Syndrome Disease Activity Index Research Articles

Comprehensive analysis of the clinical manifestations and hematological parameters associated with secondary immune thrombocytopenia in patients with primary Sjögren syndrome: An observational study.

Primary Sjögren Syndrome (pSS) is a chronic autoimmune disease that primarily affects exocrine glands and can lead to various extraglandular manifestations, including secondary immune thrombocytopenia (ITP). Understanding the clinical and hematological differences in pSS patients with and without secondary ITP is crucial for improved patient management and treatment strategies. This retrospective study, conducted from January 2020 to December 2023, involved a cohort of pSS patients, dividing them into 2 groups: those with secondary ITP and those without. Patients were evaluated using the European League Against Rheumatism Sjögren Syndrome Disease Activity Index (ESSDAI), EULAR Sjögren Syndrome Patient-Reported Index (ESSPRI), Health Assessment Questionnaire, and other hematological parameters. Inclusion criteria were based on the American-European Consensus Group or ACR/EULAR classification criteria for pSS. Exclusion criteria included other autoimmune or hematological disorders, prior splenectomy, recent blood transfusions, and lack of informed consent. Statistical analysis was performed using SPSS software, with various tests applied to analyze the data, including logistic regression to identify risk factors for secondary ITP. Significant differences were noted in fatigue, lymphadenopathy, arthritis, mean age, and ESSDAI scores between the secondary ITP and non-secondary ITP groups. Patients with secondary ITP exhibited higher platelet counts, more prevalent lymphopenia, higher immunoglobulin G (IgG) levels, lower complement 3 levels, and reduced white blood cell and hemoglobin levels. Logistic regression analysis identified lymphadenopathy as a risk factor and arthritis as a protective factor for the development of secondary ITP. The study reveals distinct clinical and hematological characteristics in pSS patients with secondary ITP, suggesting a higher disease activity in this subset. These findings underscore the need for further exploration of these associations to develop more precise treatment approaches for pSS, focusing on preventing secondary ITP and improving patient outcomes.

P153 Exploring the relationships between objective and subjective clinical measures in Sjogren's Syndrome

Abstract Background/Aims Patient Reported Outcome Measures (PROMs) are standardised, validated questionnaires designed to measure the patient’s perception of their disease. Discordance between the patient’s perspective and objective clinical measures (clinical scores, laboratory data) has led to increased interest in PROMs in Sjogren’s syndrome (SS). Initial concern about the subjectivity of PROMs has given way to methodological rigour and clear guidance for the development of PROMs. Several studies have now used PROMs for symptom-based stratification, and recently researchers have developed composite disease assessment tools incorporating PROMs and objective clinical measures to create more clinically meaningful endpoints for SS trials. With the advent of PROM-based stratification tools and composite endpoints, it is vital to better understand the relationship between clinical measures in SS. In this project we performed network analysis with data from a large cohort of well-characterised SS patient to improve our understanding of the relationship between objectively measured parameters and PROMs. Methods The UK Primary Sjogren’s Syndrome Registry (UKPSSR) is a nationwide observational cohort of primary SS patients who fulfil the 2002 American European Consensus Group classification criteria. The UKPSSR holds detailed clinical and laboratory data that is collected prospectively, including patient-reported outcomes collected using standardized questionnaires. To assess concordance between clinical measures we used the ARACNE algorithm, which calculates mutual information between the variables of a multidimensional dataset to construct a network of shared information. Statistical analysis was performed in R-v4.1.3 and JMP Pro-v15 and network visualisation in Cytoscape-v3.8.2. Results The ARACNE network highlights key areas of concordance and discordance between PROMs, clinician-based and laboratory-based measurements. Providing assurance to this approach, multi-domain PROMs and ESSDAI (EULAR Sjögren's syndrome disease activity index) subdomains are strongly associated with their component scores and different PROMs measuring the same symptoms were also correlated. In contrast, there is a clear separation between PROMs, clinician-based and laboratory-based measurements each forming their own sub-networks. Furthermore, most laboratory measurements do not have strong relationship with clinician-based disease activity score or PROMs. EQ-5D utility and HADS (Hospital Anxiety and Depression Scale) values provide the primary link between ESSPRI (EULAR Sjogren's Syndrome Patient Reported Index) and ESSDAI subdomain scores and both ESSDAI and ESSPRI are important contributors to quality-of-life. Conclusion The dissociation between PROMs and objective clinical measures is important for clinical management and trial design. Whilst it complicates clinical management of SS including any treat-to-target strategy; it highlights the importance of PROMs in supporting clinician assessment and laboratory measurements to better capture all aspects of SS and give a more individualised, meaningful assessment. Finally, it supports the dual-target strategy of systemically pursuing two targets in the design of clinical trials: one focused on the disease activity and another focused on the symptoms and impact. Disclosure J.S. Berry: None. J. Tarn: None. D. Lendrem: None. J. Casement: None. W. Ng: Consultancies; Expert advice in the area of Sjogren’s syndrome to GlaxoSmithKline, MedImmune, UCB, Abbvie, Roche, Eli Lilly, Takeda, Resolves Therapeutics, Sanofi, Novartis and BMS.

Primary Sjögren’s syndrome independently promotes premature subclinical atherosclerosis

ObjectivesCardiovascular comorbidities are common in patients with autoimmune diseases. This study investigates the extent of subclinical atherosclerosis in patients with primary Sjögren’s syndrome (pSS). Correlations with clinical factors such as...

The proportion of CD161 on CD56+ NK cells in peripheral circulation associates with clinical features and disease activity of primary Sjögren's syndrome.

The purpose of this study was to examine the proportion of CD161 on CD56+ natural killer (NK) cells in peripheral blood of primary Sjögren's syndrome (pSS) and investigate its clinical relevance of pSS. The proportion of CD56+ NK cells and CD161 on CD56+ NK cells was detected by flow cytometry in 31 pSS patients and 29 healthy controls (HCs). The correlations between the proportion of CD161+CD56+ NK cells and clinical features and disease activity of pSS were further analyzed. Meanwhile, we drew the receiver operating characteristic curve to evaluate the diagnostic value of CD161+CD56+ NK cells in pSS. In addition, we evaluated the differences in the effects of CD161+ cells and CD161- cells in peripheral blood on the function of CD56+ NK cells in 5 pSS patients. The proportion of CD56+ NK cells and CD161+CD56+ NK cells decreased markedly in pSS patients compared to HCs. The correlation analysis showed that the proportion of CD161+CD56+ NK cells negatively correlated with white blood cells, Immunoglobulin A (IgA), IgM, IgG, European League Against Rheumatism Sjogren's Syndrome Patient Reported Index andEuropean League Against Rheumatism Sjogren's Syndrome Disease Activity Index, and positively correlated with complement C4. The proportion of CD161+CD56+ NK cells in pSS patients with decayed tooth, fatigue, arthralgia, skin involvement, primary biliary cirrhosis, interstitial lung disease, anti-SSA/Ro60 positive, anti-SSB positive and high IgG was lower than that in negative patients. Furthermore, compared with inactive patients, the proportion of CD161+CD56+ NK cells decreased obviously in active patients. The area under the curve was 0.7375 (p = .0016), the results indicated that CD161+CD56+ NK cells had certain diagnostic values for pSS. In addition, the proportion of CD86, HLA-DR, Ki67, FasL, TNF-α, and IFN-γ on CD161+CD56+ NK cells was lower than that on CD161-CD56+ NK cells in the peripheral blood of pSS patients. This study suggested that the proportion of CD56+ NK cells and CD161+CD56+ NK cells decreased significantly in pSS patients, and the proportion of CD161+CD56+ NK cells negatively associated with the clinical features and disease activity of pSS patients. CD161 expression inhibited the function of CD56+ NK cells in peripheral blood of pSS patients. The CD161+CD56+ NK cells may present as a potential target for therapy and a biomarker of disease activity in pSS.

Identification of distinct subgroups of Sjögren's disease by cluster analysis based on clinical and biological manifestations: data from the cross-sectional Paris-Saclay and the prospective ASSESS cohorts

Sjögren's disease is a heterogenous autoimmune disease with a wide range of symptoms-including dryness, fatigue, and pain-in addition to systemic manifestations and an increased risk of lymphoma. We aimed to identify distinct subgroups of the disease, using cluster analysis based on subjective symptoms and clinical and biological manifestations, and to compare the prognoses of patients in these subgroups. This study included patients with Sjögren's disease from two independent cohorts in France: the cross-sectional Paris-Saclay cohort and the prospective Assessment of Systemic Signs and Evolution of Sjögren's Syndrome (ASSESS) cohort. We first used an unsupervised multiple correspondence analysis to identify clusters within the Paris-Saclay cohort using 26 variables comprising patient-reported symptoms and clinical and biological manifestations. Next, we validated these clusters using patients from the ASSESS cohort. Changes in disease activity (measured by the European Alliance of Associations for Rheumatology [EULAR] Sjögren's Syndrome Disease Activity Index [ESSDAI]), patient-acceptable symptom state (measured by the EULAR Sjögren's Syndrome Patient Reported Index [ESSPRI]), and lymphoma incidence during follow-up were compared between clusters. Finally, we compared our clusters with the symptom-based subgroups previously described by Tarn and colleagues. 534 patients from the Paris-Saclay cohort (502 [94%] women, 32 [6%] men, median age 54 years [IQR 43-64]), recruited between 1999 and 2022, and 395 patients from the ASSESS cohort (370 [94%] women, 25 [6%] men, median age 53 years [43-63]), recruited between 2006 and 2009, were included in this study. In both cohorts, hierarchical cluster analysis revealed three distinct subgroups of patients: those with B-cell active disease and low symptom burden (BALS), those with high systemic disease activity (HSA), and those with low systemic disease activity and high symptom burden (LSAHS). During follow-up in the ASSESS cohort, disease activity and symptom states worsened for patients in the BALS cluster (67 [36%] of 186 patients with ESSPRI score <5 at month 60 vs 92 [49%] of 186 at inclusion; p<0·0001). Lymphomas occurred in patients in the BALS cluster (five [3%] of 186 patients; diagnosed a median of 70 months [IQR 42-104] after inclusion) and the HSA cluster (six [4%] of 158 patients; diagnosed 23 months [13-83] after inclusion). All patients from the Paris-Saclay cohort with a history of lymphoma were in the BALS and HSA clusters. This unsupervised clustering classification based on symptoms and clinical and biological manifestations did not correlate with a previous classification based on symptoms only. On the basis of symptoms and clinical and biological manifestations, we identified three distinct subgroups of patients with Sjögren's disease with different prognoses. Our results suggest that these subgroups represent different heterogeneous pathophysiological disease mechanisms, stages of disease, or both. These findings could be of interest when stratifying patients in future therapeutic trials. Fondation pour la Recherche Médicale, French Ministry of Health, French Society of Rheumatology, Innovative Medicines Initiative 2 Joint Undertaking, Medical Research Council UK, and Foundation for Research in Rheumatology.

New‐onset primary Sjögren's syndrome following exposure to severe acute respiratory syndrome coronavirus 2: A retrospective cohort study

AbstractBackgroundUnderstanding the clinical implications of autoimmune manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is essential to reduce its consequences. This study was aimed at determining the activities of new‐onset primary Sjögren syndrome (pSS) since the emergence of SARS‐CoV‐2.MethodsThis retrospective cohort study included data from 471 participants with dry mouths and eyes who had been attending Nanjing Drum Tower Hospital since December 2019. By April 2023, patients diagnosed with pSS were sequentially assigned to vaccinated group (n = 24) or vaccinated and infected group based on exposure (n = 20). Patients diagnosed with pSS within 3 months of vaccination against SARS‐CoV‐2 were assigned to a vaccinated group, and those who had been vaccinated and then developed pSS within 3 months of follow up after direct exposure to SARS‐CoV‐2 were assigned to a vaccinated and infected group. The controls comprised age‐ and sex‐matched patients who had not been exposed to SARS‐CoV‐2 before December 2019 (n = 21). We then compared data among the three groups.ResultsThe vaccinated and infected patients had more fever, malaise, splenomegaly, and weight loss before diagnosis and a higher European Alliance of Associations for Rheumatology Sjögren's syndrome disease activity index at the time of onset than the other two groups. Vaccinated patients had a higher frequency of anti‐nuclear antibody (ANA) titers &gt; 1:320 (n = 12; 50%) and anti‐phospholipid antibodies (aPL) (n = 7; 29%) than the controls. The frequency of anti‐Ro/SSA antibodies (13, 65%), ANA titers &gt; 1:320 (n = 16; 80%), and aPLs (n = 7; 29%) (n = 5; 25%) were all significantly higher in vaccinated patients with infection than those in the controls. Higher doses of glucocorticoids, cyclosporin A, and tacrolimus were administered to the vaccinated and infected than the vaccinated and control groups (p &lt; 0.05, for all).ConclusionsPatients with new‐onset pSS and a history of vaccination and SARS‐CoV‐2 infection might have more active disease. Further strengthening the assessment of people with a clear history of SARS‐CoV infection and the monitoring of potential populations for autoimmune screening should not be overlooked.

Prognostic significance of lymphocytic foci composition in minor salivary gland biopsies for severe disease flare and severity in Sjögren's syndrome: a 3-year follow-up cohort study.

This was an ambispective cohort study evaluating the prognostic significance of lymphocytic foci and its lymphoid composition in minor salivary gland biopsy (MSGB) for short-term disease flare and severity in Sjögren's syndrome (SS). The inclusion criteria comprised individuals meeting the ACR/EULAR 2016 criteria who underwent MSGB with an infiltration of more than 50 lymphocytes and received clinical diagnosis between September 2017 and December 2018. Patients with inadequate biopsy samples were excluded. The number of lymphocytic foci and their lymphoid composition in MSGB were assessed using immunofluorescence staining. Major organ damage and improvements in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) were measured. Statistical analyses, including Cox and linear regressions, were conducted. A total of 78 patients with at least one lymphocytic focus were included in the study. The presence of higher T-cell counts in lymphocytic foci in MSGB was associated with severe disease flare, and a logarithmic transformation of T-cell count indicated increased risk (HR 1.96, 95% CI 0.91-4.21). Improvements in the ESSDAI were associated with higher total lymphocyte count and T- and B-cell numbers in the lymphoid composition of the lymphocytic foci. Seropositive patients exhibited higher T CD4+ cell numbers. Correlation analysis showed negative associations between age and lymphocytic foci and the T-cell count. Positive correlations were observed between antinuclear antibody (ANA) titers and total lymphocyte numbers. Patients with a higher number of T cells in the lymphocytic infiltrates of lymphocytic foci may have a two-fold risk of severe disease flare. The number of B cells and T CD4+ cells in the lymphocytic infiltrates of lymphocytic foci showed a weak but positive relation with the ESSDAI improvement during follow-up. Age and seropositivity appeared to influence the lymphoid composition of the lymphocytic foci.

Sjögren's disease activity associates with cardiovascular disease and monoclonal gammopathy: a university cohort study of disease activity and comorbidities.

We used the University of Wisconsin cohort to determine the extent to which the EULAR Sjögren's syndrome disease activity index (ESSDAI) was associated with comorbidities that contribute to mortality. Our University of Wisconsin, Madison cohort had 111 patients with Sjögren's Disease (SjD) by 2016 ACR/EULAR criteria and 194 control patients with sicca. Our study was performed from March 1st, 2020 through April 1st, 2023. We collected data using a standardized collection tool, including components of the Charlson Comorbidity Index (CCI). Stratifying our SjD patients by ESSDAI < 5 and ESSDAI ≥ 5, we assessed differences in comorbidities associated with mortality. At time of SjD diagnosis, the ESSDAI ≥ 5 group had increased odds of peripheral vascular disease compared to controls (OR 10.17; 95% CI 1.18-87.87). Patients with a current ESSDAI ≥ 5 were more likely to have a myocardial infarction compared to controls (OR 9.87; 95% CI 1.17-83.49). SjD patients had increased prevalence of monoclonal gammopathy compared to controls (9.3% vs 0.5%, p < 0.001). SjD patients with high ESSDAI at diagnosis had greater prevalence of monoclonal gammopathy compared to the SjD patients with a low ESSDAI (16% vs 5%, p = .04). As reported elsewhere, the ESSDAI ≥ 5 group had increased odds of chronic pulmonary disease (OR 4.37; 95% CI 1.59-11.97). We found high ESSDAI scores were associated with worse cardiovascular outcomes, specifically peripheral vascular disease and myocardial infarction. Furthermore, monoclonal gammopathy was more frequent in SjD patients compared to sicca controls, supporting screening for monoclonal gammopathy in the appropriate clinical scenario. Key Points • High ESSDAI scores are associated with worse cardiovascular outcomes, specifically peripheral vascular disease and myocardial infarction. • Monoclonal gammopathy is more frequent in SjD patients than sicca controls, supporting screening for monoclonal gammopathy in the appropriate clinical scenario.

Assessment of hydroxychloroquine blood levels in Sjögren's disease patients: drug adherence and clinical associations.

Hydroxychloroquine (HCQ) has been used to treat Sjögren's disease (SjD) patients. However, there are no studies evaluating drug adherence through HCQ blood levels, pharmacy refill (PR) and medication adherence questionnaires. The relationship of HCQ blood levels with glandular/extraglandular disease parameters was also poorly assessed. This cross-sectional observational study included 74 adult SjD patients, who were receiving a stable HCQ dose (4-5.5mg/kg/day, actual weight) for at least 3 months before study inclusion. HCQ blood levels were quantified by high-performance liquid chromatography coupled to mass spectrometry. Adherence was assessed by PR and Medida de Adesão aos Tratamentos (MAT) questionnaire. The following parameters were evaluated: Xerostomia Inventory, Ocular Surface Disease Index, EULAR (European League Against Rheumatism) Sjögren's Syndrome Disease Activity Index, EULAR Sjögren's Syndrome Patient Reported Index, Schirmer's I test and non-stimulated/stimulated salivary flow rates. HCQ blood levels were 775.3(25.0-2,568.6)ng/mL. Eleven patients (14.9%) had HCQ blood levels < 200ng/mL (non-adherent group); 11(14.9%), 200-499ng/mL (sub-therapeutic levels group); and 52(70.2%), ≥ 500ng/mL (adherent group). PR classified incorrectly all non-adherent/sub-therapeutic patients and 2/52(3.9%) adherent patients. Using MAT, the overall misclassification was 24/52(46.2%) in the adherent group, and were correctly identified 9/11(81.8%) patients in non-adherent and 7/11(63.6%) in sub-therapeutic groups. MAT sensitivity and specificity to identify non-adherent/sub-therapeutic patients were 72.7% and 53.9%, respectively. The three groups were comparable regarding glandular/extraglandular disease parameters (p > 0.05). The assessment of HCQ blood levels is a promising tool for evaluating drug adherence in SjD. This is particularly crucial as one-third of patients exhibited non-adherence/sub-therapeutic levels, and neither PR nor MAT reliably identified these patients.

CXCL9 may serve as a potential biomarker for primary Sjögren’s syndrome with extra-glandular manifestations

BackgroundPrimary Sjögren's syndrome (pSS) is an autoimmune condition that causes harm to exocrine glands and also has extra-glandular manifestations (EGM). pSS patients with EGM have a worse prognosis than those with only sicca symptoms. Previous studies have shown that the minor salivary glands (MSG) of pSS patients exhibit a unique profile of cytokines and chemokines compared to healthy controls. However, there is a lack of research comparing pSS with EGM (pSS-EGM) and pSS without EGM (pSS-non-EGM). This study aims to explore potential biomarkers associated with pSS, particularly pSS with EGM.MethodsBy utilizing RNA sequencing, we conducted an analysis on the gene expression profiles of MSG in 63 patients diagnosed with pSS, as well as 12 non-pSS individuals. Furthermore, we also investigated the MSG of pSS patients, both with and without EGM. Through bioinformatics analysis, we identified genes with differential expression (DEGs) and determined the core hub genes using PPI network. We then analyzed the top 20 DEGs and their correlation with the patients' clinical characteristics, and validated our findings using peripheral blood plasma.ResultsA total of 725 differentially expressed genes (DEGs) were identified in the comparison between pSS and non-pSS groups, and 727 DEGs were observed between pSS-EGM and pSS-non-EGM. It is noteworthy that the expression levels of CXCL9 were higher in both pSS patients and pSS-EGM when compared to the control group. Taking into consideration the significance of the top 20 DEGs in relation to clinical parameters and the central hub genes, we ultimately chose CXCL9. In comparison to the non-pSS group, pSS patients exhibited notably greater expression of the CXCL9 gene in the MSG, as well as higher levels of CXCL9 protein in their plasma (p < 0.001). Furthermore, the expression of the CXCL9 gene and levels of CXCL9 protein were notably higher in pSS patients accompanied by EGM and those with SSA antibodies. Additionally, a correlation was found between the expression of the CXCL9 gene and the EULAR Sjogren’s Syndrome Disease Activity Index (ESSDAI), as well as with immunoglobulin G (IgG) levels and erythrocyte sedimentation rate (ESR). Meanwhile, the protein levels of CXCL9 were found to be correlated with IgG levels and ESSDAI.ConclusionCXCL9 proves to be a valuable biomarker in pSS, specifically due to its strong ability to differentiate between pSS patients with EGM and those without EGM. There is a significant correlation between CXCL9 and various clinical parameters both at the gene and protein level. Therefore, CXCL9 could be a potential target for future treatment of pSS.

Involvement of CCL2 in Salivary Gland Response to Hyperosmolar Stress Related to Sjögren's Syndrome.

In primary Sjögren's syndrome (pSS) patients, salivary gland (SG) epithelial cells (SGECs) could be exposed to chronic hyperosmotic stress (HOS), consecutive to their destruction and deregulation, that exacerbates an inflammatory response. The aims of this study were to assess the mechanism accounting for C-C motif chemokine ligand 2 (CCL2) expression in an immortalized human salivary gland epithelial acinar cell line (NS-SV-AC) subjected to HOS, as well as the involvement of CCL2 in pSS. CCL2 mRNA and protein levels were determined via RT-qPCR and ELISA. Reporter plasmids and a promoter pull-down assay were used to identify transcription factors associated with CCL2 mRNA increase. Our data showed that HOS-induced CCL2 mRNA increase was independent of the nuclear factor of activated T-cells 5 (NFAT5) and nuclear factor-kappa B (NFkB) but involved Kruppel-like factor 5 (KLF5). CCL2 protein levels, quantified by enzyme-linked immunosorbent assay (ELISA) in sera samples from pSS patients, correlated with the European Alliance of Associations for Rheumatology's Sjogren's syndrome disease activity index (ESSDAI) score for systemic activity. In addition, CCL2 protein levels were higher in patients with biological activity, cutaneous manifestations, and ESSDAI score superior or equal to five. Our data suggest that chronic HOS could exacerbate pSS disease by contributing to the inflammatory process induced by the expression and secretion of CCL2.

Characteristics of primary Sjogren's syndrome with articular manifestations at initial treatment.

Articular manifestations have been reported in 19.3%-53.5% of patients with primary Sjogren's syndrome. Our aim was to profile the clinical characteristics of Chinese patients with primary Sjogren's syndrome who presented with articular manifestations at the time of initial treatment. We conducted a retrospective study of 129 primary Sjogren's syndrome patients admitted to the second Affiliated Hospital of Dalian Medical University between April 2016 and December 2021 for initial treatment. Clinical and serological features, extra-articular involvement, and initial treatment were compared between primary Sjogren's syndrome patients with and without articular manifestations. Fifty-seven (44.2%) primary Sjogren's syndrome patients had articular manifestations (mean age at diagnosis: 53.4 years), of which 42 (73.7%) presented with symmetrical distribution, 21 (36.8%) patients had rheumatoid factor positivity, and 11 (20.0%) patients had anti-cyclic citrullinated peptide antibodies positivity (mean 6.8 RU/mL); imaging examinations showed no signs of structural damage in these patients. The presence of articular manifestations showed positive correlation with anti-cyclic citrullinated peptide antibody level (odds ratio (OR) 1.01, 95% confidence interval (CI): 1.00-1.02; p = 0.049), C-reactive protein level (OR 1.15, 95% CI: 1.10-1.20; p = 0.000), and European League Against Rheumatism Sjogren syndrome disease activity index scores (OR 1.18, 95% CI: 1.11-1.25; p = 0.000). Ninety (69.8%) primary Sjogren's syndrome patients received hydroxychloroquine therapy. Hydroxychloroquine treatment was significantly less frequently used in articular manifestation patients (35 (70.0%) vs 55 (85.9%); p = 0.038). Symmetrical polyarthritis was the most common clinical manifestation of primary Sjogren's syndrome patients with articular manifestations in this cohort. Articular manifestations were associated with higher prevalence of C-reactive protein level, and European League Against Rheumatism Sjogren syndrome disease activity index score.

Tofacitinib in the treatment of primary Sjögren’s syndrome-associated interstitial lung disease: study protocol for a prospective, randomized, controlled and open-label trial

IntroductionTofacitinib, a selective inhibitor of JAK1 and/or JAK3, is considered to alleviate the pulmonary condition of primary Sjögren’s syndrome (pSS)-associated interstitial lung disease (ILD) through its anti-inflammatory and antifibrotic effects.Methods and analysisThis is a single-center, prospective, randomized, open-label trial. The trial will compare a 52-week course of oral tofacitinib with traditional therapy cyclophosphamide (CYC) combined with azathioprine (AZA) in the treatment of pSS-ILD. A total of 120 patients will be randomly assigned into two treatment groups with a 1:1 ratio and followed for 52 weeks from the first dose. The primary endpoint of the study is the increase of forced vital capacity (FVC) at 52 weeks. Secondary endpoints include high-resolution computed tomography (HRCT), diffusion capacity for carbon monoxide of the lung (DLCO), the Mahler dyspnea index, the health-related quality of life (HARQoL) score, the cough symptom score, EULAR Sjögren's syndrome disease activity index (ESSDAI), and safety.DiscussionThis study will be the first randomized controlled trial to investigate tofacitinib compared to the traditional regimen of CYC in combination with AZA in the treatment of pSS-ILD, which will provide data on efficacy and safety and further elucidate the role of the JAK-STAT signaling pathway in the development of pSS-ILD.Ethics and disseminationBefore starting the experiment, the research proposal, informed consent (ICF) and relevant documents in accordance with the ethical principles of the Helsinki Declaration and the relevant requirements of the local GCP rules for ethical approval shall be submitted to the ethics committee of the hospital. The ethical approval of this study is reviewed by the Ethics Committee of Tongji Hospital and the ethical approval number is 2021-LCYJ-007. When the experiment is completed, the results will also be disseminated to patients and the public through publishing papers in international medical journals.Trial registrationThe study was registered on the Chinese Clinical Trial Registry, www.chictr.org.cn; ID ChiCTR2000031389.

Efficacy and safety of remibrutinib, a selective potent oral BTK inhibitor, in Sjögren’s syndrome: results from a randomised, double-blind, placebo-controlled phase 2 trial

ObjectivesTo evaluate the safety and efficacy of remibrutinib in patients with moderate-to-severe Sjögren’s syndrome (SjS) in a phase 2 randomised, double-blind trial (NCT04035668; LOUiSSE (LOU064 in Sjögren’s Syndrome) study).MethodsEligible patients...

A single-center study of clinical features of pediatric Sjögren’s syndrome

ObjectiveSjögren’s syndrome (SS) is a rare disease with unclear diagnostic criteria among the children and adolescents. The purpose of this study is to describe the clinical features of pediatric Sjögren’s syndrome and validate with Japanese diagnostic guidelines criteria of 2018.MethodsWe conducted a retrospective analysis of the clinical data of a cohort of 54 patients with pediatric Sjögren’s syndrome admitted to our hospital over a total of 10 years from September 2013 to September 2022.ResultsThe ratio of females to males was 49:5 among the 54 children (34 cases of primary SS and 20 cases of secondary SS), the average age of onset of symptoms for the first time was 9.9 years, and the average age at diagnosis was 10.2 years. In terms of subjective symptoms, 7 cases (13.0%) presented with dry mouth and 5 cases (9.3%) reported dry eyes. The positive rates were 9.3% for Schirmer I test, 70.4% for salivary gland function test, and 55.6% for salivary gland ultrasonography. The positive rates were 94.4% for Anti-Ro/SSA antibodies, 66.7% for Anti-La/SSB antibodies, 88.9% for ANA, 59.3% for RF, and the elevation rate of IgG was 63.0%. Among the EULAR Sjögren’s syndrome disease activity index (ESSDAI) domains, the biological, constitutional, glandular, cutaneous, and lymphadenopathy domains were most involved. Treatment consisted of glucocorticoids in 88.9% of the patients in our study and hydroxychloroquine in 92.6%. As per the Japanese version of the clinical practice guidance for Sjögren’s Syndrome in pediatric patients (2018), 5 cases were identified as Definite SS, 35 cases as Probable SS, and 14 cases as Possible SS. With respect to primary and secondary SS, there was essentially no significant difference between the groups in any of the above aspects.ConclusionsPatients with pediatric SS presented with a wide spectrum of clinical features, a low prevalence of reported symptoms of dry mouth and dry eyes, and various clinical manifestations with multi-system involvement. These are similar to other pediatric study cohorts in terms of epidemiology, auxiliary investigation results, disease activity scores, and treatment. The coincidence between our study and the Japanese version of the clinical practice guidance for Sjögren’s Syndrome in pediatric patients (2018) is good for the diagnosis of pediatric SS.

14-3-3η Proteins as a Diagnostic Marker, Disease Activation Indicator, and Lymphoma Predictor in Patients with Primary Sjögren Syndrome.

Primary Sjögren syndrome (PSS) is a chronic, autoimmune, and lymphoproliferative disease of the connective tissue. In patients with PSS, the risk of developing B-cell non-Hodgkin lymphoma (NHL) increases dramatically, with a prevalence of approximately 5%. The 14-3-3 protein isoforms are phospho-serin/phospho-threonine binding proteins associated with many malignant diseases. This study aimed to evaluate the relationship between disease activity parameters and markers predicting lymphoma development in patients with PSS and 14-3-3η proteins. This study was designed as an analytical case-control study. A total of 57 PSS patients and 54 healthy volunteers were included in the study. The European League Against Rheumatism (EULAR) Sjögren syndrome disease activity index (ESSDAI) was used to assess systemic disease activity in PSS. Receiver operating characteristic (ROC) analysis was used to test the diagnostic accuracy measures of the analytical results. Multivariable linear regression analysis was used to evaluate the effects of independent variables on the 14-3-3η protein. The 14-3-3η protein serum levels were found to be significantly higher in PSS (2.72 [2.04-4.07]) than healthy controls (1.73 [1.41-2.43]) (P<0.0001). A significant relationship was found between 14-3-3η protein levels and ESSDAI group (β=0.385, 95%CI=0.318-1.651, P=0.005), hypocomplementemia (C3 or C4) (β=0.223, 95% CI=0.09-1.983, P=0.048) and purpura (β=0.252, 95% CI=0.335-4.903, P=0.022), which are accepted as lymphoma predictors. A significant correlation was found between PSS disease activity score ESSDAI and 14-33η protein (β=0.496, 95% CI=0.079-0.244, P=0.0002). 14-3-3η proteins are potential candidates for diagnostic marker, marker of disease activity, and predictor of lymphoma in PSS patients.

EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) and Other Patient-Reported Outcomes in the Assessment of Glandular Dysfunction in Primary Sjögren's Syndrome.

The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI), and other patient-reported outcomes (PROs), such as the visual analog scale (VAS) for symptoms and EULAR sicca score (ESS), are used to assess the disease activity of primary Sjögren's syndrome (pSS). Recently, Clinical ESSDAI (ClinESSDAI) and Clinical Trials ESSDAI (ClinTrialsESSDAI) were developed for objective clinical disease activity indexes. However, the relationship of ClinESSDAI and ClinTrialsESSDAI with PROs as well as that between ESSPRI and other PROs and the objective parameters of glandular function in pSS have not been established. Herein, we investigated the correlation of ESSPRI and other PROs with the objective parameters of glandular function and the relationship of PROs with ClinESSDAI and ClinTrialsESSDAI in 66 patients with pSS. Correlations were calculated with Spearman's correlation coefficient. ClinTrialsESSDAI was correlated with ESSPRI, dryness (ESSPRI-Dryness), fatigue, and pain domains of ESSPRI, VAS for oral dryness (oral-VAS), and patient's global assessment. Although ESSPRI did not correlate with the objective parameters of glandular function, ESSPRI-Dryness, ESS, and oral- and ocular-VAS did. These results suggest that ESSPRI-Dryness, ESS, and VAS for symptoms, but not ESSPRI, reflect the glandular dysfunction and that ClinTrialsESSDAI correlates with PROs for dryness in pSS.

Association of Inflammatory Cytokine Levels with Extra Glandular Manifestations, Fatigue, and Disease Activity in Primary Sjögren's Syndrome in Saudi Patients: A Cross-Sectional Study.

Primary Sjögren's syndrome (pSS) is an autoimmune disease that can cause fatigue and extraglandular manifestations (EGMs). pSS is associated with cytokine network dysregulation, which may be related to the immune-mediated destruction of exocrine glands. We determined cytokine levels and their relationship to EGMs, the European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI), and fatigue in Saudi patients with pSS. This study was a cross-sectional, single-center study. We included forty-one patients and 71 controls. Serum samples were collected from random healthy people and pSS patients who were followed in the rheumatology and pulmonary clinics of King Saud University Medical City in Riyadh, Saudi Arabia. Levels of the frequently studied cytokines were measured using Luminex xMAP technology. Each ESSDAI score and EGM were recorded, and the Arabic version of the fatigue severity scale (FSS) was applied to assess fatigue. The main outcome measures were cytokine levels in pSS Saudi patients using/not using immune-suppressive medications (ISMs). Thirty-six (87.8%) patients had one or more EGMs, and the mean ESSDAI score was 9.95 ± 7.73. There was a significant decrease in TNFα and IL-21 levels in the pSS group compared to those in the control group (p = 0.034 and p < 0.001, respectively), whereas IL-12 levels were significantly elevated in the pSS group (p = 0.002). Cytokine levels in patients who used ISMs were the same as those in patients who did not use medications. Decreased IL-1β (p = 0.014), IL-2 (p = 0.035), IL-6 (p = 0.014), and IL-35 (p = 0.010) levels were observed in patients who had EGMs. Patients who had low disease activity exhibited low IL-10 (p = 0.018) and high IFN-α (p = 0.049), IFN-β (p = 0.049), IL-1β (p = 0.006), and IL-35 (p = 0.032) levels compared to patients with high disease activity. A negative association between a positive fatigue score and IL-1β (p = 0.010), IL-2 (p = 0.037), IFN-α (p = 0.025), TNFα (p = 0.030), IL-17 (p = 0.029), IL-12 (p = 0.046), and IL-21 (p = 0.005) levels was found. Cytokine profiles correlate with EGMs, ESSDAI, and fatigue. Patients with controlled disease activity have a normal cytokine profile that is similar to that of controls.

Endothelial Dysfunction in Primary Sjögren's Syndrome: Correlation with Serum Biomarkers of Disease Activity.

To assess the relationship between endothelial dysfunction and serum cytokines, anti-SSA and anti-SSB antibodies, beta-2 microglobulin levels, focus score and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) in primary Sjögren's syndrome (pSS) patients. The study included 90 patients with pSS and 45 healthy subjects, matched for age and gender, as controls. Serum beta-2 microglobulin, total cholesterol, HDL-cholesterol, triglycerides, TNF-α, and IL-6 were analyzed in both the groups. Patients with pSS were also tested for antinuclear antibodies, anti-SAA (anti-Sjögren's syndrome-related antigen A) antibodies, anti-SSB (anti-Sjögren syndrome related antigen B) antibodies, and focus score (the histopathologic one, based on minor salivary gland biopsy). Endothelial dysfunction was assessed by means of flow-mediated dilation (FMD) in the brachial artery. Data are presented as mean ± standard deviation. Statistical analysis was performed using the t-test and the Pearson's correlation. Differences were considered to be statistically significant if the value of p < 0.05. Endothelial dysfunction was identified in pSS patients (p < 0.00001). The serum levels of cytokines (TNF-α, respective IL-6) and beta-2 microglobulin were increased in pSS patients compared with controls (p < 0.00001). Endothelial dysfunction (expressed as FMD%) was correlated with focus score, ESSDAI, levels of anti-SSA and anti-SSB antibodies, beta-2 microglobulin, IL-6, and TNF-α, with statistical significance. Endothelial dysfunction is present in pSS patients and is associated with a high focus score and activity as well as increased concentrations of antibodies, pro-inflammatory cytokines, and beta 2-microglobulin.

Effect of adipose tissue-derived stem cells therapy on clinical response in patients with primary Sjogren’s syndrome

The purpose of this trial was to clinically assess the effect and safety of Adipose Tissue-derived Stem Cells (ADSCs) treatment on primary Sjogren’s Syndrome (pSS). In this 6-month randomized, triple-blind, placebo-controlled clinical trial, pSS patients were randomly assigned to two groups. After demographic characteristics and clinical examination were achieved, local injection of ADSCs into bilateral glands was performed with patients in ADSCs group (n = 35) and placebo solution was used for another group (n = 39) at three time points. Patients were followed up at 1-, 3- and 6-month. At each visit, studies of clinical and laboratory outcomes, as well as subjective symptoms, were conducted. A total of 74 subjects who met the including criteria were allocated in two groups and eventually 64 subjects (86.5%) completed the treatments and the follow-up assessments. Secretion of salivary and lachrymal glands were significantly improved in 3-month (P < 0.05). A great improvement of European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index (ESSDAI) was found after ADSCs treatment with intergroup comparison from baseline to follow-up (P < 0.05). There is also a significant difference of European Alliance of Associations for Rheumatology SS Patient Reported Index (ESSPRI) between the two groups in the follow-up (P < 0.05). A significant abatement of IgG, IgM, C3, C4 and ESR between two groups was observed in part of follow-up time points (P < 0.05). The ADSCs therapy can provide relief of oral and eye’s dryness in our trial in a short time and has potential improvement of subjective and systemic syndromes of pSS.