstitial nephritis is the most frequent form of nephropathy in PSS. The present study reports on the case of a 32-year-old female with a 1-year history of elevated serum creatinine levels, and a 6-month history of mild pain in the waist and leg. Blood biochemistry tests indicated a creatinine level of 221.3 µmol/l and estimated glomerular filtration rate of 24.6 ml/min/1.73 m2 [Chronic Kidney Disease Epidemiology (CKD-EPI) formula]. Accordingly, the patient was diagnosed with stage IV chronic kidney disease. To clarify the underlying cause of the disease, a kidney biopsy was performed, which revealed tubular epithelial cells with multiple focal and lamellar atrophy (~60%), as well as extensive renal interstitial fibrosis with scattered inflammatory cell infiltration. Based on these results, the patient was finally diagnosed with severe chronic interstitial nephritis, chronic kidney disease stage IV, PSS and anemia due to chronic kidney disease. The patient was treated with half-dose glucocorticoid (prednisone, 25 mg oral qd maintained up to 12 months). The patient's serum creatinine levels had decreased to 172.4 µmol/l after 1 month and to 178.7 µmol/l after 12 months. The present case concluded that young patients with chronic renal failure should first be assessed for rheumatic immune system diseases. PSS may involve several organs and the clinical manifestations may be varied. Although chronic renal failure is frequently the first manifestation of renal disorder due to PSS, it may be overlooked by clinicians. The present results suggest that further attention should be paid to determine the association between symptoms in the clinical setting.

Oral Lichen Planus and Lichenoid Lesions in Sjogren's Syndrome Patients: A Prospective Study.

Objective The aim of this study was to investigate the prevalence and characteristics of oral lichen planus (OLP) and oral lichenoid lesions (OLL) in Sjogren's syndrome (SS) patients. Patients and Methods A prospective clinical study was conducted at the Department of Oral Medicine and Oral Surgery in Sahloul Hospital, Sousse, from January 2012 to June 2018. The patients involved in this study were diagnosed with Sjogren's syndrome according to the AECG (American-European consensus group) diagnostic criteria. Among these patients, we searched for those affected by OLP or OLL as determined by the WHO (World Health Organisation) classification of 2003. Clinical variables such as age, sex, medical conditions and medications, type of SS (primary or secondary), clinical form of OLP, and treatment were analyzed. The assessment of the results was performed using SPSS software. Results We evaluated 30 patients (27 females and 3 males) diagnosed with SS (24 had primary SS) with a mean age of 55 years and 11 months (±11,714). Overall, 9 patients had oral lesions (30%). Two patients had OLP associated with secondary SS (25%). Primary Sjogren's syndrome patients had 6 OLP lesions and one erythematous lichenoid lesion. OLP was erosive in eight patients, among them two had vulvo-vaginal-gingival syndrome. OLP lesions showed improvement in symptoms after topical or general corticosteroids treatment, while OLL showed improvement only under antibiotic treatment. Conclusion The results of our analysis suggest that patients with SS have 30% prevalence of OLP and OLL. This possible association shows the importance of screening for oral dryness in patients with OLP or OLL. Treatment includes topical or general corticosteroids for erosive forms associated or not with topical antifungal treatment to treat or prevent oral candidiasis.

Ablation of the Chaperone Protein ERdj5 Results in a Sjögren's Syndrome-Like Phenotype in Mice, Consistent With an Upregulated Unfolded Protein Response in Human Patients.

Objective: Sjögren's syndrome (SS) is a chronic autoimmune disorder that affects mainly the exocrine glands. Endoplasmic reticulum (ER) stress proteins have been suggested to participate in autoimmune and inflammatory responses, either acting as autoantigens, or by modulating factors of inflammation. The chaperone protein ERdj5 is an ER-resident disulfide reductase, required for the translocation of misfolded proteins during ER-associated protein degradation. In this study we investigated the role of ERdj5 in the salivary glands (SGs), in association with inflammation and autoimmunity.Methods: In situ expression of ERdj5 and XBP1 activation were studied immunohistochemically in minor SG tissues from primary SS patients and non-SS sicca-complaining controls. We used the mouse model of ERdj5 ablation and characterized its features: Histopathological, serological (antinuclear antibodies and cytokine levels), and functional (saliva flow rate).Results: ERdj5 was highly expressed in the minor SGs of SS patients, with stain intensity correlated to inflammatory lesion severity and anti-SSA/Ro positivity. Moreover, SS patients demonstrated higher XBP1 activation within the SGs. Remarkably, ablation of ERdj5 in mice conveyed many of the cardinal features of SS, like spontaneous inflammation in SGs with infiltrating T and B lymphocytes, distinct cytokine signature, excessive cell death, reduced saliva flow, and production of anti-SSA/Ro and anti-SSB/La autoantibodies. Notably, these features were more pronounced in female mice.Conclusions: Our findings suggest a critical connection between the function of the ER chaperone protein ERdj5 and autoimmune inflammatory responses in the SGs and provide evidence for a new, potent animal model of SS.

Clinical profile and associated factors of pulmonary involvement in primary Sjögren's syndrome

ObjectivesThe aim of this study is to identify the clinical characteristics of primary Sjögren's syndrome (PSS) patients with pulmonary involvement and the associated factors for pulmonary involvement in PSS. MethodsWe retrospectively reviewed clinical features, laboratory examinations, imaging tests, pathological results and therapeutic strategy of 367 PSS patients. Comparisons were made between two subgroups: PSS with pulmonary involvement and those without. Correlation between the pathology of minor salivary gland biopsy (MSGB) and diverse features with pulmonary involvement were detected by Pearson correlation analysis and associated factors were selected by multivariate logistic regression analysis. ResultsThe lung involved PSS patients had significantly higher level of inflammatory associated indexes (p<0.05). There is no significant correlation between pathology of MSGB and lung involvements. Age, elevated neutrophils level and hypoproteinemia are significantly associated with lung disease with in PSS cohort (p<0.05). As for therapeutic strategy, moderate dose prednisone (15–40mg/d) and cyclophosphamide (CTX) are mainly different between two subgroups. ConclusionsPSS patients with pulmonary involvements show enhanced inflammation. Age, elevated neutrophils level and hypoproteinemia are independent associated with pulmonary involvements in PSS patients. For those PSS with pulmonary involvement moderate dose of prednisone and CTX were still the mainstream.

Clinical features of Sj\xf6gren\u2019s syndrome patients with autoantibodies against interferons

BackgroundSjögren’s syndrome (SS) is an autoimmune disease characterized by immune attack on the salivary and lacrimal glands. Given the known cytokine activation and type I interferon gene expression signature found in SS, we hypothesized that anticytokine autoantibodies might be detectable by Luciferase immunoprecipitation systems in some SS patients and correlate with clinical symptoms.ResultsLuciferase immunoprecipitation systems was used to screen for serum anti-cytokine autoantibodies in 57 primary SS patients and 25 healthy volunteers. Autoantibodies were detected against GMCSF, interferon-γ, -α and, -ω in one, two, two and six patients with SS, respectively. None of the healthy volunteers showed anticytokine autoantibodies and none of the SS or control subjects showed autoantibodies against interferon-λ. One 51-year old female SS subject with the highest anti-interferon-α and -ω autoantibody levels had stable autoantibody levels over the course of a year. In vitro functional testing of serum autoantibodies from this subject demonstrated partially neutralizing activity for interferon-α signaling. Clinical information on this individual revealed a low focus score and high levels of unstimulated salivary flow, suggesting the possibility that interferon-α autoantibody neutralizing activity may have contributed to the milder sicca symptoms.ConclusionOverall, these findings demonstrate that a subset of SS patients (16%) harbor autoantibodies against GMCSF, interferon-γ, interferon-ω, and interferon-α. These data support the observation that high levels of interferon-α autoantibodies may attenuate disease symptoms in SS.

Quantitative Analysis of Parotid Gland Secretion Function in Sjögren's Syndrome Patients with Dynamic Magnetic Resonance Sialography.

ObjectiveTo evaluate the secretory function of parotid glands by dynamic magnetic resonance (MR) sialography and determine the clinical performance of this technique in diagnosing and evaluating Sjögren's syndrome (SS) patients.Materials and MethodsThis study enrolled 29 healthy volunteers (25 women and 4 men; mean age, 34.8 ± 6.3 years; age range, 26–47 years) and 25 primary SS (pSS) patients (23 women and 2 men; mean age, 37.7 ± 7.9 years; age range, 25–50 years) with decreased secretory function. The volume of the parotid gland ducts was precisely measured for both groups at single pre- and 6 post-gustatory-stimulated phases. Time-dependent volume change ratio curves were generated, four parameters were derived from the curves: the slope of the increase in the first post-stimulation phase (slope1st), the peak value, the time-to-peak, the total saliva secretion post-stimulation. All values were used to quantitatively evaluate the secretory function of the parotid gland. The repeated measurement analysis, Mann-Whitney U test and receiver operating characteristic curve were applied.ResultsTime-dependent volume change ratio curves demonstrated that there is a statistically significant difference between the two groups (F = 8.750; p = 0.005). A quickly increasing curve was shown in the volunteer group, whereas a slowly increasing curve was shown in the pSS patient group. The slope1st, peak value and total saliva secretion post-stimulation of the patient group were significantly lower than those of the volunteer group (p = 0.005, p = 0.003, and p = 0.002, respectively). The time-to-peak between the two groups was not significantly different (p = 0.383). The slope1st can be used as a discriminator to diagnose SS patients (p = 0.015; odds ratio = 4.234; area under the curve = 0.726).ConclusionDynamic MR sialography is proven to be an effective method in evaluating salivary gland function and has a great potential in diagnosing and evaluating pSS patients.