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Objective·To study the clinical features of two primary Sjögren's syndrome (pSS) patients with neurological symptoms as initial manifestations and review the related literature.Methods·The clinical data, response to treatment as well as prognosis of 2 cases were analyzed and followed up.Results·Case 1, female, initially presented progressive gait instability and distal sensory impairment at the age of 50. Clinical manifestations included spastic gait, sensory ataxia, conduction fascicular sensory impairment, as well as urination and defecation dysfunction. At the age of 58, this patient was unable to walk independently. The laboratory findings revealed a positive result for anti-nuclear antibody with a titer of 1∶1 000, anti-Sjögren's syndrome A (SSA)/Ro-52, anti-SSA/Ro-60, and anti-centromere antibodies. Labial salivary gland biopsy showed lymphocytes and plasma cells infiltration into the glandular tissues, interstitium, and lobules, with 2 foci/4 mm2 (lymphocytes >50). The cranial magnetic resonance imaging exhibited bilateral symmetric hyperintensity in the brainstem, characterized by the "snake-eye sign". Electromyography examination revealed axonal impairment of the right peroneal nerve. The patient was treated with high-dose corticosteroid therapy in combination with immunosuppressants. She experienced remarkable improvement. After three months, she was able to walk with aids and take care of herself in daily life. Case 2, female, presented spasmodic torticollis since the age of 81 with unknown reason. She had a history of mild mucosal dryness of mouth and eyes, and painful knee for one year. Laboratory findings revealed positive results for anti-SSA/Ro-52 and anti-SSA/Ro-60 antibodies, as well as hemoglobin of 86 g/L. Labial salivary gland biopsy demonstrated partial atrophy of the acini and the presence of 2 foci/4 mm2 of lymphocytes and plasma cells infiltration into the stroma (lymphocytes>50). Electromyography examination showed reduced conduction velocity in the right median nerve. She got a significant relief after the treatment of immunosuppressants, antispasmodics, and muscle relaxants.Conclusion·Patients presenting initial symptoms such as complex forms of spastic paraplegia and cervical dystonia expand the clinical spectrum of pSS. In clinical practice, it is important to distinguish neurological involvement secondary to pSS from other primary neurological disorders. For patients with neurological impairments but without apparent etiology, it is crucial to screen relevant series of autoimmune antibodies.

Evidence of gut microbiota disruption for numerous autoimmune diseases has accumulated. Recently, the relationship between the microbiota and primary Sjögren's disease has been increasingly investigated but has yet to be systematically elucidated. Therefore, a meta-analysis of publications dealing on topic was conducted. Case–control studies comparing primary Sjögren's syndrome patients and healthy controls (HCs) were systematically searched in nine databases from inception to March 1, 2023. The primary result quantitatively evaluated in this meta-analysis was the α-diversity. The secondary results qualitatively extracted and analyzed were the β-diversity and relative abundance. In total, 22 case–control studies covering 915 pSS patients and 2103 HCs were examined. The quantitative analysis revealed a slight reduction in α-diversity in pSS patients compared to HCs, with a lower Shannon–Wiener index (SMD = − 0.46, (− 0.68, − 0.25), p < 0.0001, I2 = 71%), Chao1 richness estimator (SMD = − 0.59, (− 0.86, − 0.32), p < 0.0001, I2 = 81%), and ACE index (SMD = − 0.92, (− 1.64, − 0.19), p = 0.01, I2 = 86%). However, the Simpson index (SMD = 0.01, (− 0.43, 0.46) p = 0.95, I2 = 86%) was similar in the two groups. The β-diversity significantly differed between pSS patients and HCs. Variations in the abundance of specific microbes and their metabolites and potential functions contribute to the pSS pathogenesis. Notably, the abundance of the phylum Firmicutes decreased, while that of Proteobacteria increased. SCFA-producing microbes including Ruminococcaceae, Lachnospiraceae, Faecalibacterium, Butyricicoccus, and Eubacterium hallii were depleted. In addition to diversity, the abundances of some specific microbes were related to clinical parameters. According to this systematic review and meta-analysis, gut microbiota dysbiosis, including reduced diversity, was associated with proinflammatory bacterium enrichment and anti-inflammatory bacterium depletion in pSS patients. Further research on the relationship between the gut microbiota and pSS is warranted. [ABSTRACT FROM AUTHOR]

Objectives: To explore clinical and laboratory characteristics of primary Sjögren's syndrome (pSS) complicated with interstitial lung disease (ILD) and investigate the risk factors for respiratory infections in pSS-ILD. Methods: A cohort of 162 pSS-ILD patients in Peking University People's Hospital from 2015 to 2020 were included, and all medical records were completely collected. We screened 53 patients suffering from respiratory infections as study cases, compared with 109 age- and sex-matched controls. Differences between infection group and control group were compared. Univariate and multivariate binary logistic regression tests were conducted to identify potential risk factors for respiratory infections in pSS-ILD patients. Results: Among 162 pSS-ILD patients, 32.72% (53/162) suffered from respiratory infections. The most frequent type of ILD was nonspecific interstitial pneumonia (32.08%, 51/159), and the most common type of pathogen was bacteria (64.25%, 34/53). Infection group showed higher levels of ESSDAI (P < 0.001), CRP (P < 0.001), ESR (P = 0.003), and C3 (P = 0.020) but lower level of DLCO-SB (P = 0.015). Univariate logistic model revealed that PAH and the use of glucocorticoid increased infection risk in pSS-ILD patients. On multivariate logistic regression analysis, PAH (OR = 3.993, 95% CI = 1.192–13.373, P = 0.025) and severe reduction of DLCO (DLCO-SB < 40%, OR = 4.625, 95% CI = 1.281–16.702, P = 0.019) were significantly associated with increased risk of respiratory infections in pSS-ILD patients. Conclusion: Among pSS-ILD patients, the most frequent type of ILD was nonspecific interstitial pneumonia. In patients with infection, bacteria were the most common pathogen. Higher levels of ESSDAI, CRP, ESR, and C3 may be correlated with increased infection risk. PAH and reduction of DLCO were identified as independent risk factors. Key Points • ILD and infectious diseases severely affect pSS patient conditions. • Higher levels of ESSDAI, CRP, ESR, and C3 may be correlated with increased infection risks in pSS-ILD. • PAH and reduction of DLCO were identified as independent risk factors for lower respiratory infection. [ABSTRACT FROM AUTHOR]

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Abstract Objectives The aim of this study was to investigate serum biomarkers linked to primary Sjögren's syndrome (pSS)-associated interstitial lung disease (ILD). Methods 69 pSS patients were consecutively enrolled and evaluated via quantitative ILD scoring based on high-resolution computed tomography (HRCT). Biomarkers of interest were assessed by multiplex enzyme-linked immunosorbent assays (ELISAs). Results Among consecutively enrolled patients with pSS, the presence of pSS–ILD was 50% based on the presence of radiographically defined interstitial lung abnormalities (ILA) meeting specified criteria for mild/moderate (ILA 2) or severe (ILA 3) disease. Age, immunoglobulin M (IgM), C-reactive protein (CRP), and serum levels of eotaxin/CCL11, Krebs von den Lungen-6 (KL-6), TNFα, and TGFα were significantly higher in the combined pSS–ILD group (ILA 2 + ILA 3) than in the pSS–no-ILD and pSS–indeterminate ILD groups (ILA 0 and ILA 1, respectively) in unadjusted analyses (p

Primary Sjögren's Syndrome (pSS) is a systemic autoimmune disease that primarily attacks the lacrimal and salivary glands, resulting in impaired secretory function characterized by xerostomia and xerophthalmia. Patients with pSS have been shown to have impaired salivary gland innervation and altered circulating levels of neuropeptides thought to be a cause of decreased salivation, including substance P (SP). Using Western blot analysis and immunofluorescence studies, we examined the expression levels of SP and its preferred G protein-coupled TK Receptor 1 (NK1R) and apoptosis markers in biopsies of the minor salivary gland (MSG) from pSS patients compared with patients with idiopathic sicca syndrome. We confirmed a quantitative decrease in the amount of SP in the MSG of pSS patients and demonstrated a significant increase in NK1R levels compared with sicca subjects, indicating the involvement of SP fibers and NK1R in the impaired salivary secretion observed in pSS patients. Moreover, the increase in apoptosis (PARP-1 cleavage) in pSS patients was shown to be related to JNK phosphorylation. Since there is no satisfactory therapy for the treatment of secretory hypofunction in pSS patients, the SP pathway may be a new potential diagnostic tool or therapeutic target. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate serum biomarkers linked to primary Sjögren's syndrome (pSS)-associated interstitial lung disease (ILD). Methods: 69 pSS patients were consecutively enrolled and evaluated via quantitative ILD scoring based on high-resolution computed tomography (HRCT). Biomarkers of interest were assessed by multiplex enzyme-linked immunosorbent assays (ELISAs). Results: Among consecutively enrolled patients with pSS, the presence of pSS–ILD was 50% based on the presence of radiographically defined interstitial lung abnormalities (ILA) meeting specified criteria for mild/moderate (ILA 2) or severe (ILA 3) disease. Age, immunoglobulin M (IgM), C-reactive protein (CRP), and serum levels of eotaxin/CCL11, Krebs von den Lungen-6 (KL-6), TNFα, and TGFα were significantly higher in the combined pSS–ILD group (ILA 2 + ILA 3) than in the pSS–no-ILD and pSS–indeterminate ILD groups (ILA 0 and ILA 1, respectively) in unadjusted analyses (p < 0.05 for all variables). A binary logistic regression model revealed that disease duration and KL-6 levels were associated with the presence of pSS–ILD (p < 0.05). Complementary least absolute shrinkage and selection operator (LASSO) modeling showed that age, KL-6, and TNF-α effectively differentiated pSS–ILD (ILA 2 + ILA3) from pSS without ILD (ILA 0 + ILA 1), with an area under the curve (AUC) of 0.883 (p value < 0.0001). Conclusions: Patient age, disease duration, and serum levels of both KL-6 and TNFα were the most discriminating factors associated with the presence of ILD in our pSS patients. Higher levels of CRP, IgM, eotaxin, TGFα, and TNFα should also prompt the search for occult as well as clinically evident lung involvement based on statistically significant univariate associations with pSS–ILD. Clinical trial registration: None. [ABSTRACT FROM AUTHOR]

Background: Primary Sjögren's syndrome (pSS) and breast cancer are a highly prevalent autoimmune disease and malignancy, respectively, both occurring predominantly in females. Whether there is a link between these two diseases is uncertain. We conducted a systematic review and meta-analysis to investigate the risk, incidence, and mortality of breast cancer in patients with pSS. Methods: We systematically searched Embase, PubMed, and Web of Science on January 31, 2022 to identify the study that assessed risk, incidence, or mortality of breast cancer in pSS. The fixed or random-effects models were applied to pool the effect estimates based on heterogeneity measured by Cochran's Q-test and Higgins' I². Results: Ten studies involving 725,805 participants and 64,836 pSS patients were included in our analysis. The pooled result showed that, overall, pSS was not associated with the risk (SIR=0.92, 95%CI: 0.66-1.29, P=0.646) and mortality (HR = 0.78, 95%CI: 0.26-2.34, P = 0.664) of breast cancer; however, when stratified by geographic region, we found that patients with pSS in Asian countries (SIR=1.32, 95%CI: 1.10-1.58, P=0.003) and Argentina (SIR=3.76, 95%CI: 1.04-9.45, P=0.019) had an elevated risk of breast cancer, while pSS in Europe was associated with a reduced risk (SIR=0.61, 95%CI: 0.51-0.73, P<0.001). The pooled result from 28,635 female pSS patients indicated that the incidence of breast cancer was 2.15 (95% CI: 1.33-3.50) per 1000 person/years. Conclusion: This study suggests that there may be geographical differences in the association between pSS and breast cancer risk; patients with pSS in European countries are associated with a lower risk of breast cancer, while Asia and Argentina are the opposite. Future research is needed to further characterize the effect of pSS on breast cancer risk and the pathophysiological mechanisms underlying this association to unravel the complex relationship between the two. [ABSTRACT FROM AUTHOR]

Introduction: Increased CCL5 expression and CD8 T cells have been shown to be pivotal regulators of immunopathology in primary Sjögren's syndrome (pSS) and pSS-like disease. Increased CCL5 expression by CCR9+ CD4 T cells has previously been implicated as a contributor to immunopathology in pSS. The role of CD8 T cells and in particular CCR9+ CD8 T cells and their potential to secrete CCL5 has not previously been studied in pSS. In this study we investigated both CCR9 and CCL5 expression by CD8 T cells in pSS patients compared to healthy controls (HC). Methods: CCR9 expression on CD8 T cells from peripheral blood was compared between patients with pSS and HC by flow cytometry. Intracellular CCL5 expression by naive, memory and effector CCR9- and CCR9+ CD8 T cells was assessed. In addition, the capacity and pace of CCL5 release upon T cell activation was determined for all subsets and compared with CD4 T cells. Results: The frequency of circulating CCR9+ CD8 T cells in pSS patients is increased compared to HC. Antigen-experienced CD8 T cells, especially CCR9+ effector CD8 T cells, express the highest CCL5 levels, and release the highest levels of CCL5 upon activation. Memory and effector CD8 T cells of pSS patients express significantly less CCL5 and subsequently release less CCL5 upon stimulation compared to HC. CCR9+ CD8 T cells rapidly release CCL5 and significantly more than CCR9+ CD4 T cells. Conclusion: CCR9+ CD8 T cells express more CCL5 than CCR9- CD8 T cells. CCL5 is rapidly released upon activation, resulting in reduced intracellular expression. Reduced CCL5 expression by an elevated number of antigen-experienced CCR9-expressing CD8 T cells in pSS patients points towards increased release in vivo. This suggests that CCL5 release by CCR9+ CD8 T cells contributes to immunopathology in pSS. [ABSTRACT FROM AUTHOR]

IntroductionIncreased CCL5 expression and CD8 T cells have been shown to be pivotal regulators of immunopathology in primary Sjögren’s syndrome (pSS) and pSS-like disease. Increased CCL5 expression by CCR9+ CD4 T cells has previously been implicated as a contributor to immunopathology in pSS. The role of CD8 T cells and in particular CCR9+ CD8 T cells and their potential to secrete CCL5 has not previously been studied in pSS. In this study we investigated both CCR9 and CCL5 expression by CD8 T cells in pSS patients compared to healthy controls (HC).MethodsCCR9 expression on CD8 T cells from peripheral blood was compared between patients with pSS and HC by flow cytometry. Intracellular CCL5 expression by naive, memory and effector CCR9- and CCR9+ CD8 T cells was assessed. In addition, the capacity and pace of CCL5 release upon T cell activation was determined for all subsets and compared with CD4 T cells.ResultsThe frequency of circulating CCR9+ CD8 T cells in pSS patients is increased compared to HC. Antigen-experienced CD8 T cells, especially CCR9+ effector CD8 T cells, express the highest CCL5 levels, and release the highest levels of CCL5 upon activation. Memory and effector CD8 T cells of pSS patients express significantly less CCL5 and subsequently release less CCL5 upon stimulation compared to HC. CCR9+ CD8 T cells rapidly release CCL5 and significantly more than CCR9+ CD4 T cells.ConclusionCCR9+ CD8 T cells express more CCL5 than CCR9- CD8 T cells. CCL5 is rapidly released upon activation, resulting in reduced intracellular expression. Reduced CCL5 expression by an elevated number of antigen-experienced CCR9-expressing CD8 T cells in pSS patients points towards increased release in vivo. This suggests that CCL5 release by CCR9+ CD8 T cells contributes to immunopathology in pSS.

Primary Sjögren’s Syndrome (pSS) is a systemic autoimmune disease that primarily attacks the lacrimal and salivary glands, resulting in impaired secretory function characterized by xerostomia and xerophthalmia. Patients with pSS have been shown to have impaired salivary gland innervation and altered circulating levels of neuropeptides thought to be a cause of decreased salivation, including substance P (SP). Using Western blot analysis and immunofluorescence studies, we examined the expression levels of SP and its preferred G protein-coupled TK Receptor 1 (NK1R) and apoptosis markers in biopsies of the minor salivary gland (MSG) from pSS patients compared with patients with idiopathic sicca syndrome. We confirmed a quantitative decrease in the amount of SP in the MSG of pSS patients and demonstrated a significant increase in NK1R levels compared with sicca subjects, indicating the involvement of SP fibers and NK1R in the impaired salivary secretion observed in pSS patients. Moreover, the increase in apoptosis (PARP-1 cleavage) in pSS patients was shown to be related to JNK phosphorylation. Since there is no satisfactory therapy for the treatment of secretory hypofunction in pSS patients, the SP pathway may be a new potential diagnostic tool or therapeutic target.

Animal models of autoimmunity and human genetic association studies indicate that the dysregulation of B-cell receptor (BCR) signaling is an important driver of autoimmunity. We previously showed that in circulating B cells from primary Sjögren's syndrome (pSS) patients with high systemic disease activity, protein expression of the BCR signaling molecule Bruton's tyrosine kinase (BTK) was increased and correlated with T-cell infiltration in the target organ. We hypothesized that these alterations could be driven by increased B-cell activating factor (BAFF) levels in pSS. Here, we investigated whether altered BCR signaling was already present at diagnosis and distinguished pSS from non-SS sicca patients. Using (phospho-)flow cytometry, we quantified the phosphorylation of BCR signaling molecules, and investigated BTK and BAFF receptor (BAFFR) expression in circulating B cell subsets in an inception cohort of non-SS sicca and pSS patients, as well as healthy controls (HCs). We found that both BTK protein levels and BCR signaling activity were comparable among groups. Interestingly, BAFFR expression was significantly downregulated in pSS, but not in non-SS sicca patients, compared with HCs, and correlated with pSS-associated alterations in B cell subsets. These data indicate reduced BAFFR expression as a possible sign of early B cell involvement and a diagnostic marker for pSS. [ABSTRACT FROM AUTHOR]

Background: Primary Sjogren's syndrome (pSS) is a slowly progressive, inflammatory autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands. It becomes more recognized that morphology alterations of epithelial mitochondria are involved in altered cellular bioenergetics in pSS patients. The integrated analysis of the mitochondrial role in the pathogenesis and aberrant immune microenvironment in pSS remains unknown. Methods: The mitochondria-related genes and gene expression data were downloaded from the MitoMiner, MitoCarta, and NCBI GEO databases. We performed novel transcriptomic analysis and constructed a network between the mitochondrial function and immune microenvironment in pSS-salivary glands by computer-aided algorithms. Subsequently, real-time PCR was performed in clinical samples in order to validate the bioinformatics results. Histological staining and transmission electron microscopy (TEM) were further studied on labial salivary gland samples of non-pSS and pSS patients characterized for mitochondria-related phenotypic observation in the different stages of the disease. Results: The bioinformatic analysis revealed that the expression of several mitochondria-related genes was altered in pSS. Quantitative real-time PCR showed that four hub genes, CD38 , CMPK2 , TBC1D9 , and PYCR1 , were differentially expressed in the pSS clinical samples. These hub genes were associated with the degree of immune cell infiltration in salivary glands, the mitochondrial respiratory chain complexes, mitochondrial metabolic pathway in gluconeogenesis, TCA cycle, and pyruvate/ketone/lipid/amino acid metabolism in pSS. Clinical data revealed that the gene expression of fission (Fis1 , DRP1 , and MFF) and fusion (MFN1 , MFN2 , and OPA1) was downregulated in pSS samples, consistent with the results from the public validation database. As the disease progressed, cytochrome c and Bcl-2 proteins were regionally distributed in salivary glands from pSS patients. TEM revealed cytoplasmic lipid droplets and progressively swollen mitochondria in salivary epithelial cells. Conclusion: Our study revealed cross talk between mitochondrial dysfunction and the immune microenvironment in salivary glands of pSS patients, which may provide important insights into SS clinical management based on modulation of mitochondrial function. [ABSTRACT FROM AUTHOR]

BackgroundPrimary Sjogren’s syndrome (pSS) is a slowly progressive, inflammatory autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands. It becomes more recognized that morphology alterations of epithelial mitochondria are involved in altered cellular bioenergetics in pSS patients. The integrated analysis of the mitochondrial role in the pathogenesis and aberrant immune microenvironment in pSS remains unknown.MethodsThe mitochondria-related genes and gene expression data were downloaded from the MitoMiner, MitoCarta, and NCBI GEO databases. We performed novel transcriptomic analysis and constructed a network between the mitochondrial function and immune microenvironment in pSS-salivary glands by computer-aided algorithms. Subsequently, real-time PCR was performed in clinical samples in order to validate the bioinformatics results. Histological staining and transmission electron microscopy (TEM) were further studied on labial salivary gland samples of non-pSS and pSS patients characterized for mitochondria-related phenotypic observation in the different stages of the disease.ResultsThe bioinformatic analysis revealed that the expression of several mitochondria-related genes was altered in pSS. Quantitative real-time PCR showed that four hub genes, CD38, CMPK2, TBC1D9, and PYCR1, were differentially expressed in the pSS clinical samples. These hub genes were associated with the degree of immune cell infiltration in salivary glands, the mitochondrial respiratory chain complexes, mitochondrial metabolic pathway in gluconeogenesis, TCA cycle, and pyruvate/ketone/lipid/amino acid metabolism in pSS. Clinical data revealed that the gene expression of fission (Fis1, DRP1, and MFF) and fusion (MFN1, MFN2, and OPA1) was downregulated in pSS samples, consistent with the results from the public validation database. As the disease progressed, cytochrome c and Bcl-2 proteins were regionally distributed in salivary glands from pSS patients. TEM revealed cytoplasmic lipid droplets and progressively swollen mitochondria in salivary epithelial cells.ConclusionOur study revealed cross talk between mitochondrial dysfunction and the immune microenvironment in salivary glands of pSS patients, which may provide important insights into SS clinical management based on modulation of mitochondrial function.

Background: Mitochondria are the metabolic hubs of cells, regulating energy production and antigen presentation, which are essential for activation, proliferation, and function of immune cells. Recent evidence indicates that mitochondrial antigen presentation may have an impact on diseases such as Parkinson's disease (PD) and autoimmune diseases. However, there is limited knowledge about the mechanisms that regulate the presentation of mitochondrial antigens in these diseases., Methods: In the current study, RNA sequencing was performed on labial minor salivary gland (LSG) from 25 patients with primary Sjögren's syndrome (pSS) and 14 non-pSS aged controls. Additionally, we obtained gene expression omnibus datasets associated with PD patients from NCBI Gene Expression Omnibus (GEO) databases. Single-sample Gene Set Enrichment Analysis (ssGSEA), ESTIMATE and Spearman correlations were conducted to explore the association between mitochondrial related genes and the immune system. Furthermore, we applied weighted Gene Co-expression Network Analysis (WGCNA) to identify hub mitochondria-related genes and investigate the correlated networks in both diseases. Single cell transcriptome analysis, immunohistochemical (IHC) staining and quantitative real-time PCR (qRT-PCR) were used to verify the activation of the hub mitochondria-related pathway. Pearson correlations and the CIBERSORT algorithms were employed to further reveal the correlation between hub mitochondria-related pathways and immune infiltration., Results: The transcriptome analysis revealed the presence of overlapping mitochondria-related genes and mitochondrial DNA damage in patients with pSS and PD. Reactive oxygen species (ROS), the senescence marker p53, and the inflammatory markers CD45 and Bcl-2 were found to be regionally distributed in LSGs of pSS patients. WGCNA analysis identified the STING pathway as the central mitochondria-related pathway closely associated with the immune system. Single cell analysis, IHC staining, and qRT-PCR confirmed the activation of the STING pathway. Subsequent, bioinformatic analysis revealed the proportion of infiltrating immune cells in the STING-high and STING-low groups of pSS and PD. Furthermore, the study demonstrated the association of the STING pathway with innate and adaptive immune cells, as well as functional cells, in the immune microenvironment of PD and pSS., Conclusion: Our study uncovered a central pathway that connects mitochondrial dysfunction and the immune microenvironment in PD and pSS, potentially offering valuable insights into therapeutic targets for these conditions., Competing Interests: Declaration of competing interest The authors declare that the current research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Organizing pneumonia (OP) is a pulmonary disease histopathologically characterized by plugs of loose connective tissue in distal airways. The clinical and radiological presentations are not specific and they usually require a biopsy confirmation. This paper presents the case of a patient with a pulmonary opacity sampled with a combined technique of ultrathin bronchoscopy and cone-beam CT. A 64-year-old female, a former smoker, was admitted to the hospital of Reggio Emilia (Italy) for exertional dyspnea and a dry cough without a fever. The history of the patient included primary Sjögren Syndrome interstitial lung disease (pSS-ILD) characterized by a non-specific interstitial pneumonia (NSIP) radiological pattern; this condition was successfully treated up to 18 months before the new admission. The CT scan showed the appearance of a right lower lobe pulmonary opacity of an uncertain origin that required a histological exam for the diagnosis. The lung lesion was difficult to reach with traditional bronchoscopy and a percutaneous approach was excluded. Thus, cone-beam CT, augmented fluoroscopy and ultrathin bronchoscopy were chosen to collect a tissue sample. The histopathological exam was suggestive of OP, a condition occurring in 4–11% of primary Sjögren Syndrome cases. This case showed that, in the correct clinical and radiological context, even biopsies taken with small forceps can lead to a diagnosis of OP. Moreover, it underlined that the combination of multiple advanced technologies in the same procedure can help to reach difficult target lesions, providing proper samples for a histological diagnosis.

BackgroundPrimary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease of the exocrine glands characterized by specific pathological features. Previous studies have pointed out that salivary glands from pSS patients express a unique profile of cytokines, adhesion molecules, and chemokines compared to those from healthy controls. However, there is limited evidence supporting the utility of individual markers for different stages of pSS. This study aimed to explore potential biomarkers associated with pSS disease progression and analyze the associations between key genes and immune cells.MethodsWe combined our own RNA sequencing data with pSS datasets from the NCBI Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) via bioinformatics analysis. Salivary gland biopsies were collected from 14 pSS patients, 6 non-pSS patients, and 6 controls. Histochemical staining and transmission electron micrographs (TEM) were performed to macroscopically and microscopically characterize morphological features of labial salivary glands in different disease stages. Then, we performed quantitative PCR to validate hub genes. Finally, we analyzed correlations between selected hub genes and immune cells using the CIBERSORT algorithm.ResultsWe identified twenty-eight DEGs that were upregulated in pSS patients compared to healthy controls. These were mainly involved in immune-related pathways and infection-related pathways. According to the morphological features of minor salivary glands, severe interlobular and periductal lymphocytic infiltrates, acinar atrophy and collagen in the interstitium, nuclear shrinkage, and microscopic organelle swelling were observed with pSS disease progression. Hub genes based on above twenty-eight DEGs, including MS4A1, CD19, TCL1A, CCL19, CXCL9, CD3G, and CD3D, were selected as potential biomarkers and verified by RT-PCR. Expression of these genes was correlated with T follicular helper cells, memory B cells and M1 macrophages.ConclusionUsing transcriptome sequencing and bioinformatics analysis combined with our clinical data, we identified seven key genes that have potential value for evaluating pSS severity.

Background: Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease of the exocrine glands characterized by specific pathological features. Previous studies have pointed out that salivary glands from pSS patients express a unique profile of cytokines, adhesion molecules, and chemokines compared to those from healthy controls. However, there is limited evidence supporting the utility of individual markers for different stages of pSS. This study aimed to explore potential biomarkers associated with pSS disease progression and analyze the associations between key genes and immune cells. Methods: We combined our own RNA sequencing data with pSS datasets from the NCBI Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) via bioinformatics analysis. Salivary gland biopsies were collected from 14 pSS patients, 6 non-pSS patients, and 6 controls. Histochemical staining and scanning electron micrographs (SEM) were performed to macroscopically and microscopically characterize morphological features of labial salivary glands in different disease stages. Then, we performed quantitative PCR to validate hub genes. Finally, we analyzed correlations between selected hub genes and immune cells using the CIBERSORT algorithm. Results: We identified twenty-eight DEGs that were upregulated in pSS patients compared to healthy controls. These were mainly involved in immune-related pathways and infection-related pathways. According to the morphological features of minor salivary glands, severe interlobular and periductal lymphocytic infiltrates, acinar atrophy and collagen in the interstitium, nuclear shrinkage, and microscopic organelle swelling were observed with pSS disease progression. Hub genes based on above twenty-eight DEGs, including MS4A1, CD19, TCL1A, CCL19, CXCL9, CD3G, and CD3D, were selected as potential biomarkers and verified by RT-PCR. Expression of these genes was correlated with T follicular helper cells, memory B cells and M1 macrophages. Conclusion: Using transcriptome sequencing and bioinformatics analysis combined with our clinical data, we identified seven key genes that have potential value for evaluating pSS severity. [ABSTRACT FROM AUTHOR]

Animal models of autoimmunity and human genetic association studies indicate that the dysregulation of B-cell receptor (BCR) signaling is an important driver of autoimmunity. We previously showed that in circulating B cells from primary Sjögren’s syndrome (pSS) patients with high systemic disease activity, protein expression of the BCR signaling molecule Bruton’s tyrosine kinase (BTK) was increased and correlated with T-cell infiltration in the target organ. We hypothesized that these alterations could be driven by increased B-cell activating factor (BAFF) levels in pSS. Here, we investigated whether altered BCR signaling was already present at diagnosis and distinguished pSS from non-SS sicca patients. Using (phospho-)flow cytometry, we quantified the phosphorylation of BCR signaling molecules, and investigated BTK and BAFF receptor (BAFFR) expression in circulating B cell subsets in an inception cohort of non-SS sicca and pSS patients, as well as healthy controls (HCs). We found that both BTK protein levels and BCR signaling activity were comparable among groups. Interestingly, BAFFR expression was significantly downregulated in pSS, but not in non-SS sicca patients, compared with HCs, and correlated with pSS-associated alterations in B cell subsets. These data indicate reduced BAFFR expression as a possible sign of early B cell involvement and a diagnostic marker for pSS.

Objective: This paper is aimed at investigating the clinical characteristics of primary Sjogren's syndrome (pSS) with lymphocytic interstitial pneumonia (LIP). Methods: The demographic data, clinical manifestations, laboratory and radiological findings, treatment, and prognosis from 15 cases of pSS-LIP patients were retrospectively analyzed. The data were compared with t test, χ2 test, and Pearson/Spearman correlation analysis. Results: (1) Fifteen cases of patients with pSS-LIP are all females (100%). Compared with pSS with interstitial lung disease(pSS-ILD) patients, the incidence of dry cough, dental caries is higher in pSS-LIP patients. The incidence of shortness of breath, weight loss, and crackles is lower in pSS-LIP patients than that of pSS-ILD patients. (2) Compared with pSS-ILD patients, pSS-LIP patients had higher percentage of patients with ANA, anti-SSA52KD antibody, anti-SSA60KD antibody, and anti-SSB antibody, and the higher concentration of serum globulin. (3) Compared with pSS-ILD patients, the frequency of obstructive ventilation dysfunction is significantly higher and the frequency of diffusion dysfunction is significantly lower in pSS-LIP patients. (4) The most frequent HRCT findings in patients with pSS-LIP is cysts (100%), followed by ground-glass opacities (73.3%), nodular shadow (73.3%) among the pSS-LIP patients. Compared with PSS-ILD patients, the incidence of pulmonary nodule shadow is significantly higher in PSS-LIP patients, while that of grid shadow was significantly lower. (5) Compared with the baseline, the sum of the number, maximum diameter, and diameter of cysts in three levels of pSS-LIP patients showed an increasing trend after treatment. (6) Correlation analysis: The changes of ground-glass opacities were positively correlated with using GC or not, and those were negatively correlated with the dose of GC treatment. Besides, there is a positive correlation between the annual change rate of the maximum diameter of cysts (△Ømax1/t) and the use of CTX; there is a positive correlation between the annual change rate of the total diameter of cysts (△Øsum1/t) and the use of CTX. Conclusion: To the patients of pSS-LIP, female were more common than male, and the onset of LIP was usually more insidious. Hyperglobulinemia and anti-SSA antibody were more prominent in patients with pSS-LIP. Pulmonary function showed the higher rate of obstructive ventilation dysfunction and the lower rate of diffusion dysfunction. The appearance of ground-glass opacities in pSS-LIP patients suggests that the infiltration of inflammatory cells increases, which may cause airway compression, the expansion of terminal bronchioles, and the formation of cysts. The more ground-glass opacities appear earlier, and the more appearance of new cysts later. Therapy with glucocorticoid may be effective on the ground-glass opacity during acute stage, and therapy with cyclophosphamide may be effective on the cysts during chronic stage. The heavier ground-glass opacity is at baseline, the more likely it will recur during maintenance treatment. So follow-up closely is needed. Key Points • It is the first clinical study with more cases of patients with pSS-LIP. • Female and hyperglobulinemia and anti-SSA antibody were more prominent in patients with pSS-LIP. • Pulmonary function showed the higher rate of obstructive ventilation dysfunction and the lower rate of diffusion dysfunction. • Therapy with glucocorticoid may be effective on the ground-glass opacity during acute stage, and therapy with cyclophosphamide may be effective on the cysts during chronic stage. [ABSTRACT FROM AUTHOR]

Objectives Influenza vaccination is effective in preventing infections in most people. This study aimed to assess the changes of immune responses in primary Sjögren's Syndrome (pSS) patients after influenza vaccination and determine the safety of influenza vaccination. Methods A total of 17 patients with pSS and 16 healthy controls (HCs) were included. Peripheral mononuclear cells were analysed by flow cytometry. Vaccine-specific antibodies were determined by ELISA. Clinical features and serological responses were monitored. Results The percentages of T follicular helper cell (Tfh) were significantly elevated in HCs after vaccination (P= 0.0005), while no significant differences in the levels of Tfh in pSS patients were identified (P= 0.1748). The proportions of Th2 cells were significantly decreased after vaccination in both pSS patients and HCs (P< 0.05). In contrast, the percentages of Th1 cells and Th17 cells were significantly increased after vaccination in pSS patients (P< 0.05), while no significant differences in the percentages of Th1 and Th17 cells were identified in HCs (P> 0.05), although a trend towards higher levels of Th1 cells was observed (P= 0.0830). No significant changes in the proportions of memory B cells and plasmablasts were observed after vaccination. Patients with pSS developed higher levels of vaccine-specific IgGs compared with HCs (P= 0.001). No significant changes in disease manifestations and laboratory parameters were observed after vaccination. No increased vaccination related adverse effect was observed in pSS. Conclusion Our findings suggest the feasibility of applying influenza vaccines to patients with pSS, raising awareness for vaccination among the rheumatology community and involved healthcare professionals. [ABSTRACT FROM AUTHOR]

During the development of primary Sjögren's syndrome (pSS), aberrant expression of autoantigen is a hallmark event. To explore the regulation of autoantigen tripartite motif containing 21 (Ro/SSA, TRIM21), microRNA profiling was performed in our previous study. In which, two TRIM21‐targeting microRNAs were identified, namely miR‐1207‐5p and miR‐4695‐3p. To further pursue their roles in the development of pSS, assays were performed with cultured human submandibular gland (HSG) cells, and salivary gland tissues. Results showed that transfection of miR‐1207‐5p or miR‐4695‐3p mimics down‐regulated not only the expression of TRIM21, but also the levels of pro‐apoptotic genes B cell lymphoma 2 associated X (BAX), Caspase 9 (CASP‐9) and Caspase 8 (CASP‐8). This finally led to antiapoptotic phenotypes in HSG cells. Consistent with the antiapoptotic activity, transfection of microRNA inhibitors up‐regulated the expression of TRIM21 and led to a pro‐apoptotic phenotype. These therefore propose miR‐1207‐5p and miR‐4695‐3p as two antiapoptotic microRNAs functioning through apoptosis pathway. Supporting this speculation, assays performed with salivary gland tissues revealed down‐regulation of miR‐1207‐5p and miR‐4695‐3p, as well as up‐regulation of TRIM21 and pro‐apoptotic CASP‐8 gene in pSS samples. Significance of the study: For pSS patients, apoptosis of acinar and ductal epithelial cells has been proposed to be a potential mechanism that impairs the secretion of salivary glands. In our study, two autoantigen‐targeting microRNAs were characterized as antiapoptotic microRNAs functioning through apoptosis pathway, which may be potential targets for the treatment of pSS. [ABSTRACT FROM AUTHOR]

Primary Sjögren’s syndrome (pSS) is a relatively common disease and one of the most common rheumatic diseases of autoimmune and inflammatory origin. It is primarily associated with symptoms of dryness, mainly in the mouth and eyes, but it can also manifest in the internal organs. Epidemiological studies have highlighted that elderly-onset pSS (EOpSS) is common, and it is known that sicca syndrome is a feature often observed in the elderly and can be induced by several factors. However, the presence of autoantibodies in older patients with sicca syndrome can be age-related and does not mean pSS is present. This review article presents the most important elements for making a correct diagnosis of EOpSS and considers clinical and/or laboratory differences between older and younger pSS patients. According to data from the literature, EOpSS is not a distinct subset of disease when compared with younger-onset pSS.

Objective · To investigate the expression level of aquaporin 5 (AQP5) in labial gland, and interleukin-21 (IL-21) and β2-microglobulin (β2-MG) in serum of patients with primary Sjögren's syndrome (pSS) and their association with the activity of the disease. Methods · Thirty-nine patients with pSS were collected and inflammatory indicators such as erythrocyte sedimentation rate (ESR) and IgG were detected. Lip gland biopsy was performed. All specimens were divided into four groups according to Chisholm lip gland pathological classification: Ⅰ, Ⅱ, Ⅲ and Ⅳ. The expression of AQP5 in labial gland was detected by immunohistochemistry and the levels of IL-21 and β2-MG in serum were detected by ELISA. Results · As the number of lymphocytes in labial gland increased, the expression of AQP5 protein decreased. The expression of AQP5 in labial gland was negatively correlated with IL-21, β2-MG, ESR and IgG (r=-0.924, P=0.000; r=-0.366, P=0.022; r=-0.611, P=0.000; r=-0.741, P=0.000). As the number of lymphocytes in labial gland increased, the expression of IL-21 in serum increased, and there was significant difference among four grades. There was no significant difference in serum β2-MG among the groups. Conclusion · The expression of AQP5 in labial gland of patients with pSS is related to lymphocyte infiltration, and AQP5, IL-21 and β2-MG are related to disease activity, which can be used as biological markers for clinical disease evaluation. [ABSTRACT FROM AUTHOR]

Primary Sj€ogren's syndrome (pSS) is a chronic autoimmune disease that is estimated to affect 35 million people worldwide. Hallmarks of the disease are a loss of salivary and lacrimal gland function as well as lymphocytic infiltration, elevated proinflammatory cytokines, and circulating autoantibodies. Patients often experience significant fatigue and a decrease in their quality of life. Approximately 30-50% of pSS patients develop extra-glandular manifestations including malignant lymphoma. Although therapeutic approaches for pSS target both dryness and systemic manifestations, effective treatments are limited. However, new therapies targeting specific immune pathways associated with pSS are being developed. This review describes current and future targeted therapies against pSS. [ABSTRACT FROM AUTHOR]

Butyrophilins are surface receptors belonging to the immunoglobulin superfamily. While several members of the butyrophilin family have been implicated in the development of unconventional T cells, butyrophilin 2a2 (Btn2a2) has been shown to inhibit conventional T cell activation. Here, we demonstrate that in steady state, the primary source of Btn2a2 are thymic epithelial cells (TEC). Absence of Btn2a2 alters thymic T cell maturation and bypasses central tolerance mechanisms. Furthermore, Btn2a2−/− mice develop spontaneous autoimmunity resembling human primary Sjögren's Syndrome (pSS), including formation of tertiary lymphoid structures (TLS) in target organs. Ligation of Btn2a2 on developing thymocytes is associated with reduced TCR signaling and CD5 levels, while absence of Btn2a2 results in increased TCR signaling and CD5 levels. These results define a novel role for Btn2a2 in promoting central tolerance by modulating TCR signaling strength and indicate a potential mechanism of pSS development. • Thymic epithelial cells (TEC) are the primary source of Btn2a2 in steady state. • Absence of Btn2a2 impacts thymic T cell maturation and central tolerance. • Btn2a2 promotes central tolerance by modulating TCR signaling strength. • Btn2a2 absence leads to spontaneous autoimmunity resembling Sjögren's Syndrome. [ABSTRACT FROM AUTHOR]

Background: Primary Sjogren's syndrome (PSS) is a prevalent systemic autoimmune disease. However, the current gold standard diagnostic method is invasive, increasing the difficulty of patient acceptance and then delaying treatment. Therefore, a non-invasive, convenient, and effective diagnostic method is required. Although salivary gland ultrasonography (SGUS) is a good choice, previous studies have not found suitable parameters to diagnose PSS. Salivary gland involvement in patients with PSS leads to changes in gland stiffness and vascularization, so we combined sound touch elastography (STE) and ultra-microangiography (UMA) to demonstrate the diagnostic effectiveness of ultrasonography in PSS., Methods: This prospective study included 27 patients with PSS and 20 healthy controls, with all participants forming a random series. Major salivary glands were examined with UMA and STE. Color pixel percentage (CPP), shear wave velocity (SWV), and Young's modulus values were investigated, and the combination of these parameters was evaluated by logistic regression analysis., Results: For Young's modulus and SWV in the elasticity index, combined evaluation of both parotid glands and submandibular glands yielded an area under the receiver operating characteristic (ROC) curve (AUC) and confidence interval (CI) of 0.819, 0.699-0.938 and 0.801, 0.677-0.925, respectively. The levels of CPP in the parotid glands were significantly elevated (P<0.003) among patients compared to those in the control group, whereas the CPP values in the submandibular glands were not statistically different (P>0.086). We evaluated the elasticity values of the total 4 glands and the CPP of parotid glands together by logistic regression modeling. The ROC curve yielded an AUC of 0.954 (95% CI: specificity 0.849-0.994) which showed the best accuracy, with 92.6% sensitivity and 85.0% specificity., Conclusions: The use of STE and UMA to examine the salivary glands may aid in the diagnosis of PSS, and their combination may be a promising method. This is good news for patients with PSS who are not suitable or unwilling to undergo labial gland biopsy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-711/coif). JP states that he provides Shenzhen Mindray Bio-medical Electronics Co., Ltd. relevant technical consultation only when necessary. The other authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Abstract Primary Sjögren's syndrome (pSS) is a chronic autoimmune rheumatic disease characterized by inflammation of exocrine glands, mainly salivary and lacrimal glands. In addition, pSS may affect multiple other organs resulting in systemic manifestations. Although the precise etiology of pSS remains elusive, pSS is considered to be a multi-factorial disease, where underlying genetic predisposition, environmental factors and epigenetic mechanisms contribute to disease development. Epigenetic mechanisms, such as DNA methylation, histone modifications and non-coding RNAs, may constitute a dynamic link between genome, environment and phenotypic manifestation by their modulating effects on gene expression. A growing body of studies reporting altered epigenetic landscapes in pSS suggests that epigenetic mechanisms play a role in the pathogenesis of pSS, and the reversible nature of epigenetic modifications suggests therapeutic strategies targeting epigenetic dysregulation in pSS. This article reviews our current understanding of epigenetic mechanisms in pSS and discusses implications for novel diagnostic and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Primary Sjogren‘s syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration of exocrine glands. We investigated whether the tolerogenic peptide, hCDR1, that ameliorates lupus manifestations would have beneficial effects on pSS as well. The in vitro effects of hCDR1 on gene expression of pro-inflammatory cytokines and regulatory molecules were tested in peripheral blood mononuclear cells (PBMC) of 16 pSS patients. hCDR1, but not a control peptide, significantly reduced gene expression of IL-1β, TNF-α, MX-1 and BlyS and up-regulated immunosuppressive (TGF-β, FOXP3) molecules in PBMC of pSS patients. hCDR1 did not affect gene expression in patients with rheumatoid arthritis and anti-phospholipid syndrome. Further, hCDR1 up-regulated the expression of Indoleamine 2,3-dioxygenase (IDO) via elevation of TGF-β. IDO inhibition led to a significant decrease in the expression of FOXP3 which is crucial for the induction of T regulatory cells. Thus, hCDR1 is potential candidate for the specific treatment of pSS patients. [ABSTRACT FROM AUTHOR]

Aim The micro RNA-155 (miR-155) is regarded as a central modulator of T-cell responses and could be a potential therapeutic target for certain inflammatory diseases. In our present study we analyzed the expression rate of miR-155 and its functionally linked gene, the suppressor gene of cytokine signaling 1 ( SOCS1) in primary Sjögren's syndrome ( pSS). Method We enrolled 23 pSS patients and 10 healthy individuals in the study. The expression of miR-155 and SOCS1 gene were measured by real-time polymerase chain reaction. Results We observed the over-expression of miR-155 in the peripheral mononuclear cells of patients with pSS. Surprisingly, SOCS1 gene was also over-expressed in pSS patients. Conclusion This unanticipated phenomenon might be a laboratory characteristic of Sjögren's syndrome, and presumably a consequence of the noteworthy difference in the pSS immune system reacting with Epstein-Barr virus. [ABSTRACT FROM AUTHOR]

In non-pSS (Grade II), the duct structure of normal glands is clear, and ductal epithelial cells have full nuclei and are connected with myoepithelial cells by desmosomes. Primary Sjogren's syndrome (pSS), bioinformatics analysis, severity, transcriptome sequencing, potential biomarkers Keywords: primary Sjogren's syndrome (pSS); transcriptome sequencing; potential biomarkers; bioinformatics analysis; severity EN primary Sjogren's syndrome (pSS) transcriptome sequencing potential biomarkers bioinformatics analysis severity 1 2 2 10/01/21 20210929 NES 210929 In the original article, there was a mistake in the legends for B Figures 7 b , B Figure 8 b as published. [Extracted from the article]

Background: Salivary gland enlargement (SGE) is one of the common manifestations in primary Sjögren's syndrome (pSS) patients who are first referred to the hospital of stomatology. Whether the characteristics of the pSS patients with SGE differ from those of the ones without SGE remains unclear. Therefore, this study aimed at investigating the clinical and immunological characteristics related to SGE in pSS, to provide a comprehensive understanding of the clinical phenotype of pSS with SGE., Methods: In this retrospective cross-sectional study, medical records of patients diagnosed with pSS from 2016 to 2021 were evaluated. The included patients were divided into the SGE and non-SGE groups. Patient data including general clinical data, radiographic and B-ultrasound examination data, and immunological data were extracted. Intergroup differences were analyzed using the chi-square test, Fisher's exact test, and non-parametric tests with SPSS 23.0. Binary logistic regression analysis was further performed to determine the factors related to SGE in pSS., Results: Two hundred and three patients with pSS were included, including 126 and 77 patients with and without SGE, respectively. Univariate analysis showed that compared to the non-SGE group, the SGE group was younger, had dry eye symptom for a longer duration, and had a higher proportion of patients with severe conditions on salivary gland radiography (P<0.05). Regarding immunological indicators, the levels of anti-Ro52, anti-SSA (Ro60), and anti-SSB antibodies; immunoglobulin (Ig)G; IgA; and rheumatoid factor (RF) and erythrocyte sedimentation rate (ESR) were significantly higher in the SGE group (P<0.05). Binary logistic regression analysis showed that younger age and high anti-Ro52 levels were independent factors related to SGE in pSS., Conclusions: SGE is highly consistent with increased immunological indicators, reflecting disease activity. pSS patients with SGE were younger than those without. Special attention should be paid to the changes in the anti-Ro52 level since it is an independent factor related to SGE in pSS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-22-289/coif). The authors have no conflicts of interest to declare., (2023 Gland Surgery. All rights reserved.)

It is well known that patients with peripheral neuropathy along with autonomic involvement can also exhibit autonomic hyperactivity. There are rare cases in which these patients developed posterior reversible encephalopathy syndrome (PRES). Patients with primary Sjögren's syndrome (pSS) may be more likely to exhibit autonomic hypofunction rather than autonomic hyperfunction, which is a rare event. In the present work, we report the first known case of PRES as an initial neurological manifestation of pSS. [ABSTRACT FROM AUTHOR]

Objective: This study examined voice, speech, and laryngeal characteristics in primary Sjögren’s syndrome (pSS). Methods: Eleven patients (10 female, 1 male; mean [SD] age = 57 [14] years) from The University of Utah Division of Rheumatology provided connected speech and sustained vowel samples. Analyses included the Multi-Dimensional Voice Profile, the Analysis of Dysphonia in Speech and Voice, and dysphonia severity, speech clarity, and videolaryngostroboscopy ratings. Results: Shimmer, amplitude perturbation quotient, and average fundamental frequency differed significantly from normative values (P < .01). Cepstral Spectral Index of Dysphonia values indicated mild-to-moderate dysphonia in connected speech (mean [SD] = 20.26 [8.36]) and sustained vowels (mean [SD] = 16.91 [11.08]). Ratings of dysphonia severity and speech clarity using 10-cm visual analog scales suggested mild-to-moderate dysphonia in connected speech (mean [SD] = 2.11 [1.72]) and sustained vowels (mean [SD] = 3.13 [2.20]) and mildly reduced speech clarity (mean [SD] = 1.46 [1.36]). Videolaryngostroboscopic ratings indicated mild-to-moderate dryness and mild reductions in overall laryngeal function. Voice Handicap Index scores indicated mild-to-moderate voice symptoms (mean [SD] = 43 [23]). Conclusion: Individuals with pSS may experience dysphonia and articulatory imprecision, typically in the mild-to-moderate range. These findings have implications for diagnostic and referral practices in pSS. [ABSTRACT FROM AUTHOR]

Abstract: Primary Sjogren's syndrome (pSS) is complicated by B-cell lymphoma in 5–10% of patients. Several clinical and serological features are proposed as adverse predictors for such complication and define a high risk pSS phenotype. We aimed to explore whether previously described polymorphisms of the B-cell activating factor (BAFF) could be related to pSS-related lymphomagenesis. Five single nucleotide polymorphisms (SNPs) of the BAFF gene (rs1224141, rs12583006, rs9514828, rs1041569 and the rs9514827) were evaluated in 111 low risk pSS patients (type II), 82 high risk/lymphoma patients (type I) and 137 healthy controls (HC) by PCR-based assays. The classification of pSS patients into types I and II was based on the presence or absence of risk factors or lymphoma development, respectively. Genotype and haplotype analysis was performed for all variants in the pSS groups. Since the rs1041569 SNP was not in Hardy–Weinberg equilibrium in the HC group (p < 0.001), haplotype analysis was performed in the remaining four out of the five SNPs tested when comparisons with HC individuals were performed. The high risk pSS group was characterized by higher frequency of the minor T allele of the rs9514828 BAFF polymorphism compared to HC. Compared to the low risk pSS patients but not the HC, the high risk pSS group exhibited lower frequencies of the AA genotype of the rs12583006 polymorphism as well as the TACAC and TACC haplotypes and higher frequency of the TTTC haplotype. The low risk pSS group exhibited higher frequency of the minor A allele and AA genotype of the rs12583006 variant compared to HC. Both pSS groups were characterized by increased frequency of the haplotype TATT and GTTC and decreased frequency of the TTCT when compared to HC. Taken together, these findings suggest the implication of the host's genetic background in pSS-related lymphomagenesis. The interaction of pSS-related BAFF gene haplotypes together with distinct BAFF genetic variants appears to contribute to this complication. [Copyright &y& Elsevier]

Introduction: Neurological involvements were shown in 20% of patients with Primary Sjogren's Syndrome (pSS). Neurological symptoms may be the first signs of pSS in 57% of the cases. In addition, early diagnosis and treatment of neurological disorders may save or improve the quality of life of these cases. There have been reports about the neurologic manifestations of pSS but little is known about the details of neurologically presented cases. Method: In this study, we described 11 pSS patients who presented with neurological manifestations. Results: Central nervous system (CNS) involvement was recorded in 7 (63.7%) and peripheric nervous system (PNS) involvement in 4 cases (36.4%). Conclusion: Our findings regarding the cases with neurological manifestations leading to the diagnosis of pSS suggest that: 1) The frequency of CNS involvement was higher than that of PNS, and the most frequent clinical pictures of CNS involvement are Multiple Sclerosis (MS)-like illnesses and optic neuritis, 2) Guillain Barre Syndrome (GBS) was the most frequent disease of PNS involvement; 3) Mononeuropathy multiplex (MM) might be the first sign of pSS; 4) Neurologists should consider pSS in the differential diagnosis of cases with MS, optic neuritis, GBS and neuropathies of unknown causes including MM; 5) There is an urgent need of therapeutical guidelines for the cases with neurological involvement associated with pSS. [ABSTRACT FROM AUTHOR]

Highlights: [•] SS is an autoimmune disease with unknown etiology. [•] There is evidence for innate immune activation in early SS disease. [•] Defects in salivary gland development are implicated in disease development. [•] TLR activation in salivary and lacrimal tissue may contribute to SS pathogenesis. [•] Understanding early events in SS will improve diagnosis and therapy for SS patients. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to investigate the possible role of follicular helper T (TFH) cells in the pathogenesis of primary Sjögren's syndrome (pSS) by analyzing immune-competent cells and serological markers with special emphasis on clinical symptoms. We enrolled 50 pSS patients and 16 healthy individuals in the study. Patients had elevated ratio of peripheral TFH cells, however, when dividing patients into two groups defined by the presence of extraglandular manifestations (EGMs), only patients with EGMs differed from controls significantly. Moreover, TFH cell percentages correlated positively with both activated T cell and Tr1 cell values. On the contrary, TFH cell percentages showed negative correlation with both IgM and IgG memory B cell proportions. Elevated TFH percent\ages were observed in the anti-SSA/SSB positive patients, and also in patients with higher IL-12, IL-21 levels and focus score values. Increased TFH cell proportions seem to have an important role in disease development. [Copyright &y& Elsevier]

Renal involvement in primary Sjögren's syndrome (pSS) is not uncommon. Autoimmune tubulointerstitial disorders and distal renal tubular acidosis (dRTA) account for majority of the cases of renal involvement. While dRTA may precede the onset of sicca syndrome in pSS, nephrocalcinosis as a presenting manifestation of pSS is rare. Here, to emphasize the need for initiating investigations for pSS in any patient presenting with nephrocalcinosis due to dRTA, we report a 21-year-old woman presenting with nephrocalcinosis long before pSS was objectively diagnosed. [ABSTRACT FROM AUTHOR]

Abstract: The blood CD4+ CXCR5+ T cells, known as “circulating” Tfh, have been shown to efficiently induce naïve B cells to produce immunoglobulin. They play an important role in certain autoimmune diseases. In the present study, we show for the first time that the frequency of CD4+ CXCR5+ T cells is increased in pSS patients and positively correlated with autoantibodies in the blood. The concentration of Th17-like subsets (CD4+ CXCR5+ CCR6+) in pSS patients was found to be significantly higher than in healthy controls. Functional assays showed that activated Th17-like subtypes in the blood display the key features of Tfh cells, including invariably coexpressed PD-1, ICOS, CD40L and IL-21. Th17 subsets were found to highly express Bcl-6 protein and Th1 and Th2 were not. Bcl-6 is believed to be a master transforming factor for Tfh cell differentiation and facilitate B cell proliferation and somatic hypermutation within the germinal center. These data indicate that Th17 subsets of CD4+ CXCR5+ T cells in the blood may participate in the antibody-related immune responses and that high frequency of CD4+ CXCR5+ CCR6+ Tfh cells in blood may be suitable biomarkers for the evaluation of the active immune stage of pSS patients. It might provide insights into the pathogenesis and perhaps help researchers identify novel therapeutic targets for pSS. [Copyright &y& Elsevier]

A 61-year-old female with a history of vaginal dryness, Raynaud’s phenomenon, xerostomia and xerophthalmia presented with exertional dyspnoea and weakness. Laboratory and instrumental examinations enabled us to make the diagnosis of primary Sjögren’s syndrome, while cardiologic and imaging investigations evidenced isolated pulmonary hypertension and ruled out pulmonary fibrosis. Oral anticoagulant and furosemide therapy induced a partial improvement of exertional dyspnoea and weakness. [ABSTRACT FROM AUTHOR]