Primary Sjögren's Syndrome Patients Research Articles

Predicting the Risk of Primary Sjögren's syndrome with Key N7-methylguanosine-related Genes: A Novel XGBoost Model

ObjectivesN7-methylguanosine (m7G) plays a crucial role in mRNA metabolism and other biological processes. However, its regulators' function in Primary Sjögren's Syndrome (PSS) remains enigmatic. MethodsWe screened five key m7G-related genes across multiple datasets, leveraging statistical and machine learning computations. Based on these genes, we developed a prediction model employing the extreme gradient boosting decision tree (XGBoost) method to assess PSS risk. Immune infiltration in PSS samples was analyzed using the ssGSEA method, revealing the immune landscape of PSS patients. ResultsThe XGBoost model exhibited high accuracy, AUC, sensitivity, and specificity in both training, test sets and extra-test set. The decision curve confirmed its clinical utility. Our findings suggest that m7G methylation might contribute to PSS pathogenesis through immune modulation. Conclusionsm7G regulators play an important role in the development of PSS. Our study of m7G-realted genes may inform future immunotherapy strategies for PSS.

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.

Association of pulmonary hypertension with outcomes in patients with Systemic sclerosis and other connective tissue disorders: review and meta-analysis.

Pulmonary hypertension (PH) is a frequent complication of connective tissue disorders (CTDs), with a major impact on the prognosis of the disease. The aim of our study was to perform a systemic review and meta-analysis of published literature evaluating survival function in patients with systemic sclerosis (SSc) with and without PH and to compare survival function between patients with SSc, systemic lupus erythematosus (SLE), other CTDs, and conditions associated with PH. The established protocol of the Cochrane Collaboration Steps and meta-analysis of observational studies in epidemiology recommendations (MOOSE) were used. 7 studies, including 1470 SSc-PH patients and 1368 SSc patients without PH, and 4 studies, including 108 SLE-PH patients and 1288 SLE patients without PH, assessed survival function were selected. Six studies (including 777 SSc, 249 SLE, 90 idiopathic pulmonary arterial hypertension (IPAH) and 29 primary Sjogren's syndrome patients) comparing survival function in different subgroups of patients with confirmed PH were included. SSc patients with PH showed the worst survival as compared to SSc patients without PH [OR (95% CI) 3.70 (2.42-5.67); p<0.00001]. The same pattern was observed in patients with SLE. SSc patients with PH were characterized by lower survival function compared to other reasons for PH, including SLE [OR (95% CI) 2.76 (1.95-3.91); p<0.00001]. Patients with SSc-PH are characterized by significantly lower survival function as compared to SSc patients without PH. Among the different entities of PH, SSc shows the worst survival, underlining prognostic significance of detection and evaluation of PH according to the currently established approach.

Unveiling the age-related dynamics in Sjögren's syndrome: Insights from heart rate variability and autonomic function.

Sjögren's Syndrome (SS), mainly affecting women in their midlife, is characterized by persistent inflammation in glands producing tears and saliva, often leading to significant complications. This study investigates the differences in autonomic system functioning between individuals with SS and healthy controls. From April 2019 to December 2022, 329 diagnosed primary SS (pSS) patients and 30 healthy controls were enrolled at Taipei Veterans General Hospital, Taipei, Taiwan. The study assessed autonomic nervous system functioning using various HRV metrics. Participants were divided based on age and AECG criteria, including salivary gland biopsy and autoantibody status. Significant differences in Heart Rate Variability (HRV) were observed between pSS patients and healthy controls. The total power index was notably lower in pSS patients (4.98 ± 1.29) than in controls (5.54 ± 1.21, p = .022). Additionally, Vagal (VAG) activity was significantly reduced in the pSS group (4.95 ± 1.33) compared to the healthy control group (5.47 ± 1.19, p = .041). Age-stratified analysis highlighted that the ≤50 years pSS group had a higher heart rate (77.74 ± 10.42) compared to the >50 years group (73.86 ± 10.35, p = .005). This group also showed a higher total power index (5.78 ± 1.30) versus the >50 years group (4.68 ± 1.19, p < .001), and significantly lower VAG activity (4.70 ± 1.26, p = .007) compared to healthy controls. Furthermore, the Standard Deviation of Normal-to-Normal Intervals (SDNN) was greater in the ≤50 years SS group (44.45 ± 37.12) than in the >50 years group (33.51 ± 26.18, p = .007). In pSS patients, those positive for both salivary gland biopsy and autoantibodies demonstrated a lower Total Power (4.25 ± 1.32) and R-wave validity (93.50 ± 4.79, p < .05) than other groups, suggesting more severe autonomic imbalance. The R-R interval variation (RRIV) was also significantly higher in this dual-positive group (696.10 ± 975.41, p < .05). Additionally, the ESSPRI for dryness was markedly higher in the dual-positive group (8.10 ± 1.45, p < .05), indicating more severe symptoms. These findings reveal significant variations in autonomic function in SS patients, especially in those with dual-positive biopsy and autoantibody status. This study demonstrates significant autonomic dysfunction in pSS patients compared to healthy controls, particularly in those positive for both salivary gland biopsy and autoantibodies. The age-stratified analysis further emphasizes the impact of aging on autonomic system functioning in pSS, suggesting a need for age-specific management approaches in pSS patient care.

Choroidal, retinal, and optic nerve changes in rheumatoid arthritis and primary sjogren's syndrome patients: comparıson with each other and healthy subjects.

The present study aims to evaluate the optic nerve, macula, and choroidal changes in both rheumatoid arthritis (RA) and primary Sjögren's syndrome (SjS) patients, and to compare these findings with age-matched healthy volunteers. This study included 46 RA patients, 33 primary SjS patients, and 37 age-matched healthy volunteers. All of the patients underwent a thorough ophthalmological examination, during which measurements of the retinal nerve fiber layer (RNFL), ganglion cell layer(GCL), and subfoveal choroidal thickness (CT) were taken using OCT (optical coherence tomography). The measurements taken from the right eye of each patient were used to compare among the groups. RNFL thickness in superior quadrant was found to be statistically significantly thinner in the eyes with RA when compared to the control group (p = 0.022). In the nasal quadrant, the RNFL thickness was significantly thinner in patients with primary SjS compared to healthy individuals (p = 0.036). Also, the temporal quadrant RNFL was significantly thinner in RA patients than in the primary SjS patients (p = 0.033). GCL thickness was observed to be thinner in all quadrants of both RA and primary SjS groups compared to the control group. However, the difference was not found to be statistically significant. Subfoveal CT was observed to be thicker in RA and SjS groups compared to the control group, but this difference was also not statistically significant. Systemic autoimmune diseases like RA and primary SjS can lead to a decrease in RNLF and GCL thickness, which can impair visual acuity even in the absence of ocular symptoms. Therefore, monitoring changes in the optic nerve, retina, and choroid layer are crucial in these patients.

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.

Comparison between 100% autologous serum and 100% platelet‐rich plasma eye drops and their impact on the treatment efficacy of dry eye in primary Sjogren syndrome

Purpose: The aim of the study was to compare the difference in the composition of 100% autologous serum (AS) and 100% platelet‐rich plasma (PRP) eye drops and assess their impact on the clinical out‐comes after the treatment of severe dry eye (DE) in primary Sjogren Syndrome patients (pSS).Methods: 22 patients with severe DE in pSS were treated with 100% AS (22 eyes) and 100% PRP (22 eyes) eye drops 5 times per day as monotherapy. The quantification of growth factors (GFs) as fibroblast growth factor (FGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet‐derived growth factor (PDGF), nerve growth factor (NGF), transforming growth factor (TGF‐b), insulin‐like growth factor(IGF), fibronectin and substance P in hemoderivates was performed. The main outcomes: Ocular Surface Disease Index (OSDI), Best Corrected Visual Acuity (BCVA), the Schirmer test, tear break‐up time (TBUT), corneal and conjunctival staining according to the Oxford scale, conjunctival hyperaemia and Meibomian gland parameters. The results were compared at the baseline, 1 and 3 months after the treatment. The clinical results were correlated with the concentration of GFs.Results: Significant differences were observed in the concentration of FGF, EGF, fibronectin, VEGF, PDGF AB, NGF, PDGF, substance P, TGF‐β in PRP compared to AS. There was a statistically significant improvement in BCVA, the Schirmer test, TBUT, Meibomian gland parameters, and the reduction of the OSDI scores, Oxford staining and conjunctiva hyperaemia in each group. There were many correspondences between the level of GFs and the mean change of the clinical outcomes. No adverse events were reported.Conclusions: Despite the fact that blood derivatives differ in their composition, they seem to be effective, safe in the treatment of severe DE in pSS patients. The signs and symptoms of DE were reduced in both groups. The obtained clinical results and the composition of hemoderivates may indicate the superiority of PRP in relieving the signs and symptoms of DE in pSS patients.

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.

Clinical significance of the expression levels of serum transforming growth factor-β and CXC type chemokine ligand 13 in primary Sjogren's syndrome patients.

The aim of this study was to investigate the expression levels of the serum transforming growth factor-β1 (TGF-β1) CXC type chemokine ligand 13 (CXCL13) in primary Sjogren's syndrome (pSS) patients and its correlation with disease severity. Thirty patients with pSS admitted to Nanjing Traditional Chinese Medicine Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from January 2021 to December 2022 were included as the pSS group, while 30 patients who underwent physical examination during the same period were included as the control group. The levels of TGF-β1 and CXCL13 were detected. The diagnostic value of TGF-β1 and CXCL13 for pSS was analyzed. Detection of serum TGF-β1 and CXCL13 levels in pSS patients with different disease activities and lip gland pathological grading of pSS was done. We compared the correlation between TGF-β1 and CXCL13 levels and disease activity and labial gland pathological grading in pSS patients. The TGF-β1 and CXCL13 levels in the pSS group were higher than those in the control group. The area under the receiver operating characteristic (ROC) curve (AUC) for TGF-β1 and CXCL13 diagnosis of pSS was 0.790 (95% confidence interval (CI): 0.720~0.861) and 0.838 (95% CI: 0.778~0.898), respectively. The serum TGF-β1 and CXCL13 levels of pSS patients significantly increase with the increase of disease activity and lip gland pathological grading. The TGF-β1 and CXCL13 levels in pSS patients were positively correlated with disease activity and lip gland pathological grading. The levels of TGF-β1 and CXCL13 in pSS patients were increased, and it was closely related to disease activity and lip gland pathological grading, which can be used as an effective indicator for the diagnosis of pSS. Key Points • The TGF-β1 and CXCL13 levels in the pSS group were higher than those in the control group. • The TGF-β1 and CXCL13 levels in pSS patients were positively correlated with disease activity and lip gland pathological grading. • TGF-β1 and CXCL13 can be used as an effective indicator for the diagnosis of pSS.

Environmental Effects on Dry Eyes in Primary Sjogren&amp;apos;s Syndrome

Purpose: To investigate the effects of humidity, temperature, and fine particulate matter (PM&lt;sub&gt;2.5&lt;/sub&gt;) on dry eye disease (DED) parameters in primary Sjogren's syndrome patients.Methods: We retrospectively analyzed the medical records of 18 primary Sjogren's syndrome patients who underwent DED treatment and had more than two follow-up visits. Symptom Assessment in Dry Eye (SANDE) scores, tear secretion, tear film breakup times, ocular surface staining scores, and tear osmolarity were assessed. Temperature, humidity, and PM&lt;sub&gt;2.5&lt;/sub&gt; concentrations during the week before the patient visits were calculated using public data and their relationships with DED parameters were analyzed.Results: All patients were females, with an average age of 57.6 ± 12.4 years. High temperature was significantly correlated with humidity and PM&lt;sub&gt;2.5&lt;/sub&gt; concentration (&lt;i&gt;p&lt;/i&gt; = 0.004 and = 0.006, respectively). The high humidity, high temperature, and low PM&lt;sub&gt;2.5&lt;/sub&gt; groups had lower SANDE scores (&lt;i&gt;p&lt;/i&gt; = 0.017, = 0.063, and = 0.049, respectively) and tear osmolarity (&lt;i&gt;p&lt;/i&gt; &lt; 0.001, = 0.009, and &lt; 0.001, respectively). Multiple regression analysis showed that temperature and humidity had stronger correlations with tear osmolarity (&lt;i&gt;p&lt;/i&gt; = 0.005 and = 0.012, respectively) compared to PM&lt;sub&gt;2.5&lt;/sub&gt; concentrations.Conclusions: Ocular discomfort and tear osmolarity were correlated with temperature, humidity, and PM&lt;sub&gt;2.5&lt;/sub&gt; concentrations. Among the DED parameters, tear osmolarity was the most sensitive indicator of exposure to environmental factors.

Association Between Bruton's Tyrosine Kinase Gene Overexpression and Risk of Lymphoma in Primary Sjögren's Syndrome.

We undertook this study to analyze whole blood gene expression and to investigate the role of B cell genes in primary Sjögren's syndrome-related non-Hodgkin lymphoma (primary SS-NHL). Peripheral whole blood samples were collected from 345 well-phenotyped patients with primary SS enrolled in the prospective Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort. Transcriptomic analysis was performed using human Clariom S Arrays (Affymetrix). In our primary analysis, we considered patients with incident lymphoma (i-primary SS-NHL) as the case group and all patients without lymphoma as the comparison group. In our sensitivity analyses, we considered all patients with primary SS-NHL, including those with a history of lymphoma (h-primary SS-NHL), as the case group and primary SS patients without lymphoma, stratified on their risk factors of lymphoma, as the comparison group. Twenty-one patients with primary SS-NHL (including 8 with i-primary SS-NHL and 13 h-primary SS-NHL) were eligible for transcriptomic analysis; we compared these patients to 324 primary SS controls without lymphoma, including 110 with moderate to severe disease activity and 61 with no risk factor of lymphoma. Functional clustering analyses revealed an enrichment of genes related to innate and adaptive immunity, including B cell-related genes. Bruton's tyrosine kinase (BTK) and a proliferation-inducing ligand (APRIL) genes were overexpressed before the occurrence of lymphoma in patients with incident lymphoma compared with patients without lymphoma. In sensitivity analyses, BTK was consistently up-regulated across all comparisons performed. BTK expression was associated with risk of lymphoma on multivariate analyses, which considered 9 validated predictors of lymphoma in primary SS. BTK and APRIL were overexpressed in the peripheral blood of primary SS patients prior to lymphoma. The association between BTK, APRIL, and primary SS-NHL requires confirmation in other prospective cohorts.

Phenotypic and proteomic analysis of plasma extracellular vesicles highlights them as potential biomarkers of primary Sjögren syndrome.

Sjögren syndrome (SjS) is an autoimmune disease characterized by the destruction of the exocrine gland epithelia, causing a dryness of mucosa called sicca symptoms, and whose main life-threatening complication is lymphoma. There is a need for new biomarkers in this disease, notably diagnostic biomarkers for patients with genuine sicca symptoms that do not meet current criteria, and prognostic biomarkers for patients at risk of lymphoma. Plasma extracellular vesicles (EVs) are promising biomarker candidates in several diseases, but their potential has not yet been explored in SjS. In this proof-of-concept study, we characterized EVs from primary SjS patients (pSS, n=12) at the phenotypic and proteomic levels, compared to EVs from healthy donor (HD, n=8) and systemic lupus erythematosus patients (SLE, n=12). Specific plasma EVs subpopulations, derived from neutrophils, endothelial, and epithelial cells, were found increased in pSS. We also identified a pSS proteomic signature in plasma EVs, including neutrophil-, epithelial-, and endothelial-related proteins, such as integrin alpha M (ITGAM), olfactomedin-4 (OLFM4), Ras-related protein RAB10, and CD36. Overall, our results support the relevance of plasma EVs as biomarkers in SjS.

Diagnostic role of CXCL13 biomarker in primary Sjogren's syndrome patients with parotid non-Hodgkin's lymphoma complication

IntroductionSerum biomarkers are important predictive factors for development of parotid non-Hodgkin's lymphoma (NHL) complication in primary Sjogren's syndrome (pSS) patients. The aim was to evaluate the diagnostic accuracy of serum CXCL13 chemokine in pSS patients with parotid NHL complication. Material and methodsSerum CXCL13 chemokine was assessed in 33 patients with pSS [7 with parotid NHL complication (pSS+NHL subgroup) and 26 without NHL (pSS-NHL subgroup)] and 30 healthy subjects. ResultsThe serum CXCL13 levels in pSS+NHL subgroup [175.2 (107.9–220.4) pg/ml] were significantly higher comparing to the healthy subjects group (p=0.018) and the pSS-NHL subgroup (p=0.048). A cut-off value of 123.45pg/ml (Se=71.4%, Sp=80.8%, AUROC=0.747) was established for parotid lymphoma diagnosis. ConclusionThe serum CXCL13 biomarker could be considered a valuable tool for the diagnosis of parotid NHL complication in pSS patients.

The Comparison between the Composition of 100% Autologous Serum and 100% Platelet-Rich Plasma Eye Drops and Their Impact on the Treatment Effectiveness of Dry Eye Disease in Primary Sjogren Syndrome.

The aim of the study was to compare the difference in composition between 100% autologous serum (AS) and 100% platelet-rich plasma (PRP) eye drops and assess their impact on the clinical outcomes after the treatment of severe dry eye (DE) in primary Sjogren Syndrome patients (pSS). This is an interventional, non-randomized, comparative, three-month study. 22 patients with severe DE in pSS were treated with 100% AS (22 eyes) and 100% PRP (22 eyes) eye drops 5 times per day in monotherapy mode. The quantifications of growth factors (GFs) such as fibroblast growth factor (FGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), nerve growth factor (NGF), transforming growth factor (TGF-b), insulin-like growth factor (IGF), fibronectin, and substance p in hemoderivates were done. The main outcome measures were: Ocular Surface Disease Index (OSDI), Best Corrected Visual Acuity (BCVA), the Schirmer test, tear break-up time (TBUT), corneal and conjunctival staining according to the Oxford scale, conjunctival hyperaemia, and Meibomian gland parameters. The results were compared at baseline, 1 month, and 3 months following the treatment. The clinical results were correlated with the concentration of GFs in the biological tear substitutes. Significant differences were observed in the concentration of FGF (4.42 ± 0.86 vs. 15.96 ± 7.63, p < 0.0001), EGF (4.98 ± 0.97 vs. 39.06 ± 20.18, p < 0.0001), fibronectin (929.6 ± 111.5 vs. 823.64 ± 98.49, p = 0.0005), VEGF (175.45 ± 65.93 vs. 717.35 ± 488.15, p < 0.0001), PDGF AB (619.6 ± 117.30 vs. 349.66 ± 79.82, p < 0.0001), NGF (85.22 ± 23.49 vs. 8.29 ± 9.06, p < 0.0001), PDGF (935.38 ± 434.26 vs. 126.66 ± 54.41, p < 0.0001), substance p (112.58 ± 27.28 vs. 127.51 ± 26.56, p = 0.0125) in PRP compared to AS. The level of TGF-β was undoubtedly higher in AS than in PRP (1031.37 ± 330.23 vs. 726.03 ± 298.95, p = 0.0004). No significant differences between AS and PRP were observed in the concentration of IGF. Therapy with blood products relieved the signs and symptoms in pSS DE patients. There was a statistically significant improvement in BCVA, the Schirmer test, TBUT, Meibomian gland parameters, and the reduction of the OSDI scores, Oxford staining, and conjunctiva hyperaemia in each of the groups. However, the clinical changes were more significant in the PRP group. There were numerous correlations between the level of GFs and the mean change in clinical outcomes. No adverse events were reported. Despite the fact that blood derivatives differ in composition, they seem to be effective and safe in the treatment of severe DE in pSS patients. The signs and symptoms of DE were reduced in both groups, but only the mean change in OSDI was statistically significant. A greater reduction in OSDI scores was observed in the PRP group. The obtained results and the composition of haemoderivates may indicate the superiority of PRP in relieving the symptoms of DE in pSS patients compared to AS.

Diagnostic role of CXCL13 biomarker in primary Sjogren's syndrome patients with parotid non-Hodgkin's lymphoma complication

IntroductionSerum biomarkers are important predictive factors for development of parotid non-Hodgkin's lymphoma (NHL) complication in primary Sjogren's syndrome (pSS) patients. The aim was to evaluate the diagnostic accuracy of serum CXCL13 chemokine in pSS patients with parotid NHL complication. Material and methodsSerum CXCL13 chemokine was assessed in 33 patients with pSS [7 with parotid NHL complication (pSS+NHL subgroup) and 26 without NHL (pSS-NHL subgroup)] and 30 healthy subjects. ResultsThe serum CXCL13 levels in pSS+NHL subgroup [175.2 (107.9–220.4) pg/ml] were significantly higher comparing to the healthy subjects group (p=0.018) and the pSS-NHL subgroup (p=0.048). A cut-off value of 123.45pg/ml (Se=71.4%, Sp=80.8%, AUROC=0.747) was established for parotid lymphoma diagnosis. ConclusionThe serum CXCL13 biomarker could be considered a valuable tool for the diagnosis of parotid NHL complication in pSS patients.

Association of Circulating Antibody-Secreting Cell Maturity With Disease Features in Primary Sjögren's Syndrome.

B cell hyperactivity plays an important role in primary Sjögren's syndrome (SS). We undertook this study to better understand the B cell effector branch, namely antibody-secreting cells (ASCs) in primary SS, and to examine the quantity, maturity, and inflammatory properties of ASCs in primary SS patients. Circulating ASCs, defined as CD3-CD14-CD27+CD38++ cells, from 21 primary SS patients and 10 healthy controls were assessed using spectral flow cytometry. Expression levels of relevant ASC markers relating to maturity, survival, and inflammatory status were analyzed using a t-distributed stochastic neighbor embedding approach. Correlation of ASC properties with primary SS disease parameters was assessed. ASCs were more abundant in peripheral blood from primary SS patients than from healthy controls (mean ± SD 3.1 ± 5.1 cells/μl versus 1.1 ± 1.0 cells/μl, respectively; P=0.048) and displayed a more mature phenotype (mean ± SD CD19- ASCs 0.37 ± 1.21 cells/μl versus 0.06 ± 0.11 cells/μl, respectively; P=0.005). An inflammatory CXCR3+ phenotype of ASCs correlated positively with our newly developed ASC maturity index (r=0.568, P=0.007) but correlated negatively with antiinflammatory interleukin-10 expression (r=-0.769, P < 0.001). ASCs with a higher maturity index also demonstrated higher levels of the pro-survival protein myeloid cell leukemia 1 (r=0.567, P=0.007). Frequency and/or maturity of ASCs correlated with several primary SS disease parameters, such as antinuclear antibody and anti-La/SSB titers, salivary gland focus scores, and ocular staining scores. Quantity and maturity of ASCs in primary SS patients are increased and correlate with disease parameters. A higher maturity index of ASCs marks a pro-survival and proinflammatory phenotype. Altogether, B cell hyperactivity in primary SS extends to the peripheral ASC compartment, raising potential for ASCs as future biomarkers or targets for primary SS treatment.

Salivary Flow Rate and Oral Status in Patients with Primary Sjögren's Syndrome and Diffuse Cutaneous Systemic Sclerosis: A Cross-Sectional Study.

Determination of salivary flow rate and oral status in patients with primary Sjögren's Syndrome (pSS) and diffuse cutaneous systemic sclerosis (dcSSc) and comparison with control subjects. Thirty-one pSS patients, 28 dcSSc patients, and 28 control subjects participated in this single-center, cross-sectional study. Unstimulated whole salivary flow rate (UWSFR) and stimulated whole salivary flow rate (SWSFR), salivary pH, DMFT index (D-decayed, M-missing, F-filled tooth), periodontal pocket depth (PPD), clinical attachment level (CAL), interincisal distance, and OHRQoL (oral health-related quality of life) were analyzed in all three groups of subjects. Primary SS and dcSSc patients had statistically significant lower values of UWSFR (0.20; 0.38 vs. 0.91 mL/min) and SWSFR (0.56; 0.70 vs. 1.64 mL/min) compared with control subjects (p < 0.001, Kruskal-Wallis test). Salivary pH values were statistically significantly lower in pSS and dcSSc patients compared with control subjects (6.00; 6.25 vs. 7.00, respectively) (p < 0.001, Kruskal-Wallis test). The DMFT index of dcSSc patients was higher (28.50) and statistically significant compared to control subjects (20.00) (p = 0.01). The prevalence of periodontitis was the same in pSS and dcSSc patients and control subjects (p = 0.384). Primary SS and dcSSc patients had a statistically significant decreased interincisal distance compared to control subjects (43.80; 38.00 vs. 48.00) (p = 0.003 and p < 0.001, respectively). Primary SS and dcSSc patients show decreased UWSFR and SWSFR, salivary pH values closer to an acidic medium, higher DMFT index, higher prevalence of periodontitis, decreased interincisal distance, and poorer OHRQoL, i.e., poor oral and periodontal health.

Biomedical statistics study on the correlation between peripheral blood follicular helper T cell subsets and primary Sjogren's syndrome.

To study the expressions of follicular helper T cell (Tfh) subsets--Tfh1, Tfh2, and Tfh17, in peripheral blood (PB) of primary Sjogren's syndrome (PSS) patients in the active phase and remission period after treatment, and to analyze the pathogenic effects of Tfh subsets in PSS patients. The proportions of Tfh1, Tfh2, and Tfh17 were measured by flow cytometry in the healthy group, PSS patients group, active phase group, and remission phase group. Enzyme-linked immunosorbent assay was used to detect IL-21 expression in SS patients in active and remission stages. Biomedical statistics was used to analyze the correlation between Tfh subsets and SS disease activity index; and analyze the correlation between the proportions of Tfh subsets in the healthy group, primary group, active stage, and remission stage In contrast with the healthy group, the levels of Tfh1, Tfh2, and Tfh17 in CD4+ T cells of PSS patients were prominently reduced. PSS patients in the active phase had significantly lower Tfh1, Tfh2, and Tfh17 levels but remarkably higher IL-21 levels than in the remission phase. The contents of Tfh1, Tfh2, and Tfh17 are negatively correlated with the severity of PSS.

FDG-PET/CT discriminates between patients with and without lymphomas in primary Sjögren's syndrome.

To assess the usefulness of [18F]-fluorodeoxyglucose (FDG)-PET/CT (i) to discriminate between primary SS (pSS) patients with and without lymphomas and (ii) to evaluate systemic disease activity in pSS. ACR-EULAR-positive pSS patients who underwent FDG-PET/CT were included. Scans were visually evaluated and quantitative analysis was performed by measuring standardized uptake values (SUV) of salivary and lacrimal glands and systemic regions. Receiver operating characteristic curve analyses were performed to find SUV cut-off values to discriminate between lymphoma and non-lymphoma. Of the 70 included patients, 26 were diagnosed with a pSS-associated lymphoma, mostly of the mucosa-associated lymphoid tissue type (23/26). Lymphoma patients showed higher FDG uptake in the parotid and submandibular glands, and more frequently showed presence of nodular lung lesions, compared with non-lymphoma patients. The accuracy of the maximum SUV (SUVmax) in the parotid and submandibular gland to predict lymphoma diagnosis was good, with optimal cut-off points of 3.1 and 2.9. After combining these three visual and quantitative findings (nodular lung lesions, parotid SUVmax > 3.1 and submandibular SUVmax > 2.9), sensitivity was 92% when at least one of the three features were present, and specificity was 91% in case at least two features were present. Furthermore, FDG-PET/CT was able to detect systemic manifestations in pSS patients, mostly involving lymph nodes, entheses and lungs. FDG-PET/CT can assist in excluding pSS-associated lymphomas in patients without PET abnormalities, possibly leading to a decrease of invasive biopsies in suspected lymphoma patients. Furthermore, FDG-PET/CT is able to detect systemic manifestations in pSS and can guide to the best biopsy location.

Analysis of clinical features and risk factors of peripheral neuropathy in patients with primary Sjögren's syndrome

ObjectiveTo observe the clinical features and efficacy of immunosuppressive therapy in patients with primary Sjögren's syndrome (PSS) combined with peripheral neuropathy (PN) syndrome and to explore the risk factors for PN in patients with PSS.MethodsSixty consecutive patients with PSS admitted to the Department of Rheumatology and Immunology, Wuhan No. 1 Hospital, from January 2014 to June 2020 were analysed retrospectively. Patients were divided into a PN group (N = 15) and a non-PN group (N = 45). The clinical characteristics of the two groups were compared, and the independent risk factors for PN combined with PSS were analysed by multivariate logistic regression. The patients with PSS combined with PN were followed up to observe the effect of immunosuppressive therapy.ResultsThe patients with PN had a longer course of disease than those without PN (z = − 3.225, P = 0.001), and the incidence of Raynaud's phenomenon, anti-SSB antibody, rheumatoid factor and hyperglobulinaemia was higher (all P < 0.05) in patients with PN than in those without PN. Multivariate logistic regression analysis showed that hyperglobulinaemia, RF and anti-SSB antibodies were independent risk factors for PN with PSS (P < 0.05). Fourteen patients with PSS-PN were treated with immunosuppressants. The clinical symptoms of 10 patients were relieved, and mRS scores of 10 patients were decreased.ConclusionPN is a common complication in PSS patients. Patients with PSS combined with PN have a longer course of disease and a significantly higher percentage of Raynaud's phenomenon, positive anti-SSB antibody, positive RF and hyperglobulinaemia. Immunosuppressive therapy was effective for partial remission of PN with PSS.