Sjögren's Syndrome Group Research Articles

Oral Mucosal Human Papillomavirus and Epstein-Bar Virus Rates in Patients with Dry Mouth and/or Sjögren's Syndrome in a Hungarian Cohort.

To find an association between oral mucosal human papilloma- and/or Epstein-Barr (HPV, EBV) virus infection in patients with dry mouth and/or Sjögren's syndrome (SS) compared to healthy controls and to find connections with salivary gland histopathological alterations. Ninety-two participants were divided into four groups: 1. healthy controls (n = 32); 2. xerostomia (n = 28); 3. hyposalivation (n = 22); and 4. SS groups (n = 10). To detect virus infection brush biopsy was outlined in all groups. Detections of virus-specific sequences were achieved with polymerase chain reaction (PCR). Lip biopsy and histopathological assessment was performed in groups 2, 3 and 4. HPV positivity of oral mucosal cells was shown in group 1: 1 (3.12%); group 2: 3 (10.7%); group 3: 2 (8.26%); and in group 4: 0 of the samples. EBV was present in group 1: 14 (43.7%); group 2: 17 (60.7%); group 3: 6 (27.3%); and in group 4: 5 (50%) of the cases. There was no statistically significant difference between the attributes. Intact salivary gland in 28.2%, chronic sialadenitis in 28.2%, stromal fibrosis in 6.5%, lipomatous atrophy in 8.6%, fibrous atrophy in 6.5% and positive focus score (SS) in 26.1% were found in the subjects. Neither HPV nor EBV infection caused statistically significantly more histological abnormalities. Orofacial mucosal HPV and/or EBV DNA rates did not differ statistically significantly in patients with xerostomia or hyposalivation or SS compared to healthy controls, therefore, it cannot prove the provocative role of these viruses in dry mouth and/or SS. Neither dry mouth nor SS were accompanied by statistically significantly more salivary gland alterations in HPV- and/or EBV-positive subjects; these alterations are frequent in the virus-negative cases too.

Subjective Symptoms and Disease Activity Related to Serum Zinc Concentration in Primary Sjögren's Syndrome.

Background/Objectives: We examined the frequency of zinc deficiency in patients with Sjögren's syndrome (SS) and the relationship between zinc deficiency and each of the subjective symptoms and disease activity. Methods: We enrolled 164 patients aged ≥ 20 years with primary SS (pSS) based on the revised diagnostic criteria of the Ministry of Health, Labor and Welfare (1999) and 144 patients with RA diagnosed according to the ACR/EULAR classification criteria for RA (2010) as a comparison group. Subjective symptoms were confirmed using an original questionnaire, and disease activity was determined using the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI). The serum zinc concentrations were measured in both SS and RA patients. Results: The rate of zinc deficiency in the SS group was 26.1%, significantly higher than that in the RA group (7.6%). The rate of zinc deficiency was significantly higher in the pSS group compared with Japanese health checkup recipients reported in the literature. The mean serum zinc concentration in primary SS was 60.6 ± 7.3 µmol/L in the high disease activity group with an ESSDAI of ≥5 points, which was significantly lower than the concentration of 69.7 ± 10.2 µmol/L in patients with an ESSDAI of ≤4 points. Conclusions: The frequency of zinc deficiency was higher in patients with pSS than in patients with RA. Disease activity was also higher in patients with zinc deficiency, suggesting an association between zinc concentration and organ involvement in pSS.

Clinical characteristics and labial gland pathological features in children with systemic lupus erythematosus complicated by Sjögren's syndrome

To study the clinical manifestations, laboratory features, and labial gland pathological features in children with systemic lupus erythematosus (SLE) complicated by Sjögren's syndrome (SS). A retrospective analysis was conducted on 102 children with SLE who underwent labial gland biopsies at Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2022. The children were divided into two groups based on the presence of SS: the SLE with SS group (SLE-SS; 60 children) and the SLE-only group (42 children). According to the focus score (FS) of the labial glands, children in the SLE-SS group were further subdivided into FS≥4 subgroup (26 children) and FS<4 subgroup (34 children). The clinical data of the groups were compared. Compared to the SLE-only group, children in the SLE-SS group had less skin and mucosal involvement, were more likely to have positive anti-SSA and anti-SSB antibodies, and had higher levels of rheumatoid factor (P<0.05). There was no significant difference in treatment protocols between the two groups (P>0.05). Compared to the FS<4 subgroup, the FS≥4 subgroup had more frequent musculoskeletal involvement (P<0.05), but there was no significant difference in SLE disease activity or other major organ involvement between the subgroups (P>0.05). Children with SLE complicated by SS are less likely to have skin and mucous membrane involvement and exhibit specific serological characteristics. The SLE-SS children with an FS≥4 are more likely to experience musculoskeletal involvement. However, FS is not associated with disease activity or other significant organ damage.

Does stress response axis activation differ between patients with autoimmune disease and healthy people?

Many studies have shown that patients with autoimmune disease present a hypoactive hypothalamic-pituitary-adrenal (HPA) axis, but the results are controversial. Our objective was to study differences in stress response axis activity between patients with autoimmune disease and healthy people. The study sample consisted of 97 women divided into four groups: 37 healthy women (HW), 21 with systemic lupus erythematosus (SLE), 21 with Sjögren's syndrome (SS), and 18 with systemic sclerosis (SSc). After being exposed to a stress task, participants' skin conductance and salivary cortisol levels were measured in order to assess their response to psychological stress. Diurnal cortisol concentrations were assessed by measuring salivary cortisol in samples collected five times over one day. In addition, self-administered questionnaires were used to assess psychological variables. A time×group interaction effect was found (p=0.003) in salivary cortisol secretion in response to stressful challenge. The healthy group presented normal activation, the SS and SLE groups showed no activation, and the SSc group presented a similar activation pattern to the HW group, except at the time of recovery. Total cortisol production (AUCg) was higher in the SSc group than in the HW group (p=0.001). Differences were also observed in the cortisol AUCg collected over one day between healthy women and patients with SLE (p=0.004) as well as with SSc (p=0.001): women with SLE and SSc presented higher total hormone production than healthy women. Patients with autoimmune disease present a different HPA axis response, which may contribute to the harmful effects of stress in these diseases.

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.

Textural Analysis of Magnetic Resonance Images as an Additional Evaluation Tool of Parotid Glands in Sjögren-Primarily Findings.

Magnetic Resonance Imaging (MRI) plays a leading role in diagnosing soft tissue pathologies, especially in the head and neck. It is increasingly popular for evaluating salivary gland issues like neoplasms and Sjogren's Syndrome. Advanced MRI methods, including MRI sialography and texture analysis, offer non-invasive alternatives, enhancing MRI's role. This study focused on the relationship between the apparent diffusion coefficient (ADC) and T2-weighted MRI sialography and texture analysis (TA) of parotid glands in children with and without Sjogren's Syndrome (SS). Using 3.0 Tesla MRI with DWI and T2-weighted imaging, expended texture analysis, first-order statistics (FSOs), second-order, and higher-order statistics were conducted. The results showed significant differences in parotid ADC values, with lower values in the SS group, particularly in cases of higher disease activity. Lower kurtosis values were associated with more severe Tonami Scale grades. FSO parameters correlated well with the texture analysis from T2-weighted images, indicating promise in grading parotid gland inflammation. However, further research is needed to understand the impact of variables like binning and region of interest (ROI) size. This study highlights the potential of texture analysis for assessing parotid gland inflammation and emphasizes the need for more investigations in this area.

Three Signs to Help Detect Sjögren's Syndrome: Incidental Findings on Magnetic Resonance Imaging and Computed Tomography.

This study aimed to retrospectively investigate the prevalence of Sjögren's syndrome (SS) among patients with ranulas, parotid cysts, or parotid calcifications; identify the characteristic magnetic resonance imaging (MRI) or computed tomography (CT) findings of the lesions associated with SS; and compare the SS disease stages among SS patients with the three lesion types. A total of 228 patients with the lesions were classified into SS, possible SS, and non-SS groups. The prevalence of SS among patients with ranulas, parotid cysts, or parotid calcifications was 16%, 24%, and 40%, and the rates of either SS or possible SS were 25%, 41%, and 64%, respectively. SS was associated with (i) ranulas: ≤17 mm; (ii) parotid cysts: bilateral and multiple; and (iii) parotid calcifications: in females, bilateral, multiple, parenchymal, and no coexisting calcifications in other tissues. SS patients with ranulas were significantly younger and had lower submandibular gland stage scores on MRI/CT than those with other lesions. Additionally, in 58% and 15% of SS patients with ranulas and parotid calcifications, respectively, detection of the lesions led to the diagnosis of primary SS. Therefore, recognizing the prevalence of SS among patients with these lesions and the findings associated with SS can help detect undiagnosed SS.

Hyposalivation but not Sjögren's syndrome associated with microbial dysbiosis in women.

Saliva modulates the environment of the oral biofilm through pH buffer, microbial attachment to host surfaces, and nutritional source. The ecology of stress occurs when a physical factor adversely impacts an ecosystem or its biotic components. Therefore, reduced salivary flow can affect oral-host balance. The leading causes of hyposalivation include disease-associated Sjögren's syndrome (SS) and menopausal women as aging-associated. However, little is known about the oral microbiome integrated with sex hormones in hyposalivation. This study aimed to characterize the hyposalivation microbiome caused by aging or disease affecting the salivary glands in women. We included 50 women older than 40 years of age in any menopausal phase. We collected stimulated saliva from 25 women diagnosed with SS (SS) and 25 without SS (non-SS). The bacterial profile of the patients was obtained by 16S rRNA sequencing. Bioinformatics analysis used machine learning to analyze the cohort's signs, symptoms, and bacterial profile. Salivary estradiol as a sex hormone variation level was determined. We obtained that 79% of the SS group, and 52% of the non-SS group had hyposalivation. We found a negatively correlated Prevotella-age and Rothia-estradiol in the SS group. Highlight, we found that the cause of the hyposalivation in the study did not explain differences in microbial diversity comparing non-SS and SS groups. Therefore, microbial communities found in hyposalivation but not related to systemic conditions suggest that changes in the oral environment might underpin host-microbial balance. The salivary microbiome was similar in women with and without SS. However, hyposalivation showed two distinctive clusters associated with the bacterial population profiles. Our study suggests that local ecological disturbances could drive the change in the microbiome.

Predictors for future development of systemic lupus erythematosus in Korean Sjögren's syndrome patients.

This study determined the impact of demographic factors, clinical manifestations, disease activity, and serological tests at baseline on future SLE development in Sjögren's syndrome (SS) patients. This retrospective study assessed 1,082 SS patients without other autoimmune diseases at baseline who visited our hospital between January 2012 and March 2021. We analyzed demographic features, extra-glandular manifestations (EGMs), clinical indices, and laboratory values at baseline between the two groups divided per future SLE development (SS/SLE group vs SS group). The probability and predictors of SLE development in SS patients were estimated using the Kaplan-Meier method and Cox proportional hazards models. The median follow-up duration was 1083.5days. Forty-nine patients (4.5%) developed SLE that met the 2012 Systemic Lupus International Collaborating Clinics or 2019 EULAR/ACR classification criteria. The baseline EULAR SS disease activity index (ESSDAI) score was significantly higher in the SS/SLE group (p < .001). The SS/SLE group had more lymphadenopathy and renal involvement (p = .015 and p = .017, respectively). Shorter SS disease duration (<3years) (hazard ratio [HR] = 2.12, p = .0328), high ESSDAI (HR = 8.24, p < .0001), leukopenia (HR = 4.17, p = .0005), thrombocytopenia (HR = 3.38, p = .0059), hypocomplementemia (HR = 29.06, p<.0001), and positive for anti-dsDNA (HR = 13.70, p < .0001), anti-ribonucleoprotein (RNP) (HR = 3.82, p = .0027), and anti-ribosomal P (HR = 6.70, p = .0002) at baseline were SLE development predictors in SS patients. Shorter disease duration and higher disease activity of SS at baseline may be risk factors for future SLE development. Serologic predictors of SLE development are hypocomplementemia, leukopenia, thrombocytopenia, and positivity for anti-dsDNA, anti-RNP, and anti-ribosomal P antibodies. If the above factors are observed, close monitoring will be necessary during the follow-up period, considering the possibility of future SLE development.

Impairment of oral health and its impact on the quality of life of patients with Sjögren's syndrome

AbstractObjectivesThis study aimed to describe the clinical profile and the oral health status and their impact on the quality of life of patients with Sjögren's syndrome (SS).MethodsThrough a cross‐sectional study, patients with SS were compared with those with dry symptoms with no conclusive diagnosis of SS (non‐SS) and patients without complaints of dryness, matched for sex and age (control group). Data related to classification of SS, focus score, unstimulated whole salivary flow (UWSF), dental plaque index, periodontal screening and recording (PSR), decayed, missing and filled teeth (DMFT), and clinical signs of candidiasis were assessed. Colony‐forming units (CFU) of Candida spp were assessed and saliva biochemical analysis was also performed. The Xerostomia Inventory (XI) and Oral Health Impact Profile 14 (OHIP‐14) questionnaire were applied to assess the severity of xerostomia and quality of life.ResultsThirty‐three patients with primary SS, 22 with secondary SS, nine non‐SS, and 23 from control group were included. Patients with primary SS, secondary SS and non‐SS had lower UWSF and higher rates of plaque, PSR and DMFT than the control group. Candida spp. count was also higher in SS groups. Osmolality, buffering capacity and protein concentration in saliva were similar between groups. The scores of XI and OHIP‐14 were higher in the SS and non‐SS groups and showed positive correlation with PSR and DMFT and negative correlation with UWSF.ConclusionSS is associated with poor oral health, mainly related to dental and periodontal problems, which exert a negative impact on quality of life.

Clinical Features of Sjögren Syndrome-Related Dry Eye Disease in Anterior Segment Photographs.

Dry eye disease (DED) is a major complication of autoimmune disorders, including Sjögren syndrome (SS), ocular graft-versus-host disease, and other rheumatic diseases. DED often affects patients' quality of life, necessitating early detection and treatment. However, no simple screening method for DED has yet been established in ophthalmologic practice. This retrospective study aimed to identify the characteristic features of SS-related DED from anterior segment images. Five hundred two cases (SS, 68 cases; ocular graft-versus-host disease, 50 cases; other conditions, 27 cases; simple DED, 72 cases; and no DED, 97 cases) were enrolled. The inferior corneal fluorescein staining score (CFS_I) was significantly higher in the SS group ( P < 0.001). Moreover, the nasal lissamine green staining score (LG_N) was high in the SS group ( P < 0.001). The sensitivity, specificity, and area under the curve of the receiver operating characteristic curve were calculated for the CFS_I plus LG_N in relation to the SS-positive and SS-negative statuses; the sensitivity and specificity were 80.6% and 91.1%, respectively, with an area under the curve of 0.926. A positive CFS_I combined with a positive LG_N correlates with a high risk for SS. A positive CFS_I and a positive LG_N are important signs for an immune-related DED, especially SS, and may be useful in the early detection of SS-related DED.

Evaluation of fetal thymus size in maternal autoimmune diseases: systemic lupus erythematosus, Sjögren's syndrome and antiphospholipid antibody syndrome.

To investigate the effect of inflammation on the fetal thymus-thoracic ratio (TTR) in pregnant women with systemic lupus erythematosus (SLE), Sjögren's syndrome (SS) and antiphospholipid antibody syndrome (APS). This prospective case-control study included 45 pregnant women with SLE, SS, and APS and 90 gestational age-matched healthy pregnant women between 24 and 37 gestational weeks. The ratio of the anteroposterior fetal thymus length to the transverse mediastinal length was calculated as the TTR in the study groups. Fetal TTR was significantly lower in the case group (p < 0.001). Fetal TTR in the APS group was significantly lower than SS group (p = 006). The patients using hydroxychloroquine (HCQ) had significantly higher fetal TTR compared to patients not using HCQ (p = 0.004). A moderate negative correlation was found between the disease duration and fetal TTR (r = - 0.552, p < 0.001). In predicting admission to the neonatal intensive unit care (NICU), a value of 0.31 was found for the fetal TTR with a sensitivity of 83.3% and a specificity of 69% CONCLUSION: Maternal inflammation in pregnancies with autoimmune diseases may affect the intrauterine milieu of the fetus and cause a lower fetal TTR. Additionally, the lower level of fetal TTR may be more effective and beneficial for the clinician if combined with other risk factors in predicting NICU admission.

Diagnostic value of ultrasound evaluation of major salivary glands for Sjögren’s syndrome based on the novel OMERACT scoring system

ObjectiveThe novel Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system was used to evaluate the diagnostic effectiveness of major salivary gland ultrasonography (SGUS) for Sjögren's syndrome (SS). Materials and methodsSGUS was performed on the parotid glands (PGs) and submandibular glands of 242 patients (145 patients with SS and 97 patients without SS) using the OMERACT scoring system (grade 0–3). We also evaluated the association of SGUS scores with unstimulated whole salivary flow rate (UWSF), stimulated whole salivary flow rate (SWSF), and labial salivary gland biopsy (LSGB) results. ResultsThe SGUS scores were significantly higher for the SS group than for the non-SS group (p < 0.001). Using a cutoff value of 8 for the total score yielded the highest sensitivity (76%), specificity (90%), and area under the receiver operating characteristic curve (AUC, 0.828). The correlation between SGUS scores and salivary gland function was moderate to good. A cutoff value of 10 for the total score was more effective in predicting SWSF outcomes than UWSF outcomes (sensitivity: 73% > 58%, specificity: 98% > 87%, and AUC: 0.856 > 0.723). The association of OMERACT scores with LSGB results was fair to moderate. Among 61 anti-SSA-negative patients, 17 had positive PG scores (including ten SS and seven non-SS patients), and 44 had negative PG scores (including 37 non-SS and seven SS patients). ConclusionThe OMERACT scoring system had good sensitivity and excellent specificity, demonstrating excellent diagnostic potential for SS and efficacy in assessing salivary gland function. Negative SGUS results may help reduce unnecessary biopsies in anti-SSA-negative patients.

Tear levels of IL-7, IL-1α, and IL-1β may differentiate between IgG4-related disease and Sjögren's syndrome.

We aim to assess and compare a cytokine and chemokine profile in tears from patients with IgG4-related disease (IgG4-RD) and Sjögren's syndrome (SS), and to see if this profile could aid in differentiating these two diseases. We included 10 patients with IgG4-RD who met the Comprehensive Diagnostic Criteria for IgG4-RD and 17 patients who met the AECG criteria for primary SS. The Schirmer-I test was carried out using two standardized sterile tear strips, which were then immediately frozen at - 86°C until assayed. The tears were extracted from the strips after they had been defrosted using a buffer containing 0.5M NaCl and 0.5% Tween-20. The amounts (pg/ml) of the following cytokines and chemokines were then measured using luminometry: IFN-γ, TNF-α, G-CSF, IL-1-α, IL-1β, IL-4, IL-7, IL-12p40, IL-12p70, IL-13, IL-17A, CCL2, CCL3, CCL4, CCL11, and CXCL10. In the IgG4-RD group, seven patients had lacrimal gland involvement, five had dry eye symptoms, and six had a positive Schirmer-I test. In the SS group, 16 (94.1%) had dry eyes and all had a positive Schirmer-I test. We were able to differentiate between both diseases using levels of IL-7, IL-1α, and IL-1β; in particular, the IL-7/IL-1α and IL-7/IL-1β ratios had the best discriminatory potential, with cut-off values of 0.32 (AUC: 0.93, sensitivity: 94%, specificity: 80%, p = 0.0003) and 12.55 (AUC: 0.96, sensitivity: 94%, specificity: 90%, p = 0.0001), respectively. Our results suggest that IL-7, IL-1α, and IL-1β tear levels could help differentiate IgG4-RD from SS. Key Points • The lacrimal gland is frequently involved in IgG4-RD and SS. This characteristic makes both diseases mimics of one another. • Patients with IgG4-RD and SS have different profiles of tear cytokines and chemokines. • Tear IL-7, IL-1α, and IL-1β levels may serve as helpful biomarkers in separating IgG4-RD from SS.

Effect of maternal autoimmune diseases on fetal pulmonary artery Doppler indices: A case-control study.

To compare the fetal pulmonary artery Doppler indices of pregnant women with autoimmune diseases such as systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and antiphospholipid syndrome (APS) with healthy pregnant women. Thirty-nine pregnancies were included in the case group, 19 of them SLE, 12 with SS, and eight with APS. The gestational age-matched 54 healthy pregnant women were included in the control group. Peak systolic velocity, time-averaged velocity, systolic/diastolic ratio, pulsatility index, resistance index, acceleration time (AT), ejection time (ET), and AT/ET ratio were obtained from pulmonary artery waveform by using spectral Doppler ultrasound. Significantly shorter AT and lower AT/ET ratio were detected in the case group (p=<.001, p=<.001, respectively). The shortening of AT and decreasing of the AT/ET ratio were more predominant in the APS group. However, there was no significant difference between the SLE, SS, and APS groups in fetal pulmonary artery Doppler indices. Also, a moderate correlation was found between maternal disease duration (years) and fetal pulmonary artery AT (r=-.516, p=.001) and AT/ET ratio (r=-.558, p=<.001). Fetal pulmonary artery Doppler indices may be affected in maternal autoimmune diseases. Further studies are needed to evaluate fetal pulmonary Doppler indices such as AT and AT/ET ratio to predict neonatal respiratory morbidity and lung maturation in pregnant women with SLE, SS, and APS.

Exosome-Derived microRNAs from Mouthrinse Have the Potential to Be Novel Biomarkers for Sjögren Syndrome.

Sjögren syndrome (SS) is diagnosed based on invasive tissue biopsies and blood sampling. Therefore, a novel non-invasive and simple inspection diagnostic marker of SS is required. Here, we identified exosome-derived microRNAs (miRNAs) as biomarkers for SS using non-invasive mouthrinse samples collected from patients with SS and healthy volunteers. We compared miRNAs derived from exosomes in mouthrinse samples from the two groups using microarrays and real-time polymerase chain reaction (PCR) and identified 12 miRNAs as biomarker candidates. The expression ratios of four miRNAs were significantly increased in the SS group compared to the control group. Logistic regression analysis revealed a more significant influence of miR-1290 and let-7b-5p in the SS group than that in the control group. We combined these miRNAs to create a diagnostic prediction formula using logistic regression analysis. The combination of miR-1290 and let-7b-5p distinguished SS from the control samples with an AUC, sensitivity, specificity, positive predictive value, and negative predictive value of 0.856, 91.7%, 83.3%, 84.6%, and 90.9%, respectively. These results indicated that an increased ratio of these miRNAs could serve as a novel and non-invasive diagnostic marker for SS. This is the first report of diagnosis and screening of SS by adopting a non-invasive method using mouthrinse.

Clinical significance of autoantibodies against ubiquitin carboxyl hydrolase L1 epitopes in the screening and diagnosis of Sjögren syndrome

Objective: To study the clinical significance of autoantibodies against different ubiquitin carboxyl hydrolase L1 (UCH-L1) epitopes in Sjogren syndrome (SS). Methods: The serum levels of different UCH-L1 epitope autoantibodies in 98 SS patients [SS group, 17 males and 81 females, aged (49.1±12.3) years] in the Fifth Affiliated Hospital of Zhengzhou University and Peking University People's Hospital from January 2017 to January 2020 and 37 healthy controls [control group, 6 males and 31 females, aged (46.3±5.8) years] were determined by enzyme-linked immunosorbent assay (ELISA). Three potential epitopes of UCH-L1 protein were analyzed and synthesized and anti-UCH-L1203-214 and anti-UCH-L158-69 antibodies were studied between the two groups. The levels of the two anti-UCH-L1 antibodies in the two groups were compared. The correlation between the levels of UCH-L1 antibodies and clinical data of SS patients were analyzed by Pearson correlation analysis. Results: The serum levels of anti-UCH-L1203-214 and anti-UCH-L158-69 antibody in SS patients were significantly higher than those in healthy controls (HCs) (anti-UCH-L1203-214: 108.2±54.3 vs 78.9±25.8, P<0.001, anti-UCH-L158-69: 86.8±33.3 vs 60.4±21.5, P<0.001). The positive rates of anti-UCH-L1203-214 and anti-UCH-L158-69 antibodies in serums of SS patients were 27.6 % (27/98) and 25.5% (25/98), and those in HCs were 2.7%(1/37) and 5.4 %(2/37), respectively. In SS patients with positive serum anti-UCH-L158-69 antibody, the levels of IgG, γ globulin and rheumatoid factor (RF) and anti-SS-related antigen B (anti-SSB) antibody positive rate were all significantly higher than those in patients with negative antibody (all P<0.05). In SS patients with negative antinuclear antibody (ANA), anti-RNA binding protein (anti-RNP) antibody, anti-SS-related antigen A (anti-SSA) antibody and anti-SSB antibody, the positive rates of anti-UCH-L1203-214 antibody was 32.1%(9/28), 27.2%(25/92), 36.4%(12/33), 28.6%(18/63), respectively; and the positive rates of anti-UCH-L158-69 antibody was 21.4%(6/28), 30.4%(28/92), 30.3%(10/33), 20.6%(13/63), respectively. The level of serum anti-UCH-L1203-214 antibody in SS patients was positively correlated with the IgA level (r=0.21, P=0.024). The level of anti-UCH-L158-69 antibody in SS patients was positively correlated with the levels of γ-globulin, IgG and RF (r=0.35, 0.33, 0.32, all P<0.01). Conclusion: Autoantibodies against UCH-L1 epitopes are correlated with some clinical parameters of SS patients, which is of promising significance in the screening and diagnosis of SS.

Diagnostic Performances of Ultrasound Evaluation of Major Salivary Glands According to the 2019 Outcome Measures in Rheumatology Ultrasound Scoring System.

To evaluate the diagnostic performance of ultrasound examination of the salivary glands (US-SG) according to the 2019 Outcome Measures in Rheumatology (OMERACT) US scoring system for Sjögren's syndrome (SS). The present work was a retrospective study based on a multicentric cohort with SS/sicca syndrome. The American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2016 classification criteria for SS (a score of ≥4 without ocular staining score), the American-European Consensus Group (AECG) 2002 classification criteria, and clinician experts were considered as reference standards for diagnosis of SS. An OMERACT score of ≥2 according to 2 independent readers defined the diagnosis of SS based on US-SG assessment. Diagnostic performances and interobserver reproducibility of US-SG were assessed. Forty-two patients fulfilling the ACR/EULAR 2016 criteria for SS were compared to 30 control subjects with sicca syndrome. Twenty-five patients were diagnosed as having SS according to US-SG evaluation, and they were more frequently observed in the SS group (52.5%) than in the control group (10.0%) (P < 0.001). US-SG showed an area under the curve (AUC) of 0.751 (95% confidence interval [95% CI] 0.621, 0.882) for the diagnosis of SS (ACR/EULAR 2016 classification). The inclusion of US-SG in the ACR/EULAR 2016 classification improved sensitivity (91.5% versus 89.4%) with limited decrease of specificity (96.0% versus 100%) and with an AUC of 0.975 (95% CI 0.945, 1.00). Similar results were observed when US-SG was included in the AECG 2002 classification criteria. Interobserver reproducibility of a score of ≥2 according to the 2019 OMERACT US scoring system for SS diagnosis was good (κ=0.73 [95% CI 0.64, 0.81]). Histologic lymphocyte infiltration of the minor salivary glands was associated with the OMERACT grading of US-SG. The present study confirms the good specificity of the 2019 OMERACT US classification measures of US-SG for the diagnosis of SS and its feasibility in daily practice.

In vivo confocal microscopic study of corneal innervation in Sjögren's Syndrome with or without small fiber neuropathy

PurposeTo study changes in the subbasal nerve plexus by In vivo confocal microscopy (IVCM) in Sjögren's Syndrome (SS) with or without associated Small Fiber Neuropathy (SFN), in order to prevent diagnostic delay. MethodsSeventy-one patients with SS, including 19 with associated SFN, 20 healthy volunteers and 20 patients with Meibomian gland dysfunction (MGD) were included in this retrospective case-control study. IVCM was used to investigate subbasal nerve plexus density and morphology. ResultsCorneal sensitivity as evaluated with the Cochet-Bonnet aesthesiometer was significantly reduced in the SS group versus the control group (P = 0.026) and the MGD group (P = 0.037). The number of inflammatory cells was significantly increased in the SS group to 86.2 ± 82.1 cells/mm2 compared to the control group (P < 0.001). The density of the subbasal nerve plexus was significantly reduced to 16.7 ± 6.5 mm/mm2 in the SS group compared to the control group (P < 0.005) and the MGD group (P = 0.042). The tortuosity of the nerves in the SS group was significantly increased compared to the control group (P < 0.001) and the MGD group (P = 0.025). The average number of subbasal nerve plexus neuromas was significantly increased in the SS group compared to the control group (P = 0.001), with a significant increase in the average number of neuromas in SS patients with associated SFN compared to SS patients without SFN (P = 0.008). ConclusionIVCM can be useful to detect corneal nerve changes in SS patients and may allow earlier diagnosis of the disease and to consider new therapeutic approaches.