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Objective: To evaluate the effect of neuropathic pain on lower urinary tract symptoms (LUTS) scores in patients with primary Sjögren's syndrome (pSS). Methods: Seventy-two patients diagnosed with pSS were included in the study. The patients with pSS were divided into two groups according to the presence/absence of neuropathic pain. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) questionnaire was recorded assess neuropathic pain. LUTS was evaluated using the International Prostate Symptom Score (IPSS), International Incontinence Consultation Questionnaire Short Form (ICIQ-SF) and Overactive Bladder Questionnaire (OAB-V8). Results: The mean age of the patients was 52.4 ± 11.2 years. Neuropathic pain was recorded in 21 (29.2%) patients. Among the patients, the number of patients with mild symptoms was recorded as 41 (56.9%), moderate symptoms in 25 (34.7%), and severe symptoms in 6 (8.3%) according to IPSS. IPSS and IPSS voiding subscores were statistically significantly higher in patients with neuropathic pain than non-neuropathic pain group (p = 0.035; p = 0.001, respectively). Although ICIQ-SF, OAB-V8 and IPSS storage subscores were found to be higher in patients with neuropathic pain group, there was no statistically significant difference between the groups (p = 0.299; p = 0.283; p = 0.237, respectively). Conclusion: Neuropathic pain concomitant with PSS patients may negatively affect bladder voiding functions. [ABSTRACT FROM AUTHOR]

Background: Progressive pulmonary fibrosis (PPF) has been associated with a worse prognosis, even when interstitial lung disease (ILD) is related to rheumatic diseases. Since many differences are detectable among rheumatic diseases in prevalence and features of ILD, we aimed to investigate features of PPF in different rheumatic diseases, namely rheumatoid arthritis (RA) and primary Sjogren's syndrome (pSS). Methods: In an Italian multicentre cross-sectional study, consecutive pSS or RA patients with a diagnosis of ILD from at least two years were enrolled. For each patient, demographic, clinical, and serological data, other than chest high-resolution computed tomography and lung function tests, were recorded at the enrolment and after 2 years. Results: Among 232 patients, namely 156 RA-ILD and 76 pSS-ILD, a PPF was recorded in 38.8% of cases, without differences between the two diseases. Analysing patients with a PPF, usual interstitial pneumonia was significantly more frequent in RA than pSS (71.4% and 44.4%, respectively; p = 0.019), while ILD preceded the diagnosis of the rheumatic disease in 29.1% of RA and 89.5% of pSS (p < 0.001). Finally, RA patients were significantly younger than pSS at the diagnosis of the rheumatic disease (p < 0.001). Conclusions: In conclusion, although there is a similar prevalence of PPF in RA-ILD and pSS-ILD, we demonstrated for the first time that the two conditions differ in terms of radiological patterns and demographic and clinical features, suggesting that specific factors related to such diseases might influence the lung involvement over time. Prospective studies could investigate if these specificities could induce different responses to the treatment. [ABSTRACT FROM AUTHOR]

Abstract Objective To evaluate the effect of neuropathic pain on lower urinary tract symptoms (LUTS) scores in patients with primary Sjögren’s syndrome (pSS). Methods Seventy-two patients diagnosed with pSS were included in the study. The patients with pSS were divided into two groups according to the presence/absence of neuropathic pain. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) questionnaire was recorded assess neuropathic pain. LUTS was evaluated using the International Prostate Symptom Score (IPSS), International Incontinence Consultation Questionnaire Short Form (ICIQ-SF) and Overactive Bladder Questionnaire (OAB-V8). Results The mean age of the patients was 52.4 ± 11.2 years. Neuropathic pain was recorded in 21 (29.2%) patients. Among the patients, the number of patients with mild symptoms was recorded as 41 (56.9%), moderate symptoms in 25 (34.7%), and severe symptoms in 6 (8.3%) according to IPSS. IPSS and IPSS voiding subscores were statistically significantly higher in patients with neuropathic pain than non-neuropathic pain group (p = 0.035; p = 0.001, respectively). Although ICIQ-SF, OAB-V8 and IPSS storage subscores were found to be higher in patients with neuropathic pain group, there was no statistically significant difference between the groups (p = 0.299; p = 0.283; p = 0.237, respectively). Conclusion Neuropathic pain concomitant with PSS patients may negatively affect bladder voiding functions.

Objective To investigate the correlation between salivary cystatin D level and salivary gland injury in patients with primary Sjögren syndrome (pSS). Methods A total of 51 pSS patients admitted in the Department of Rheumatology and Immunology of the First Affiliated Hospital of Xi'an Jiaotong University from September 1, 2022 to June 30, 2023, and 51 age- and gender-matched healthy individuals who took physical examination in the hospital during same period were enrolled in the study. The level of salivary cystatin D was detected, and the difference in the level between the 2 groups was compared using an independent-samples t test. Pearson correlation analysis was applied to analyze the correlation between salivary cystatin D and clinical parameters in the patients. Results The pSS patients had significantly lower cystatin D level than the healthy controls (206.55±108.11 vs 374.32±172.24 pg/mL, P < 0.01). The cystatin D level in the pSS patients was positively correlated with both static (r=0.433, P=0.002) and dynamic salivary flow rates (r=0.363, P=0.009). The patients with higher score of salivary gland ultrasonography (SGUS) had obviously lower cystatin D than those with lower SGUS score (parotid gland: 160.75±85.56 vs 290.53±95.17 pg/mL, P < 0.01; submandibular gland: 157.76±87.59 vs 276.25±97.06 pg/mL, P < 0.01). The cystatin D level was also negatively correlated with peripheral blood IL-6 level (r=-0.453, P=0.001) and CD4+ T cell count (r=-0.396, P=0.005) in the pSS patients. Conclusion Salivary cystatin D level can be used as an indicator of salivary gland damage for pSS patients.

Primary Sjögren syndrome (SS) is an autoimmune disease affecting exocrine glands, with predisposition to development of lymphoma (lymphomagenesis). We report a case of Sjogren’s syndrome and discuss the role of FDG PET/CT in the primary diagnosis of lymphoma transformation in SS. Furthermore, we reviewed the literature regarding the utility of FDG PET/CT to assess systemic disease activity and also its role in the SS associated lymphoma with light into the new PET tracers that can be explored for these indications in the future. Published data suggest promising role of FDG PET/CT in SS associated lymphomas, and demands larger studies for its establishment.

Purpose of Review: Sjögren Syndrome is a systemic autoimmune disorder that presents mainly with sicca symptoms, but frequently affects other body systems which can lead to a wide variety of manifestations. Understanding the neurological and psychiatric manifestations of Sjögren Syndrome can help with an earlier diagnosis of this disease and leads to better clinical outcomes. Recent Findings: We provide an updated overview of the central neurological manifestations, peripheral neurological manifestations and psychiatric manifestations and their diagnosis when associated with primary Sjögren Syndrome. The epidemiology and clinical features of the neurological and psychiatric manifestations are derived from different cohort studies and review articles that were selected from PubMed searches conducted between January 2024 and March 2024. Summary: The absence of diagnostic criteria and the scarcity of large, robust studies makes the recognition of the neurological and psychiatric manifestations of Sjögren Syndrome more difficult. Maintaining a high index of suspicion in clinical practice and a close collaboration between the Neurologist and the Rheumatologist will facilitate the diagnosis and management of these patients. [ABSTRACT FROM AUTHOR]

Abstract Background Primary Sjögren syndrome (pSS) is often related to adverse neonatal outcomes. But it’s currently controversial whether pSS has an adverse effect on female fertility and clinical pregnancy condition. More importantly, it’s unclear regarding the role of pSS in oocyte and embryonic development. There is a lack of comprehensive understanding and evaluation of fertility in pSS patients. Objective This study aimed to investigate oocyte and embryonic development, ovarian reserve, and clinical pregnancy outcomes in Primary Sjögren syndrome (pSS) patients during in vitro fertilization (IVF) treatment from multi-IVF centers. Methods We performed a muti-central retrospective cohort study overall evaluating the baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical pregnancy outcomes between the pSS patients and control patients who were matched by Propensity Score Matching. Results Following PSM matching, baseline characteristics generally coincided between the two groups. Ovarian reserve including anti-müllerian hormone (AMH) and antral follicle counting (AFC) were significantly lower in the pSS group vs comparison (0.8 vs. 2.9 ng/mL, P

Background: Primary Sjögren syndrome (pSS) is often related to adverse neonatal outcomes. But it's currently controversial whether pSS has an adverse effect on female fertility and clinical pregnancy condition. More importantly, it's unclear regarding the role of pSS in oocyte and embryonic development. There is a lack of comprehensive understanding and evaluation of fertility in pSS patients. Objective: This study aimed to investigate oocyte and embryonic development, ovarian reserve, and clinical pregnancy outcomes in Primary Sjögren syndrome (pSS) patients during in vitro fertilization (IVF) treatment from multi-IVF centers. Methods: We performed a muti-central retrospective cohort study overall evaluating the baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical pregnancy outcomes between the pSS patients and control patients who were matched by Propensity Score Matching. Results: Following PSM matching, baseline characteristics generally coincided between the two groups. Ovarian reserve including anti-müllerian hormone (AMH) and antral follicle counting (AFC) were significantly lower in the pSS group vs comparison (0.8 vs. 2.9 ng/mL, P < 0.001; 6.0 vs. 10.0, P < 0.001, respectively). The pSS group performed significant reductions in numbers of large follicles, oocytes retrieved and MII oocytes. Additionally, pSS patients exhibited obviously deteriorate rates of oocyte maturation, 2PN cleavage, D3 good-quality embryo, and blastocyst formation compared to comparison. As for clinical pregnancy, notable decrease was found in implantation rate (37.9% vs. 54.9%, P = 0.022). The cumulative live birth rate (CLBR) following every embryo-transfer procedure was distinctly lower in the pSS group, and the conservative and optimal CLBRs following every complete cycle procedure were also significantly reduced in the pSS group. Lastly, the gestational weeks of the newborns in pSS group were distinctly early vs comparison. Conclusion: Patients with pSS exhibit worse conditions in terms of female fertility and clinical pregnancy, notably accompanied with deteriorate oocyte and embryo development. Individualized fertility evaluation and early fertility guidance are essential for these special patients. [ABSTRACT FROM AUTHOR]

Primary Sjögren's Syndrome (pSS) is a systemic autoimmune disease that leads to reduced saliva production, primarily affecting women due to estrogen deficiency. The estrogen receptor α (ERα) plays a crucial role in mediating the expression of the aquaporin 5 (AQP5) gene through the estrogen response element-dependent signaling pathway, making ERα a key drug target for pSS. Several flavonoids have been reported to have the potential to treat pSS. This study aimed to screen and compare flavonoids binding to ERα using AutoDock, providing a basis for treating pSS with flavonoids. The estrogenic potential of six representative flavonoids was examined in this study. Molecular docking revealed that the binding energy of all six flavonoids to ERα was less than −5.6 kcal/mol. Apigenin, naringenin, and daidzein were the top three flavonoids with even lower binding energies of −7.8, −8.09, and −8.59 kcal/mol, respectively. Similar to the positive control estradiol, apigenin, naringenin, and daidzein showed hydrogen bond interactions with GLU353, GLY521, and HIS524 at the active site. The results of luciferase reporter assays demonstrated that apigenin, naringenin, and daidzein significantly enhanced the transcription of estrogen receptor element (ERE) in the PGL3/AQP5 promoter. Furthermore, molecular dynamics simulations using GROMACS for a time scale of 100 ns revealed relatively stable binding of apigenin-ERα, naringenin-ERα, and daidzein-ERα. Mechanistically, homology modeling indicated that GLU353, GLY521, and HIS524 were the key residues of ERα exerting an estrogenic effect. The therapeutic effect of apigenin on dry mouth in pSS models was further validated. In conclusion, these results indicate the estrogenic and pSS therapeutic potential of apigenin, naringenin, and daidzein.

Objectives Accurate distinguishing between immunoglobulin G4-related sialadenitis (IgG4-RS) and primary Sjögren syndrome (pSS) is crucial due to their different treatment approaches. This study aimed to construct and validate a nomogram based on the ultrasound (US) scoring system for the differentiation of IgG4-RS and pSS. Methods A total of 193 patients with a clinical diagnosis of IgG4-RS or pSS treated at our institution were enrolled in the training cohort (n  =   135; IgG4-RS = 28, pSS = 107) and the validation cohort (n  =   58; IgG4-RS = 15, pSS = 43). The least absolute shrinkage and selection operator regression algorithm was utilized to screen the most optimal clinical features and US scoring parameters. A model for the differential diagnosis of IgG4-RS or pSS was built using logistic regression and visualized as a nomogram. The performance levels of the nomogram model were evaluated and validated in both the training and validation cohorts. Results The nomogram incorporating clinical features and US scoring parameters showed better predictive value in differentiating IgG4-RS from pSS, with the area under the curves of 0.947 and 0.958 for the training cohort and the validation cohort, respectively. Decision curve analysis demonstrated that the nomogram was clinically useful. Conclusions A nomogram based on the US scoring system showed favourable predictive efficacy in differentiating IgG4-RS from pSS. It has the potential to aid in clinical decision-making. [ABSTRACT FROM AUTHOR]

Abstract Page: Background: Primary Sjogren's syndrome (pSS) is an autoimmune exocrinopathy in which extraglandular signs of pSS are determinant for the prognosis. Involvement of both peripheral and central nervous system (CNS) are known to be among the sites of high systemic activity in pSS. Case presentation: We, herein, report a case of a 57-year-old female patient with pSS presenting with typical Guillan-Barré syndrome (GBS), shortly followed by acute headaches accompanied by cortical blindness. Cerebral magnetic resonance imaging (MRI) demonstrated T2 signal abnormalities on the occipital region with narrowing and irregularities of the cerebral arteries, suggestive of CNS vasculitis.Subtle sicca symptoms occurring prior to neurological symptoms by 8 months together with immunological disturbances (anti-SSA, anti-SSB antibodies positivity, type II cryoglobulins positivity, and C4 hypocomplementemia) allowed us to retain the diagnosis of pSS. Recovery of motor symptoms was possible under the combined use of immunoglobulins and corticotherapy during the initial phase. A three-years follow-up confirmed progressive motor recovery and stabilization under 6-months cyclophosphamide cycles relayed by azathioprine therapy. Conclusions: Neurological complications can be inaugural in lead to urgent investigations and treatment. Peripheral and central neurological manifestations can coexist. The approach should integrate careful clinical assessment, as well as radiological and immunological findings.

Objective: To determine the prevalence, clinical features, risk factors, and prognosis of interstitial lung disease (ILD) in patients with primary Sjogren's syndrome (pSS). Methods: Data from 274 pSS patients from August 2013 to August 2022 were reviewed. The clinical features of pSS with ILD were revealed. Logistic regression was used to determine risk factors for ILD in pSS patients. Survival analysis and Cox regression were used to analyse the prognosis and prognostic factors of pSS patients. Results: In pSS patients, the prevalence of ILD was 22.3% (61/274). The pSS patients with ILD were characterized by a late onset and long disease course, with a nonspecific interstitial pneumonia (NSIP) pattern as the predominant high-resolution computed tomography (HRCT) finding. Logistic regression results indicated that an age over 50 years old (OR 4.786, 95% CI 1.602–14.299; P = 0.005), purpuric rash (OR 4.695, 95% CI 1.537–14.339; P = 0.007), AMA-M2 antibody positivity (OR 2.582, 95% CI 1.166–5.722; P = 0.019), and diabetes (OR 2.514, 95% CI 1.025–6.167; P = 0.044) were risk factors for ILD in pSS patients. Cox regression results showed that advanced age (HR 1.240, 95% CI 1.088–1.413; P = 0.001) and cancer history (HR 8.411, 95% CI 1.771–39.934; P = 0.007) were risk factors for pSS patient survival. Conclusion: This study showed that pSS patients with ILD tended to have a late onset and long course of pSS. An age over 50 years, purpuric rash, AMA-M2 antibody positivity, and diabetes were risk factors for ILD in pSS patients. Advanced age and cancer history were prognostic factors in pSS patients. Key Points • This study showed that pSS patients with ILD tended to have a late-onset and lengthy course of pSS, with the NSIP pattern as the predominant lung image. • The risk factors for ILD in pSS patients determined in this study were an age over 50 years, purpuric rash, AMA-M2 antibody positivity, and diabetes. • The prognostic risk factors for pSS patients were advanced age and cancer history. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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). Conclusion: 14-3-3η proteins are potential candidates for diagnostic marker, marker of disease activity, and predictor of lymphoma in PSS patients. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical characteristics and disease activity as well as their correlations with cytokine of patients with primary Sjogren syndrome ( pSS ) . Methods The clinical data of pSS patients hospitalized in our department were retrospectively analyzed. The patients were divided into different groups according to age, gender, pathology of labial gland and disease activity. The differences in clinical characteristics, cytokine and the relations between them were analyzed retrospectively. Results Totally, 91 cases were included in the study. Among them, the ratio between male and female was about 1 : 17.2 and 74.73% of the patients were elderly (5 50 years) and 25.27% were young and middle-aged (< 50 years). The labial gland biopsy revealed Chsholm grade I or above in 57.14% of patients. 93.41% of the patients developed extraglandular involvement. Lymphadenopathy was the most common (50.55%) in extraglandular manifestations, followed by pancytope-nia (45.05%) and elevated immunoglobulin (40.66% ). The main manifestations of the male pSS patients were arthritis/arthralgia, interstitial pneumonia disease, pancytopenia and elevated immunoglobulin. The young and middle-aged group had higher rates of fever and hypocomplementemia than the elderly group, while the latter had a higher rate of pancytopenia (especially granulocytopenia) than the young and middle-aged group (P < 0.01). The group with focal lymphocytic sialadenitis had higher rater of globulin elevation than the group without focal lympho-cytic sialadenitis. EULAR Sjogren's syndrome disease activity index (ESSDAI) and FS were negatively correlated with age. The increase rates of serum IL-2R, IL-8, TNFa in the group of moderate and high disease activity were significantly higher than those in the group with low disease activity. Conclusion The elderly pSS patients are more susceptible for pancytopenia, but their disease activity and extraglandular manifestations are less patent and serious, as compared to young and middle-aged patients. The patients with focal lymphocytic sialadenitis are more likely to be affected with salivary gland enlargement and elevated globulin. The increases of serum IL-2R, IL-8 and TNFa are more commonly seen in those patients with moderate and high disease activity. [ABSTRACT FROM AUTHOR]

Objective: We aimed to quantify the extent of salivary gland fibrosis using shear‐wave elastography (SWE) to assess its diagnostic value for primary Sjögren syndrome (pSS). Methods: A total of 58 pSS patients and 44 controls underwent SWE ultrasound evaluation of the parotid and submandibular glands. We measured the degree of salivary gland fibrosis in all participants and investigated the diagnostic accuracy of SWE for pSS and its relationship to disease progression. Results: The diagnostic sensitivity, specificity, and accuracy of pSS were highest when the critical Young's modulus values of the parotid and submandibular glands were 18.4 and 15.9 kPa, respectively, effectively improving the diagnostic value of pSS. The area under the SWE curve of the submandibular gland was higher than that of the parotid gland (z = 2.292, P = 0.02), suggesting that the submandibular gland was damaged earlier. The mean parotid gland thickness of pSS patients was thicker than in healthy controls (mean ± standard deviation 2.5 ± 0.3 vs 2.4 ± 0.2, P = 0.013]. SWE had a 70.3% sensitivity for diagnosing pSS patients with a disease duration of 5 years, but this did not differ significantly from pSS patients with a longer disease duration. Conclusions: SWE is a valid diagnostic method for pSS. The degree of salivary gland fibrosis related to secretory function and pathological progression, and quantitative measurements of tissue elasticity provide objective criteria for predicting damage in pSS. [ABSTRACT FROM AUTHOR]

Abstract Background and aims In this study, we aimed to compare the prevalence of restless legs syndrome (RLS) between primary Sjögren syndrome (PSS) patients and the healthy population and investigate the relationships between RLS and insomnia status, anxiety, depression, neuropathic pain, and lower extremity pain. Our case-control study, included 55 patients aged 18–65 who were diagnosed with PSS based on the 2016 ACR/EULAR criteria and 60 healthy controls aged 18–65. The pain levels of the participants were evaluated using the pain DETECT Questionnaire, the lower-extremity visual analog scale, and an algometer, all participants were screened for fibromyalgia syndrome, and their psychiatric parameters were evaluated with the Beck Depression Inventory and the Beck Anxiety Inventory. Insomnia status was assessed using the Insomnia Severity Index. The cases in the PSS group with and without restless legs syndrome were compared. Results While the rate of RLS in the PSS group was 26.7%, that in the control group was found as 9%, and the difference between the two groups was significant (p < 0.05). The severity of RLS in the PSS group was found to be significantly higher in comparison to that in the control group (p < 0.05). The PSS group had significantly higher lower-extremity pain, fibromyalgia, insomnia, depression, anxiety, and pain scores, as well as a significantly higher mean number of painful points, than the control group (p > 0.05). In the results of the multivariate regression analysis, depression and insomnia scores were identified as independent predictors for the presence of RLS in PSS cases (p < 0.05). Conclusions We found the prevalence and severity of restless legs syndrome higher in the primary Sjögren syndrome patients compared to the healthy participants in the control group. We identified depression and insomnia as independent predictors of the presence of restless legs syndrome in primary Sjögren syndrome cases.

Extraglandular manifestations (EGMs) in primary Sjogren's syndrome (pSS) represent the clinical expression of the systemic involvement in this disease. EGMs are characterized by a wide heterogeneity; virtually any organ or system can be affected, with various degrees of dysfunction. The existing gaps of knowledge in this complex domain of extraglandular extension in pSS need to be overcome in order to increase the diagnostic accuracy of EGMs in pSS. The timely identification of EGMs, as early as from subclinical stages, can be facilitated using highly specific biomarkers, thus preventing decompensated disease and severe complications. To date, there is no general consensus on the diagnostic criteria for the wide range of extraglandular involvement in pSS, which associates important underdiagnosing of EGMs, subsequent undertreatment and progression to severe organ dysfunction in these patients. This review article presents the most recent basic and clinical science research conducted to investigate pathogenic mechanisms leading to EGMs in pSS patients. In addition, it presents the current diagnostic and treatment recommendations and the trends for future therapeutic strategies based on personalized treatment, as well as the latest research in the field of diagnostic and prognostic biomarkers for extraglandular involvement in pSS. [ABSTRACT FROM AUTHOR]

Background: Primary Sjögren syndrome (pSS) is a multisystem disorder of autoimmune etiology, frequently involving peripheral nerves. Early detection of peripheral neuropathy (PN) manifestations might improve prognosis and disease control. The purpose of the study was to evaluate the predictive potential of hematological and immunological parameters associated with PN development in pSS patients. Methods: This single-center retrospective study included patients with pSS who were divided into two groups, according to the occurrence of neurological manifestations throughout the follow-up period. Results: From the total of 121 pSS patients included in the study, 31 (25.61%) developed neurological manifestations (PN+ group) during the follow-up period. At the moment of pSS diagnosis, 80.64% of PN+ patients exhibited increased disease activity, with ESSDAI scores above 14 (p = 0.001), and significantly higher values for VASp score (p = 0.001), with a mean value of 4.90 ± 2.45, compared to 1.27 ± 1.32 in the PN- group. The hematological assessment at the moment of pSS diagnosis revealed that neutrophils and neutrophil-to-lymphocyte ratio (NLR) were significantly higher in the PN+ group (p = 0.001), while lymphocytes, monocytes and monocyte-to-lymphocyte ratio (MLR) were significantly lower (p = 0.025, p = 0.13 and p = 0.003, respectively). Immuno-inflammatory parameters—gammaglobulins, complement fractions C3, C4, total proteins and vitamin D were significantly lower in the PN+ patients' group. In multivariate analysis, the independent predictive character for PN development in pSS patients was confirmed for NLR (95% CI 0.033 to 0.263, p = 0.012), MLR (95% CI −1.289 to −0.194, p = 0.008), gammaglobulins (95% CI −0.426 to −0.088, p < 0.003), complement fraction C4 (95% CI −0.018 to −0.001, p < 0.030) and vitamin D (95% CI −0.017 to −0.003, p < 0.009). Conclusions: Readily available and frequently used hematological and immunological markers, such as NLR, MLR, gammaglobulins, C4 and vitamin D could be helpful in predicting the neurological involvement in pSS patients. These biological parameters might become useful tools for clinicians to monitor disease progression and identify potentially severe extraglandular manifestations in pSS patients. [ABSTRACT FROM AUTHOR]

Purpose: 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). Materials and Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Primary Sjogren syndrome (pSS) is the second most common autoimmune disorder worldwide, which, in the worst scenario, progresses to Non-Hodgkin Lymphoma (NHL). Despite extensive studies, there is still a lack of knowledge about developing pSS for NHL. This study focused on cells' signaling in pSS progression to the NHL type of diffuse large B-cell lymphoma (DLBCL). Using bulk RNA and single cell analysis, we found five novel pathologic-independent clusters in DLBCL based on cells' signaling. B-cell receptor (BCR) signaling was identified as the only enriched signal in DLBCL and pSS peripheral naive B-cells or salivary gland-infiltrated cells. The evaluation of the genes in association with BCR has revealed that targeting CD79A, CD79B, and LAMTOR4 as the shared genes can provide novel biomarkers for pSS progression into lymphoma. [ABSTRACT FROM AUTHOR]

This study aimed to assess the d-dimer level in patients with primary Sjögren syndrome (pSS), uncover its relationship with clinical symptoms, and appraise its predictive value in discriminating disease activity. The laboratory parameters of 101 consecutive patients with pSS and 101 healthy controls were analyzed and compared. Patients were divided into two subgroups according to their d-dimer levels, for the comparison of clinical features. Pearson's correlations were used to measure the relationships between d-dimer levels and other variables. The area under the curve (AUC) was calculated to predict disease activity. The erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP) level, and d-dimer level were each higher in patients with pSS than in healthy controls. Compared with the low-d-dimer-level patients, those with elevated d-dimer levels exhibited higher ESRs (p < 0.0001) and higher levels of hsCRP (p < 0.0001), fibrinogen (p < 0.0001), and immunoglobulin A (p = 0.002). Cases with elevated d-dimer levels were prone to be more severe, based on ESSDAI evaluation (p < 0.0001). Patients with higher d-dimer levels had more articular involvement (p < 0.0001), which was significantly correlated with both the ESR (r = 0.21, p = 0.03) and hsCRP level (r = 0.56, p = 0.001). The d-dimer level may help to discriminate low disease activity from moderate/high disease activity (AUC = 0.754). The d-dimer level was correlated positively with both the ESR and hsCRP level in patients with pSS. The ESR and levels of hsCRP, fibrinogen, and disease activity were higher in the elevated d-dimer level group. The d-dimer level was demonstrated to have predictive value in differentiating pSS disease activity. Key Points •D-Dimer was higher in patients with pSS. •D-Dimer may help for predicting the disease activity in patients with pSS. [ABSTRACT FROM AUTHOR]

Background and aims: In this study, we aimed to compare the prevalence of restless legs syndrome (RLS) between primary Sjögren syndrome (PSS) patients and the healthy population and investigate the relationships between RLS and insomnia status, anxiety, depression, neuropathic pain, and lower extremity pain. Our case-control study, included 55 patients aged 18–65 who were diagnosed with PSS based on the 2016 ACR/EULAR criteria and 60 healthy controls aged 18–65. The pain levels of the participants were evaluated using the pain DETECT Questionnaire, the lower-extremity visual analog scale, and an algometer, all participants were screened for fibromyalgia syndrome, and their psychiatric parameters were evaluated with the Beck Depression Inventory and the Beck Anxiety Inventory. Insomnia status was assessed using the Insomnia Severity Index. The cases in the PSS group with and without restless legs syndrome were compared. Results: While the rate of RLS in the PSS group was 26.7%, that in the control group was found as 9%, and the difference between the two groups was significant (p < 0.05). The severity of RLS in the PSS group was found to be significantly higher in comparison to that in the control group (p < 0.05). The PSS group had significantly higher lower-extremity pain, fibromyalgia, insomnia, depression, anxiety, and pain scores, as well as a significantly higher mean number of painful points, than the control group (p > 0.05). In the results of the multivariate regression analysis, depression and insomnia scores were identified as independent predictors for the presence of RLS in PSS cases (p < 0.05). Conclusions: We found the prevalence and severity of restless legs syndrome higher in the primary Sjögren syndrome patients compared to the healthy participants in the control group. We identified depression and insomnia as independent predictors of the presence of restless legs syndrome in primary Sjögren syndrome cases. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the utility of magnetic resonance imaging (MRI) and magnetic resonance sialography (MRS) for diagnosis of primary Sjögren syndrome (pSS) singly or integrated with 2016 American College of Rheumatology (ACR)/European League Against Rheumatic Diseases (EULAR) classification criteria. Methods: The diagnostic efficiencies of MRI, MRS, and labial salivary gland biopsy (LSGB) were evaluated. The prediction model was established by multivariate analysis. Finally, performance of the ACR/EULAR criteria was evaluated after addition of MRI + MRS or replacement of original items by MRI + MRS. Results: The combined use of LSGB + MRI + MRS provided the greatest diagnostic value. MRI and MRS grade had positive correlations with disease duration and pathological grade of the labial gland (both P < 0.001). MRI and MRS grade had positive correlations with xerostomia severity and negative correlations with unstimulated salivary flow rate (both P < 0.001). The consistency of MRI grade and MRS grade in the diagnosis of parotid gland lesions was poor (κ = 0.253, P < 0.001). The diagnostic efficiency of our prediction model (AUC 0.906) was similar to that of criteria from the ACR/EULAR (AUC 0.930). Adding MRI + MRS to the ACR/EULAR criteria improved the sensitivity (92.3% vs 90.8%), whereas the specificity remained the same (88.9% vs 89.1%). Replacing LSGB by MRI + MRS in the ACR/EULAR criteria decreased both sensitivity and specificity (88.1% vs 90.8% and 86.4% vs 89.1%, respectively). Conclusion: The combined application of MRI and MRS has ideal clinical application value in the diagnosis of early‐stage pSS. Validity of the ACR/EULAR criteria remains high after incorporation of MRI + MRS. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate skeletal muscle architecture and strength in patients with primary Sjögren syndrome (pSS). Patients and methods: Between July 01, 2017 and November 30, 2017, 19 pSS patients (19 females; mean age: 54.1±6.6 years; range, 42 to 62 years) and 19 age-, body mass index-, and sex-matched healthy controls (19 females; mean age: 53.2±6.7 years; range 42 to 61 years) were included. Sjögren symptoms were assessed with the European Alliance of Associations for Rheumatology (EULAR) Sjögren’s Syndrome Patient Reported Index (ESSPRI). Muscle thickness, pennation angle, and fascicle length were measured at quadriceps femoralis, gastrocnemius and soleus muscles. Isokinetic muscle strength tests were performed at 60 and 180°/sec for knee and at 30 and 120°/sec for ankle. Anxiety and depression evaluated with the Hospital Anxiety and Depression Scale (HADS), fatigue with Multidimensional Assessment of Fatigue scale (MAF), and functionality with Health Assessment Questionnaire (HAQ). Results: In the pSS group, the mean ESSPRI was 7.70±1.17. The mean scores of depression (10.05±3.09 vs. 4.47±2.29; p<0.0001), anxiety (8.26±4.28 vs. 3.79±2.42; p<0.0001), functionality (0.94±0.78 vs. 0.22±0.26; p<0.0001), and fatigue (37.69±5.47 vs. 17.69±5.26; p<0.0001) were significantly higher in patients with pSS. Only, the pennation angle of vastus medialis in dominant leg was significantly greater in healthy controls (p=0.049). Peak torques/body weight of knee and ankle muscles were found to be similar. Conclusion: Excluding a minor decrease of the pennation angle at vastus medialis, muscle structure of lower extremity of pSS patients were similar to healthy controls. In addition, isokinetic muscle strength did not significantly differ in patients with pSS compared to healthy controls. In patients with pSS, disease activity and fatigue level were negatively correlated with isokinetic muscle strength measurements. [ABSTRACT FROM AUTHOR]

Primary Sjögren's syndrome is an autoimmune exocrinopathy related to lymphocytic infiltration of the exocrine glandular epithelia (such as salivary, lacrimal, nasal, and sebaceous glands or vaginal mucosa) with systemic manifestations of an immuno-inflammatory nature, and not associated with any other systemic disease. It is characterized by severe dryness (Sicca syndrome), particularly in mouth and eyes, with potential strong impact on quality of life and could increase the risk of depression in Sjögren's patient. To date, the impairment of taste and olfactory functions related to Sjögren syndrome remains poorly assessed; so is the trigeminal functions which remain sparsely studied in patients with Sjögren disease. However, other factors can also modify chemosensory functions (olfactory or gustatory sensations and trigeminal nerves), in particular the reduction of the masticatory coefficient or halitosis, due to oral saliva flow decrease, and poor dental condition, which are often present in Sjögren patients. Of the 12 articles evaluated after a 22-year literature search of this review, chemosensory disorders (including taste, smell, and trigeminal impairments) are described and evaluated in pSS patients, with mainly poorer performance compared to healthy controls. Diagnostic and therapeutic (including rehabilitation) approaches of chemosensory disorders in pSS are discussed in this review. Clinician should be more attentive to taste as well as olfacto-trigeminal disorders in primary Sjögren's disease, if possible at the earlier stage, in order to take the best care of Sjögren's patients. This review also highlights some lack in knowledge on pSS chemosensory disorders that should provide new research perspectives. Key Points •Chemosensory functions (including taste, smell, and trigeminal functions) are altered in patients with primary Sjögren's syndrome (pSS) due to dryness of the mouth and the nose. •The trigeminal nerve which interacts with olfactory and gustatory nerves contributes to olfactory and taste perception but remains little studied to date. •Chemosensory function should be considered in the daily clinical assessment of patients with pSS. •Chemosensory function treatment is not standardized yet, however symptomatic treatment of Sjögren syndrome-associated dryness transiently would improve taste and smell, and olfactory or gustatory rehabilitation in pSS patients would be useful. [ABSTRACT FROM AUTHOR]

Abstract Background Primary Sjögren syndrome (pSS) is a chronic autoimmune disease with its main target being exocrine glands, and is the connective tissue disease more frequently associated with other autoimmune diseases. The aim of this study was to assess the frequency of another autoimmune rheumatic disease (ARD) developed in primary Sjögren syndrome (pSS) patients and to describe it’s clinical, serological and histologic characteristics. Materials and methods This is a retrospective cohort study. Data of patients with pSS diagnosis (American-European criteria 2002), included in the GESSAR database (Grupo de Estudio Síndrome de Sjögren, Sociedad Argentina de Reumatología) were analyzed. The development of a second ARD was registered during the follow up. Results 681 patients were included, 94.8% female. The mean age was 54 (SD 14) years and mean age at diagnosis of 50 (SD 13) years. The mean follow-up was 4.7 (SD 4.9) years; 30 patients (4.41%, CI 95%: 3.1–5.7) developed a second ARD during the follow up, incidence rate was 9.1/1000 patients-year (IR 95%: 5.8–12.4/1000 patients-year), the most frequent being rheumatoid arthritis (RA). 96% out of these 30 patients had xerophthalmia, 86.2% xerostomia, 92% positive Schirmer test, 88.24% positive Rosa Bengala test, lisamine green or Ocular Staining Score, 81.2% positive unstimulated salivary flow, 82.1% Ro(+) and 33.33% La(+). Minor salivary gland biopsy had been performed in 14 of the 30 patients, 12 with positive results. There were no statistically significant differences respect baseline characteristics when comparing the patients who developed another ARD to the ones that did not. Conclusions Of all the patients analyzed, 4.4% presented another ARD during their follow-up. It is important to be aware of this, to make an early and proper diagnosis and treatment of our patients.

Primary Sjögren syndrome (pSjS) is one of the most prevalent systemic autoimmune diseases and characterized with hyperactivation of B cell and the abundant presence of autoantibodies in sera. The salivary gland epithelial cells (SGECs) release autoantigens to evoke autoimmunity through releasing elevated apoptosis or secreting autoantigen-containing exosomes, thus identifying autoantibodies directly to SGECs might provide insights into disease related biomarkers as well as further elucidating pathogenesis mechanisms. The present study was undertaken to identify autoantibodies to SGECs and to evaluate its clinical values in Chinese pSjS. Cell-based indirect immunofluorescence and immunostaining, two-dimensional electrophoresis and liquid chromatograph–tandem mass spectrometry were conducted to identify the autoantibodies to human salivary gland cell line A253 in pSjS sera. Enzyme-linked immunosorbent assay (ELISA) was applied to identify autoantibody titer in pSjS cohort and healthy controls. The prevalence and clinical significance of the identified autoantibodies was further assessed in pSjS population. Anti-calreticulin (CALR) antibody was identified as a new autoantibody directly to SGECs in sera from pSjS patients. Anti-CALR antibody were detected in 37 of 120 pSjS patients (30.83 %) and 1 of 54 healthy controls (1.85 %). It was found in 40.85 % pSjS with anti-SSA positive, 53.85 % with anti-SSB positive, and 14.7 % in sero-negative pSjS. Anti-CALR antibody was associated with clinical manifestations including weight loss(p = 0.045), vasculitis (p = 0.031), and laboratory parameters including erythrocyte sedimentation rate (ESR) (r = 0.056, p = 0.021), Krebs von den Lungen-6 (KL-6) (r = 0.121, p = 0.035), IgG (r = 0.097, p < 0.001), IgG2 (r = 0.142, p = 0.022), IgG3 (r = 0.287, p < 0.001), fibrinogen (r = 0.084, p = 0.016), D-Dimer (r = 0.086, p = 0.012) and fibrinogen degradation production (r = 0.150, p = 0.002). The expression of CALR in salivary glands was related to lymphocytes infiltration into salivary glands in pSjS patients (r = 0.7076, p = 0.0034). To our knowledge, this was the first study to investigate the prevalence and clinical significance of anti-CALR antibody in Chinses pSjS patients. The present study identified an autoimmune antibody, anti-CALR antibody, as a good autoimmune biomarker for sero-negative pSjS. [ABSTRACT FROM AUTHOR]

Abstract Background Interstitial lung disease (ILD) may cause life-threatening complications of primary Sjogren’s syndrome (pSS), and has a poor prognosis in terms of survival and quality of life. To date, few studies have investigated the risk factors for ILD detected by high-resolution computed tomography (HRCT) in pSS patients with or without respiratory symptoms. Methods Data of 333 patients with newly diagnosed pSS were retrospectively analysed. Interstitial lung disease involvement was defined as typical abnormalities on HRCT and/or pulmonary function tests. Multivariate regression model was used to evaluate the association between interstitial lung disease and pSS characteristics. Results Sixty-six patients (19.82%) were diagnosed with pSS-ILD. Ground glass opacities (87.88%) and septal/sub pleural lines (81.82%) were most frequent. Based on pulmonary high-resolution computed tomography, patients were divided into nonspecific (n = 42), usual (n = 20), lymphocytic interstitial pneumonia (n = 3) and cryptogenic organising pneumonia (n = 1) groups. There was a strong association between erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) and the HRCT-score. Pulmonary function tests revealed impaired diffusion capacity for carbon monoxide and total lung capacity, and coexistence of small airway lesions in pSS-interstitial lung disease. On logistic regression analysis, age, Raynaud’s phenomenon, lymphopenia, cough, dyspnoea and rampant dental caries were risk factors associated with pSS-interstitial lung disease. Conclusions Interstitial lung disease involvement in pSS is a common clinical occurrence. The clinical manifestation is nonspecific and variable; Raynaud’s phenomenon and lymphopenia may predict its onset. pSS patients with advanced age, dry cough and dyspnoea should be systematically evaluated for ILD involvement and managed according to their symptoms.

Aim: The aim of this study was to assess the prevalence of acute periapical lesions in patients with pSS. Methods: Integrated data of hospital patients was used. Data from the corresponding diagnosis codes for pSS and acute periapical abscess was retrieved by searching the appropriate query in the database. The patient population analyzed was mixed, presenting with different disease conditions including periapical abscesses without sinus. The different diagnoses were coded using the international coding systems ICD 10. Diagnosis was made by calibrated dentists in a hospital setting based on clinical examination and imaging data. Patients with ICD 10 diagnosis code of acute periapical abscess were recorded and the prevalence of acute periapical abscesses in patients with primary Sjögren syndrome were compared to the prevalence in the total hospital patient population. The odds ratio (OR) for the prevalence of acute periapical abscesses and its association with pSS were calculated with a 95% confidence interval and the statistical difference between the groups was assessed. Results: The odds ratio (OR) for the prevalence of acute apical abscesses and its association with pSS were calculated and analyzed statistically. The prevalence of periapical abscesses in patients with pSS was 1.87% as compared to 0.58% in the general patient population of the hospital. The OR was 3.11 and the difference was statistically significant (p

OBJECTIVE: To probe into the efficacy of rituximab in the treatment of recurrent primary Sjögren syndrome (pSS) associated dry eye, so as to provide reference for clinical treatment. METHODS: Totally 81 patients with recurrent pSS associated xerophthalmia admitted into this hospital from Jan. 2015 to Aug. 2021 were selected and divided into two groups by random number table. The control group (41 cases, 82 eyes) was given prednisone acetate, hydroxychloroquine sulfate and cyclophosphamide for systemic administration and topical eye drops for 8 weeks; while the observation group (40 cases, 80 eyes) were given rituximab 375 mg/m² for intravenous drip based on the control group, once a week for 8 weeks. Scores of the standard patient evaluation of eye dryness (SPEED) questionnaire, rupture time of tear film, scores of Schirmer Ⅰ tear secretion test and corneal fluorescein staining of the two groups were observed, incidence of adverse drug reactions and recurrence during follow-up were recorded. RESULTS: After treatment, the SPEED scores of eye dryness, foreign body sensation, pain, burning sensation or tearing and total score, and scores of corneal fluorescein staining of both groups were significantly lower than before treatment, the rupture time of tear film was longer than before treatment, and the length of Schirmer I tear secretionsoaked filter paper was increased compared with before treatment in both groups, with statistically significant differences (P<0. 01). The SPEED scores of eye dryness [(2. 15±0. 36) points vs. (3. 26±0. 47) points], foreign body sensation [(2. 11±0. 28) points vs. (3. 02±0. 40) points], pain [(2. 03±0. 28) points vs. (2. 95±0. 36) points], burning sensation or tearing [(1. 26±0. 24 ) points vs. (2. 15±0. 39) points] and total score [(7. 55± 1. 46) points vs. (11. 38±2. 74) points], and scores of corneal fluorescein staining [(3. 11±0. 53) points vs. (4. 02± 0. 69) points] of the observation group were lower than those of the control group after treatment, and the rupture time of tear film [(9. 57±2. 03) s vs. (7. 35±1. 95 ) s] of the observation group was longer than that of the control group, the length of Schirmer Ⅰ tear secretion-soaked filter paper [(8. 97 ±2. 17) mm vs. (6. 95 ±1. 72) mm] of the observation group was greater than that of the control group, with statistically significant differences (P<0. 01). The recurrence rate of the observation group [5. 00% (2/40) vs. 24. 39% (10/41)] was lower than that of the control group, with statistically significant difference (P<0. 05). The difference in the incidences of adverse drug reactions between two groups was not statistically significant ( P > 0. 05). CONCLUSIONS: Compared with conventional treatment, the application of rituximab for recurrent pSS associated dry eye can significantly induced lacrimal secretion, improved dry eye symptoms and reduced the risk of recurrence. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to assess the prevalence of acute periapical lesions in patients with pSS. Methods: Integrated data of hospital patients was used. Data from the corresponding diagnosis codes for pSS and acute periapical abscess was retrieved by searching the appropriate query in the database. The patient population analyzed was mixed, presenting with different disease conditions including periapical abscesses without sinus. The different diagnoses were coded using the international coding systems ICD 10. Diagnosis was made by calibrated dentists in a hospital setting based on clinical examination and imaging data. Patients with ICD 10 diagnosis code of acute periapical abscess were recorded and the prevalence of acute periapical abscesses in patients with primary Sjögren syndrome were compared to the prevalence in the total hospital patient population. The odds ratio (OR) for the prevalence of acute periapical abscesses and its association with pSS were calculated with a 95% confidence interval and the statistical difference between the groups was assessed. Results: The odds ratio (OR) for the prevalence of acute apical abscesses and its association with pSS were calculated and analyzed statistically. The prevalence of periapical abscesses in patients with pSS was 1.87% as compared to 0.58% in the general patient population of the hospital. The OR was 3.11 and the difference was statistically significant (p<0.0001). Conclusions: Under the conditions of this study, it appears that the prevalence of acute periapical abscesses is significantly higher in patients with pSS. [ABSTRACT FROM AUTHOR]

Purpose: To report the proportion of ocular involvement in primary Sjögren syndrome (pSS) and to analyze various dry eye indexes and serum titers of markers depending on whether ocular involvement has occurred or not., Methods: This retrospective study considered 214 patients referred from the rheumatology department for pSS workup. Symptom questionnaires, ocular surface stain score (OSS), Schirmer test, tear breakup time (TBUT), meibomian gland dropout, meibum quality, meibum expressibility, lid margin abnormalities, and lipid layer thickness were evaluated. Anti-Ro, anti-La, and antinuclear antibodies, rheumatoid factor, erythrocyte sedation rate, and C-reactive protein were included as systemic serum titers of markers. Patients with (group 1) and without (group 2) ocular involvement were compared. We conducted a further subgroup analysis of group 1 by dividing it into two groups based on whether or not the cases met all the ocular criteria for pSS diagnosis., Results: Among the 214 referred patients, 118 were diagnosed as pSS: 87 out of 118 (73.7%) in group 1 and 31 (26.3%) in group 2. Group 1 showed higher meibum quality scores (p = 0.016), meibum expressibility (p = 0.010), and lid margin abnormalities on the lower lid (p = 0.029) and lower TBUT (p = 0.016) than group 2. OSS, TBUT, and the Schirmer test statistically differed (p < 0.001, p = 0.041, and p = 0043, respectively) between the patients who satisfied both ocular criteria (n = 46) and those who satisfied only one criterion (n = 41). There were no statistical differences in serum titers of markers between the two groups., Conclusions: About half of patients referred from the rheumatology department for diagnosis of pSS were diagnosed with pSS. The proportion of ocular involvement in the pSS patients was 73.7%, and half of these patients met both ocular criteria. Only anti-Ro antibodies negatively correlated with TBUT. Also, OSS, TBUT, and Schirmer test were statistically different between the two subgroups.

BackgroundLung involvement in primary Sjögren’s syndrome (pSS) may vary from 9 to 90%. Interstitial lung disease and tracheobronchial alterations are the most typical findings. The evidence of primarily emphysematous changes at computed tomography of the chest of pSS patients has occasionally been described but poorly characterized. This study aims to assess pulmonary involvement and the impact on respiratory function in a cohort of pSS patients.Materials and methodsA total of 22 consecutive patients diagnosed with pSS underwent pulmonary function tests to investigate the presence of ventilatory impairment and evaluate the exchanges of alveolar gases. All patients underwent a chest high-resolution computed tomography (HRTC).ResultsDynamic volumes were within the normal range in 21 patients (95.4%). A reduction in the diffusing capacity of the lung for carbon monoxide (DLCO) was observed in 18 patients (81.8%). Ten (45.5%) patients showed a mild degree deficit, while 8 patients (36%) showed a moderate degree deficit. Analysis of DLCO revealed a significant difference between pSS patients and controls [t(30.98) = −10.77; p < 0.001], showing a higher DLCO value for the healthy controls (mean ± SE; 101.27 ± 6.08) compared to pSS patients (mean ± SE; 65.95 ± 12.78). Emphysema was found in 21 (94.5%) patients and was the most widespread pulmonary injury. Tracheal thickness was reduced in 15 (67%) patients. Micronodules were observed in 10 (45%) patients in all the pulmonary fields. Bronchial wall thickening and bronchiectasis were observed in 8 (36%) patients, mainly in the lower lobes. Ground glass was found in 5 (22.5%) patients in lower and higher lobes. Cysts were observed in two patients (9%).ConclusionThe reduction of the DLCO could be related to early emphysematous alterations in the absence of spirometric alterations and relevant respiratory symptoms. In conclusion, emphysema might be seen as an early pulmonary involvement mark in patients suffering from pSS.

Background: The pathomechanism of primary Sjögren syndrome (pSS) is multifactorial. Many cytokines take part in this process, including interferon. The study aimed to quantify certain cytokines involved in the pathomechanism of primary Sjögren syndrome (IL2, IL5, IL6, IL10, IL13, TNFα, IFNγ) and determine their common clinical correlation. On this basis, we discuss the potential use of anti-cytokine drugs in pSS therapy. Methods: The study group consisted of adult patients with a confirmed diagnosis of pSS. Results: The most frequently detected cytokines were IFNγ (82% of patients), TNFα (70%), IL6 (50%), and IL2 (42.5%). In all patients, except for one patient, IFNγ was found in the presence of other specific cytokines. There was no difference in clinical symptoms, age, and laboratory test results between the group of patients with IL-6 + TNFα + IFNγ positive cytokine, and the group of patients in whom they were not detected. There was no correlation between the presence of IL5, IL13, IL2, IL6, IL10, TNFα and musculoskeletal symptoms, skin lesions, glandular domains, pulmonary neurological, lymphadenopathy, biological and hematological domains in ESSDAI (p > 0.05). Conclusions: IFNγ most likely plays a central role in the pathomechanism of the disease. We have not noticed a clinical correlation between the three most common cytokines (IL6, IFNγ and TNFα), preliminary research results open up the possibility of searching for new treatments for pSS. The lower percentage of patients with detectable levels of TNFα and IL6 may explain the ineffectiveness of drugs targeting cytokines in clinical trials to date. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study is to evaluate the presence and frequency of central sensitisation (CS) in primary Sjögren Syndrome (pSS) and to determine the effect of CS on sleep quality. Materials and Methods: In this cross-sectional study, 50 patients diagnosed with pSS between the ages of 18 and 75 were included. The healthy control group was composed of 43 healthcare workers. Each participant underwent a physical examination, and demographic data and the medications they used were recorded. Central sensitisation inventory and Pittsburgh Sleep Quality Index questionnaires were filled in to garner data on CS and sleep quality, respectively, from all participants. Results: While central sensitisation inventory >40 was detected in 74% of pSS patients, it was 25.6% in healthy controls, and there is a statistically significant difference between the groups (p < .05). A correlation analysis of the central sensitisation inventory and Pittsburgh Sleep Quality Index values of all participants revealed a statistically significant correlation between all parameters other than the duration of sleep (p < .05). Conclusions: CS was found to have a negative effect on sleep quality in patients with pSS. We suggest that the cause of widespread pain seen in patients with pSS as the possible development of CS should be considered. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to assess the clinical characteristic of hypocomplementemia (HC) in primary Sjogren's syndrome (pSS), and to address possible risk factors and the prognosis associated with HC in pSS patients. Methods: pSS patients with HC in Hebei General Hospital from September 2016 to March 2019 were retrospectively analyzed and compared to those with normocomplementemia (NC). Logistic regression analysis was used to detect risk factors. Results: Of the 333 patients with pSS, 84 patients (25.23%) were presented with HC at diagnosis. The presence of hyper-IgG and anti-Ro52 antibodies was significantly more common in patients with HC. In addition to systemic involvement, pSS patients with HC had more hematological, renal, and nervous system involvement, and received more immunosuppressant treatments than NC group (p < 0.05). ESSDAI score was significantly higher in patients with HC (p < 0.05). Multivariate logistic analysis indicated that leukopenia (OR = 2.23) and hyper-IgG (OR = 2.13) were independent risk factors for pSS with HC. In addition, profound CD16/CD56+ NK-cell lymphopenia was found in pSS-HC patients. More pSS patients developed SLE in the HC group than NC group (4.76% vs. 0.80%, p = 0.04) during the follow-up. Conclusion: HC was not an uncommon manifestation of pSS and had an independent association with the main clinical and immunological features. Patients with pSS-HC had an increased possibility to develop SLE that required more positive treatment with glucocorticoids and immunosuppressants. Key Points: • Hypocomplementemia had an independent association with the main clinical and immunological features in primary Sjogren's syndrome patients. • ESSDAI score was significantly higher in patients with hypocomplementemia. • The pSS patients with hypocomplementemia had an increased possibility to develop SLE. [ABSTRACT FROM AUTHOR]

Objective: To study the clinical characteristics of patients with primary Sjögren syndrome(pSS) with purpura. Methods: A total of 101 patients with pSS were enrolled from January 2017 through January 2020 in Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. The patients were divided into 2 groups: pSS with purpura (purpura group, n=15) and without purpura (non-purpura group, n=86). The clinical presentations and laboratory data were compared between the 2 groups. Results: Of the 15 patients with manifestation of purpura (14.9%), 12(80%) were diagnosed as hypergammaglobulinemia purpura and the other 3(20%) were cryoglobulinemia purpura, thrombocytopenic purpura, and pigmented purpuric dermatosis, respectively. Four cases developed purpura prior to the glandular symptoms of dry mouth and eyes, and 11 cases had purpura after presentations of glandular symptoms. Com-paring with the non-purpura group, the pSS patients with purpura group had earlier onset age [(41.6±13.5) years vs. (51.7±11.4) years, P=0.003], higher incidence of lymphoma (2/15 vs. 0, P=0.011); higher serum levels of rheumatoid factor (RF) (P=0.002), erythrocyte sedimentation rate (ESR) (P=0.019), immunoglobulin (Ig) G (P

CD226 is an important receptor constitutively expressed on most immune cells, performing vital functions in immune responses. However, the levels of soluble CD226 (sCD226) and its roles in primary Sjögren syndrome (pSS) remain unclear. In this study, we developed two novel mouse anti-human CD226 monoclonal antibodies (mAbs) and established a novel sandwich enzyme-linked immunosorbent assay (ELISA) system, which proved to be highly effective in detecting human sCD226. We then analyzed the expression of sCD226 in the plasma of pSS patients. Our results showed that the levels of sCD226 were significantly lower in patients with pSS compared to healthy controls. The significant decline was also observed in active group and the patients with high levels of IgG or positive anti-SSB. Additionally, reduced sCD226 was found to be negatively correlated with the disease activity of pSS and several clinical manifestations, including arthralgia, fatigue, decayed tooth and interstitial lung disease (ILD). Furthermore, receiver operator characteristics (ROC) curve analysis showed that sCD226 displayed outstanding capacity in discriminating pSS and predicting the disease activity. Altogether, plasma sCD226 emerges as a promising candidate for diagnostic markers in the context of pSS. [Display omitted] • We successfully developed an innovative sandwich ELISA system for detection of human sCD226. • Reduced plasma sCD226 levels are associated with with disease activity in pSS. • Soluble CD226 emerges as a promising candidate for therapeutic targeting in the context of pSS. [ABSTRACT FROM AUTHOR]

• Continuous stimulation of autoreactive B cells by immune complexes is the first step towards the development of pSS. • Efficient regulation of hyperactivated B cells is crucial through the use of B cell receptor (BCR) targeting therapies to control clonal escape and the development of pSS. • pSS-specific B cells enhance the aggregation of BCRs at the B cell-APCs contact interface and trigger downstream signalling cascade events. Primary Sjögren's syndrome (pSS) is a systematic autoimmune manifestation of the exocrine glands caused by impaired lymphocytic infiltration, leading to dry eyes and xerostomia. The pathologic hallmark of this disease is the dysfunction of the exocrine glands, which results in dry eyes and mouth. Clinical observations suggest that B cells contribute to the pathogenesis of pSS through the enhanced secretion of autoantibodies, hypergammaglobulinemia, reduced free light chains, and a higher B cell lymphoma. Despite increased evidence of B cell hyperactivation and dysregulated B cell interactions in pSS, detailed speculations into the mechanism by which pSS-specific B cells exhibited abnormal BCR signaling repertoires and the magnitude of downstream signaling responses remain limited. Upon encountering antigens, B lymphocytes produce neutralizing antibodies by phosphorylating immune receptor tyrosine activation motifs (ITAMs). Despite these advancements, we still do not understand how pSS-specific B cells influence the surface clustering of BCRs and subsequent downstream immune responses. This paper hypothesizes that pSS-specific B cells encountering surrogate antigens will undergo a coordinated series of events that initiate B cell activation and spatiotemporal dynamics of BCRs. Additionally, we assume that pSS individuals have aberrant BCR repertoire and clonal expansion. In the future, these studies can provide detailed therapeutic entanglements for B cell-linked autoimmune and other hypersensitive disorders. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to compare initial albumin-to-globulin ratio (AGR) in patients with rheumatoid arthritis (RA) and primary Sjögren syndrome (pSS) presenting with undifferentiated arthritis (UA) and to investigate whether there was a difference in terms of AGR between the two patient groups and healthy controls. Patients and methods: Between January 2019 and December 2019, a total of 177 patients including 96 RA (10 males, 86 females; mean age: 53.6±10.8 years; range, 21 to 74 years) and 81 pSS (5 males, 76 females; mean age: 53.2±14.1 years; range, 23 to 79 years) and 82 healthy controls (20 males, 62 females; mean age: 50.5±13.6 years; range, 20 to 79 years) were included in this case-control study. Demographic characteristics, albumin, and globulin levels of all participants were recorded. The AGR, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-nuclear antibody (ANA), and anti-citrullinated protein antibodies (ACPA) were assessed. Results: The mean AGR was 1.50±0.16 in the control group, 1.48±0.24 in the RA group, and 1.30±0.23 in the pSS group, indicating a significant difference between the pSS and the other two groups (p<0.001). The receiver operating characteristic analysis revealed that the cut-off value for AGR was 1.39 (area under the curve=0.736) with a sensitivity of 0.642 and a specificity of 0.646 (p<0.001). The ESR and CRP values were higher (p<0.001), and ANA (p<0.001) and RF (p=0.003) positivity were lower in the RA group, compared to the pSS group. Conclusion: This study findings indicate that AGR is a helpful tool in the differential diagnosis of RA and pSS presenting with UA at the time of admission, and Sjögren syndrome should be considered in case of AGR ≤1.39. [ABSTRACT FROM AUTHOR]

Alors que diverses méthodes de classification ont été proposées pour déterminer l'épidémiologie du syndrome de Sjögren primitif (pSS), il est nécessaire de discerner si celui-ci est à considérer comme une maladie rare, c'est-à-dire, avec une prévalence inférieure à 50 cas pour 100 000 habitants. Parmi 11 analyses issues de 9 études basées sur des cohortes populationnelles, 8 concluent à une prévalence de moins de 50 cas pour 100 000 habitants et 2 méta-analyses confirment ces résultats, retrouvant de 39 à 43 cas pour 100 000 habitants. Il n'y a pas de différence notable entre les études où le diagnostic était posé par un médecin ou à l'aide des critères de classification AECG 2002. Aucune étude n'a utilisé jusqu'à présent les critères de classification ACR/EULAR 2016. Les femmes sont 6 à 9 fois plus touchées que les hommes, et présentent un pic d'incidence de la maladie entre 60 et 70 ans. Alors que les personnes d'origine Asiatiques sont les plus touchées, les Caucasiens sont également plus atteints par le pSS que les patients d'origine Africaine ou Hispaniques. En définitive, pouvoir considérer le syndrome de Sjögren primitif comme une maladie rare a des implications pour le clinicien, pour le développement de nouvelles molécules thérapeutiques et pour la mise en place des plans nationaux « maladies rares ». While several criteria for classification have been used for epidemiological studies about primary Sjögren syndrome (pSS), it remains unclear if pSS is an orphan disease. Among 11 analyses retrieved from 9 population-based studies, 8 show a prevalence lower than the orphan disease threshold (50/100,000 inhabitants). In two meta-analyses, prevalence is 39 to 43 per 100,000 inhabitants. There is no difference among prevalence in studies using or not classification criteria. ACR/EULAR 2016 criteria have not been used yet. Women are 6 to 9-fold more involved than men in pSS, and incidence for diagnosis is at the highest between 60 and 70 years old. Although Asian people are the most likely to present pSS, Whites are also more likely than Blacks or Hispanics. Collectively, pSS shall be now considered as an orphan disease, with important implications for clinicians, for development of new therapies and for national health programs. [ABSTRACT FROM AUTHOR]

Ultrasound (US) of major salivary glands (MSG) evaluates echogenicity, border features and vascularization, with elastography, it can detect tissue elasticity and glandular fibrosis, related to inflammation in Primary Sjögren’s syndrome (pSS). This study aimed to develop a novel technique by pixel analysis for evaluation and interpretation of elastography in MSG in pSS. A cross-sectional and observational multicenter study was conducted. The US of MSG performed in orthogonal planes in grayscale, Doppler, and shear-wave elastography. For elastography images of each gland were analyzed with the open-source program ImageJ to perform a pixel analysis. Statistical analysis was performed with the IBM-SPSS v25 program. Fifty-nine women with a mean age of 57.69 (23–83) years were recruited; pSS mean duration of 87 (5–275) months, and 12 healthy women without sicca symptoms as a control group with a mean age of 50.67 (42–60) years. Intragroup analysis showed p-values >0.05 between sicca symptoms, ocular/dryness tests, biopsy, US, and pixel analysis; correlation between Hocevar and pixel analysis was not found (rho < 0.1, p >0.5). MSG anatomical size was 41.7 ± 28.2 mm vs. 67.6 ± 8.8 mm (p ≤ 0.0001); unstimulated whole saliva flow rate was 0.80 ± 0.80 ml/5 min vs. 1.85 ± 1.27 ml/5 min (p = 0.016). The elastography values (absolute number of pixels) were 572.38 ± 99.21 vs. 539.69 ± 93.12 (p = 0.290). A cut-off point risk for pSS identified with less than 54% of red pixels in the global MSG mass [OR of 3.8 95% CI (1.01–15.00)]. Pixel analysis is a new tool that could lead to a better understanding of the MSG chronic inflammatory process in pSS.

Objectives: This study aims to evaluate serum lipoprotein-associated phospholipase A2 (Lp-PLA2) level and carotid intima-media thickness in primary Sjögren syndrome (pSS) as an indicator of atherosclerosis. Patients and methods: Between July 2019 and July 2020, a total of 33 female pSS patients (mean age: 44.5±11.2 years; range, 23 to 60 years) and 37 female age- and sex-matched healthy individuals (mean age: 40.9±7.2 years; range, 25 to 54 years) were included. Carotid intima-media thickness and serum Lp-PLA2 levels were measured in the patient and control groups. Results: The patients had a higher median serum Lp-PLA2 of 560 (range, 108 to 1,222) ng/mL vs. 328 (range, 0 to 1,280) ng/mL in the controls (p=0.024) and a similar mean intima-media thickness of carotid artery (0.64±0.14 mm vs. 0.62±0.15 mm, respectively; p=0.595). Serum Lp-PLA2 was positively correlated with platelet count (r=0.411, p=0.018) and negatively correlated with erythrocyte sedimentation rate (r=-0.409, p=0.018). The mean value of carotid intima-media thickness was positively correlated with disease duration (r=0.316, p=0.074) and was negatively correlated with the level of leucocyte (r=-0.458, p=0.007). Conclusion: Our study suggests that the patients of pSS have a potential risk of atherosclerotic cardiovascular disease, independent of traditional cardiovascular risk factors and disease severity. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung disease (ILD) may cause life-threatening complications of primary Sjogren's syndrome (pSS), and has a poor prognosis in terms of survival and quality of life. To date, few studies have investigated the risk factors for ILD detected by high-resolution computed tomography (HRCT) in pSS patients with or without respiratory symptoms.Methods: Data of 333 patients with newly diagnosed pSS were retrospectively analysed. Interstitial lung disease involvement was defined as typical abnormalities on HRCT and/or pulmonary function tests. Multivariate regression model was used to evaluate the association between interstitial lung disease and pSS characteristics.Results: Sixty-six patients (19.82%) were diagnosed with pSS-ILD. Ground glass opacities (87.88%) and septal/sub pleural lines (81.82%) were most frequent. Based on pulmonary high-resolution computed tomography, patients were divided into nonspecific (n = 42), usual (n = 20), lymphocytic interstitial pneumonia (n = 3) and cryptogenic organising pneumonia (n = 1) groups. There was a strong association between erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) and the HRCT-score. Pulmonary function tests revealed impaired diffusion capacity for carbon monoxide and total lung capacity, and coexistence of small airway lesions in pSS-interstitial lung disease. On logistic regression analysis, age, Raynaud's phenomenon, lymphopenia, cough, dyspnoea and rampant dental caries were risk factors associated with pSS-interstitial lung disease.Conclusions: Interstitial lung disease involvement in pSS is a common clinical occurrence. The clinical manifestation is nonspecific and variable; Raynaud's phenomenon and lymphopenia may predict its onset. pSS patients with advanced age, dry cough and dyspnoea should be systematically evaluated for ILD involvement and managed according to their symptoms. [ABSTRACT FROM AUTHOR]

Objective: This work aims to evaluate the long-term safety of rituximab (RTX) in primary Sjögren syndrome (pSS) and to determine the safety and the efficacy of long-term treatment with B cell depleting therapy in pSS patients with active systemic disease.Methods: A historical cohort study, enrolling 35 patients with pSS treated with RTX between 2008 and 2019 in a single rheumatologic unit, was performed. When patients experienced adverse events, the treatment was suspended and patients' data were recorded.Results: The included patients were mainly female (91%), with a mean age of 54 years. During the time of observation, 13 patients (37.1%) suspended RTX treatment (10 cases per 100 patient-years, 95% CI 0.06-0.17). Baseline demographics, disease characteristics, European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) values, and treatment were comparable across RTX-suspended and nonsuspended groups. Patients exposed to RTX had been followed for 35.82 ± 32.56 months, and the time of observation varied from 6 to 96 months. All the patients except one experienced a significant and persisting meaningful improvement of their ESSDAI (≥ 3 points) during the long-term follow-up. For the duration of the follow-up, 13 (37%) patients discontinued RTX treatment. Four out of 13 (30.8%) discontinued the treatment after the first administration due to infusion-related reactions. During subsequent RTX courses, the main cause of withdrawal was hypogammaglobulinemia onset (7 patients). In 2 patients, hypogammaglobulinemia was associated with severe infections.Conclusion: Long-term RTX administration was shown to be a safe, well tolerated, and effective treatment in patients with active systemic disease, significantly reducing ESSDAI and controlling disease activity. [ABSTRACT FROM AUTHOR]

Primary Sjögren’s syndrome (pSS) includes a rarer subtype with positive anti-centromere antibodies, which appears to be linked with scleroderma features and at higher risk of developing lymphoma. Two female patients were evaluated in our department for severe dryness of the mouth and eyes. The younger history of recurrent corneal ulcers. They both described Raynaud’s phenomenon and either had sclerodactily or facial teleangiectasias. The patients shared lymphopenia, negative anti-Ro and anti-La antibodies, positive high titer anti-centromere antibodies (ACA). The capillaroscopy exam revealed a scleroderma-like pattern. Minor gland biopsy reported a massive inflammatory lymphoplasmacytic infiltrate. One of the patients developed pulmonary lymphoma. The ACA positive pSS is associated with more severe sicca symptoms but can also fulfill criteria for systemic sclerosis. More research is necessary to link this subtype to the risk of developing hematological malignancies.

• IFN-α is a key pathogenic player in multiple autoimmune rheumatic diseases. • Anti IFN-α drugs may benefit to lupus, Sjögren, systemic sclerosis and dermatomyositis patients. • Several anti IFN-α treatments are currently evaluated in clinical and preclinical studies. • Patients will most likely benefit from anti IFN-α therapies within a precision medicine approach. Interferon (IFN)-α has emerged as a major therapeutic target for several autoimmune rheumatic diseases. In this review, we focus on clinical and preclinical advances in anti-IFN-α treatments in systemic lupus erythematosus (SLE), primary Sjögren syndrome (pSS), systemic sclerosis (SSc), and dermatomyositis (DM), for which a high medical need persists. Promising achievements were obtained following direct IFN-α neutralization, targeting its production through the cytosolic nucleic acid sensor pathways or by blocking its downstream effects through the type I IFN receptor. We further focus on molecular profiling and data integration approaches as crucial steps to select patients most likely to benefit from anti-IFN-α therapies within a precision medicine approach. [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence of axial articular manifestations (AAMs) in patients with primary Sjögren syndrome (pSS), to investigate whether these symptoms reveal an associated spondyloarthritis (SpA), and to assess their therapeutic management.Methods: Among 148 consecutive patients with pSS fulfilling European League Against Rheumatism (EULAR)/American College of Rheumatology 2019 classification criteria followed between 2010 and 2018, we selected those who presented with AAMs. The association with SpA was retained when patients fulfilled Assessment of SpA international Society criteria.Results: A total of 29 patients (20%, 28 women) with a median age of 43 years (range 15-65 yrs), were identified. The main extraglandular features were peripheral arthralgia and arthritis in 93% and 90% of patients, respectively. Positive anti-Ro/SSA (anti-SSA) antibody was reported in 62%. AAMs were inaugural in 7%, delayed from the diagnostic of pSS in 7%, and occurred concomitantly in 86% of patients. AAMs were not associated to multisystemic involvement of pSS. Radiographic sacroiliitis was mentioned in 65%, and HLA-B27 was positive in 13%. The diagnosis of SpA was retained in 23/29 patients (79%), among which 74% and 26% fulfilled psoriatic arthritis and ankylosing spondylitis criteria, respectively. There was no phenotypic difference according to the anti-SSA antibody status. With a median follow-up of 60 months (range: 5-96), 61% of patients with associated SpA required biotherapies, mainly of anti-tumor necrosis factor-α or anti-interleukin 17A molecules with a good clinical outcome in 64% and no effect on pSS.Conclusion: AAMs are not uncommon in patients with pSS and may reveal an associated SpA. Treatment of AAMs, especially when clearly associated with SpA, may necessitate biologics, following SpA-management therapeutic guidelines. [ABSTRACT FROM AUTHOR]

Abstract Objective Primary Sjögren syndrome (pSS) is characterized by T and B cell infiltration of exocrine glands. The cysteine protease cathepsin S (CatS) is crucially involved in MHCII processing and T cell stimulation, and elevated levels have been found in patients with RA, psoriasis and pSS. However, little is known about the functional characteristics and mechanisms of SS-A- and SS-B-specific T cells in pSS patients. We herein investigated the inhibition of CatS activity in different biocompartments of pSS patients including antigen-specific T cell responses. Methods Ex vivo CatS activity was assessed in tears, plasma and saliva of 15 pSS patients and 13 healthy controls (HC) and in the presence or absence of the specific CatS inhibitor RO5459072. In addition, antigen (SS-A (60kD), SS-B, influenza H3N2, tetanus toxoid and SEB)-specific T cell responses were examined using ex vivo IFN-γ/IL-17 Dual ELISPOT and Bromdesoxyuridin (BrdU) proliferation assays in the presence or absence of RO5459072. Supernatants were analysed for IL-1β, IL-6, IL-10, TNF-α, IL-21, IL-22 and IL-23, using conventional ELISA. Results CatS activity was significantly elevated in tear fluid, but not other biocompartments, was inversely associated with exocrinic function in pSS patients and could significantly be suppressed by RO5459072. Moreover, CatS inhibition by RO5459072 led to strong and dose-dependent suppression of SS-A/SS-B-specific T cell effector functions and cytokine secretion by CD14+ monocytes. However, RO5459072 was incapable of suppressing SS-A/SS-B-induced secretion of cytokines in CD14+ monocytes when T cells were absent, confirming a CatS/MHCII-mediated mechanism of suppression. Conclusion CatS activity in tear fluid seems to be a relevant biomarker for pSS disease activity. Conversely, CatS inhibition diminishes T cell and associated monokine responses towards relevant autoantigens in pSS. Thus, CatS inhibition may represent a promising novel treatment strategy in pSS.