Labial Gland Biopsy Research Articles

A deep learning based assisted analysis approach for Sjogren's syndrome pathology images.

Diagnosing Sjogren's syndrome requires considerable time and effort from physicians, primarily because it necessitates rigorously establishing the presence lymphatic infiltration in the pathological tissue of the labial gland. The aim of this study is to use deep learning techniques to overcome these limitations and improve diagnostic accuracy and efficiency in pathology. We develop an auxiliary diagnostic system for Sjogren's syndrome. The system incorporates the state-of-the-art object detection neural network, YOLOv8, and enables the precise identification and flagging of suspicious lesions. We design the multi-dimensional attention module and S-MPDIoU loss function to improve the detection performance of YOLOv8. By extracting features from multiple dimensions of the feature map, the utilization of the multi-dimensional attention mechanism enhances the feature interaction across disparate positions, enabling the network to proficiently learn and retain salient cell features. S-MPDIoU introduces an angle penalty term that efficiently minimizes the diagonal distance between predicted and ground truth boxes. Additionally, it incorporates a flexible scale factor tailored to different size feature maps, which balances the issue of sudden gradient decrease during high overlap, thereby accelerating the overall convergence rate. To verify the effectiveness of our methods, we create a dataset of lymphocytes using labial gland biopsy pathology images collected from YanTaiShan hospital and trained the model with this dataset. The proposed model is assessed using standard metrics like precision, recall, mAP. The improved model achieves an increase in recall by 9.1%, mAP.5 by 3.2%, and mAP.95 by 2%. The study demonstrated deep learning's potential to analysis pathology images, offering a reference framework for the application of deep learning technology in the medical domain.

Histological differences related to autophagy in the minor salivary gland between primary and secondary types of Sjögren’s syndrome

Some forms of Sjögren’s syndrome (SS) follow a clinical course accompanied by systemic symptoms caused by lymphocyte infiltration and proliferation in the liver, kidneys, and other organs. To better understand the clinical outcomes of SS, here we used minor salivary gland tissues from patients and examine their molecular, biological, and pathological characteristics. A retrospective study was performed, combining clinical data and formalin-fixed paraffin-embedded (FFPE) samples from female patients over 60 years of age who underwent biopsies at Okayama University Hospital. We employed direct digital RNA counting with nCounter® and multiplex immunofluorescence analysis with a PhenoCycler™ on the labial gland biopsies. We compared FFPE samples from SS patients who presented with other connective tissue diseases (secondary SS) with those from stable SS patients with symptoms restricted to the exocrine glands (primary SS). Secondary SS tissues showed enhanced epithelial damage and lymphocytic infiltration accompanied by elevated expression of autophagy marker genes in the immune cells of the labial glands. The close intercellular distance between helper T cells and B cells positive for autophagy-associated molecules suggests accelerated autophagy in these lymphocytes and potential B cell activation by helper T cells. These findings indicate that examination of FFPE samples from labial gland biopsies can be an effective tool for evaluating molecular histological differences between secondary and primary SS through multiplexed analysis of gene expression and tissue imaging.

A graph-learning based model for automatic diagnosis of Sjögren’s syndrome on digital pathological images: a multicentre cohort study

BackgroundSjögren’s Syndrome (SS) is a rare chronic autoimmune disorder primarily affecting adult females, characterized by chronic inflammation and salivary and lacrimal gland dysfunction. It is often associated with systemic lupus erythematosus, rheumatoid arthritis and kidney disease, which can lead to increased mortality. Early diagnosis is critical, but traditional methods for diagnosing SS, mainly through histopathological evaluation of salivary gland tissue, have limitations.MethodsThe study used 100 labial gland biopsy, creating whole-slide images (WSIs) for analysis. The proposed model, named Cell-tissue-graph-based pathological image analysis model (CTG-PAM) and based on graph theory, characterizes single-cell feature, cell-cell feature, and cell-tissue feature. Building upon these features, CTG-PAM achieves cellular-level classification, enabling lymphocyte recognition. Furthermore, it leverages connected component analysis techniques in the cell graph structure to perform SS diagnosis based on lymphocyte counts.FindingsCTG-PAM outperforms traditional deep learning methods in diagnosing SS. Its area under the receiver operating characteristic curve (AUC) is 1.0 for the internal validation dataset and 0.8035 for the external test dataset. This indicates high accuracy. The sensitivity of CTG-PAM for the external dataset is 98.21%, while the accuracy is 93.75%. In comparison, the sensitivity and accuracy for traditional deep learning methods (ResNet-50) are lower. The study also shows that CTG-PAM’s diagnostic accuracy is closer to skilled pathologists compared to beginners.InterpretationOur findings indicate that CTG-PAM is a reliable method for diagnosing SS. Additionally, CTG-PAM shows promise in enhancing the prognosis of SS patients and holds significant potential for the differential diagnosis of both non-neoplastic and neoplastic diseases. The AI model potentially extends its application to diagnosing immune cells in tumor microenvironments.

Questionnaire survey of the application of four objective indicators necessary for standardized diagnosis of Sjögren's syndrome

Objective: To investigate the current status and challenges of carrying out the four objective indicators which are necessary for the Sjögren's syndrome (SS) diagnosis in hospitals all over China. Methods: A questionnaire survey was conducted online by Questionstar from May to July 2023 among rheumatologists nationwide, to investigate whether unstimulated salivary flow (UWSF), Van Bijsterveld score (VBS), Schirmer test and labial gland focus score (FS) are carried out in their hospitals and the challenges that hinder their development. A cohort of patients with established SS was enrolled to verify the importance of the four objective indicators in diagnosing SS. Statistical analyses were performed using the chi-square test. Results: The questionnaire was completed by rheumatologists from 660 hospitals in 225 cities of 32 provinces, autonomous regions and municipalities all over China (one doctor from each hospital completed the questionnaire), of which 548 (83.0%) were tertiary care hospitals. The rate of carrying out the objective indicators in 660 hospitals was low: UWSF (290/660, 43.9%), FS (497/660, 75.3%) and VBS (393/660, 59.5%). The percentage of hospitals who consider it difficult to carry out UWSF, VBS, minor labial gland biopsy and Schirmer test was 92.6%(611/660), 69.4%(458/660), 59.8%(395/660) and 58.6%(387/660), respectively. All four objective indicators mentioned above could be carried out in only 139 (21.1%) hospitals. In 521 hospitals in which less than four objective indicators could be carried out, 23.2% (121/521) of rheumatologists selected clinical experience to diagnose SS. A total of 180 patients with SS diagnosed by perfecting all objective indices and meeting the 2016 the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria were included, 173 females (96%), aged (46.6±13.6) years, with the missed diagnosis rate was 17.8% (32/180) assuming their labial FS was unavailable. In 166 patients with established SS who met the classic 2002 AECG criteria, 160 females (96%), aged (47.0±13.6) years, the missed diagnosis rate was 52.4% (87/166) assuming their labial FS was unavailable; or 10.8% (18/166) assuming their UWSF was unavailable. SS diagnosis couldn't be estimated according to 2002 AECG criteria, assuming both labial FS and UWSF were unavailable in 156 (94.0%) patients with positive anti-SSA/Ro; or assuming either labial FS or UWSF was unavailable in 10 (6.0%) patients with negative anti-SSA/Ro. Conclusion: The application rates of four objective indicators necessary for SS diagnosis are low, the rate of carrying out labial gland biopsy should be increased, and the labial FS reports and UWSF test should be standardized.

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.

The Value of Labial Gland Biopsies as a Diagnostic Test for Sjögren’s Syndrome

PurposeThere are a number of diagnostic criteria that can be used to support a diagnosis of Sjögren’s syndrome (SS), a chronic autoimmune condition often characterised by xerostomia and xerophthalmia. Of the available investigations, the most invasive is the labial gland biopsy (LGB) for histopathology, which is associated with a risk of long-term altered sensation to the lip. A positive histological diagnosis is currently considered to be one of the most objective criteria, however there is debate about the interobserver agreement between pathologists, as well as the sensitivity and specificity of this test. We aim to determine if the diagnostic value of the LGB is significant enough to warrant the surgical procedure and its associated risks.MethodsThis study involved assessing the degree of agreement between members of a pathology team for a cohort of 50 LGBs taken for the purpose of confirming or excluding SS. The Tarpley system was used, which involves the allocation of a ‘focus score’. Additionally, the histological diagnoses were compared to the relevant serological findings where available.ResultsAll cases within the cohort had adequate tissue for assessment. 84% agreement (Cohen’s Kappa = 0.585) was seen between the current team’s consensus and the original reporting pathologist on whether the appearance was supportive of SS. However, only 58% agreement was seen for focus scores (Weighted Kappa = 0.496). The agreement between the serology result and whether the histology was supportive of SS was 79% (Cohen’s Kappa = 0.493).ConclusionThe findings raise the possibility that undue emphasis is placed on the value of a histological SS diagnosis. The current system for assessing and grading these biopsies is ambiguous in nature, with a low threshold considered indicative of SS. Due to the risk of complications associated with a LGB, alternative minimally invasive investigations should always be considered. The histological findings in isolation, particularly when a low focus score is seen, may not be predictive of a diagnosis of SS.

Histopathological comparison of Sjögren-related features between paired labial and parotid salivary gland biopsies of sicca patients.

To compare focus score and other histopathological features between paired labial and parotid salivary gland biopsies in a diagnostic cohort of suspected Sjögren's disease (SjD) patients. Labial and parotid salivary gland biopsies were simultaneously obtained from patients with sicca complaints, suspected of having SjD. Biopsies were formalin fixed and paraffin embedded. Sections were stained with haematoxylin & eosin, and for CD3, CD20, CD45, cytokeratin, CD21, Bcl6, activation-induced deaminase (AID) and IgA/IgG. Focus score and other histopathological features characteristic for SjD were analysed. Based on the expert opinion of three experienced rheumatologists, 36 patients were diagnosed as SjD and 63 as non-SjD sicca patients. When taking all patients together, absolute agreement of various histopathological features between labial and parotid biopsies was high and varied between 80% (focus score) and 93% [(pre-)lymphoepithelial lesions (LELs)]. More labial gland biopsies had a focus score ≥1 compared with their parotid counterpart. Accordingly, the area of infiltrate was larger in labial gland biopsies. When considering only SjD patients, labial glands contained significantly fewer B-lymphocytes and germinal centres/mm2, and less severe LELs compared with parotid glands. Labial and parotid glands from SjD patients contain similar histopathological key features, and thus both glands can be used for diagnosis and classification of SjD. However, parotid salivary glands reveal more evident B-lymphocyte-related features, while labial glands exhibit more inflammation, which may be partially unrelated to SjD.

Increased Diagnostic Accuracy of the Labial Gland Biopsy in Primary Sjögren Syndrome When Multiple Histopathological Features Are Included.

The aim of this study was to evaluate the diagnostic accuracy of the labial salivary gland biopsy based on multiple histopathological features in patients with suspected primary Sjögren syndrome (pSS). Patients from a diagnostic sicca cohort with clinically suspected pSS who underwent a labial gland biopsy were included. Patients were categorized as having pSS or non-Sjögren syndrome sicca (non-SS sicca) based on vignettes scored by an expert panel. Labial gland biopsies were analyzed for the presence of four histopathological features: focus score (FS) ≥1, prelymphoepithelial and lymphoepithelial lesions, immunoglobulin G plasma cell shift, and germinal centers. Sensitivity and specificity of histologic features were calculated, and the optimal cutoff value for the number of histopathological features needed to diagnose pSS was determined with receiver operating curve analysis. A total of 38 patients were categorized as having pSS and 65 as having non-SS sicca. In labial gland biopsies of patients with pSS, the prevalence of FS ≥1 was 82%, followed by 68% for pre-lymphoepithelial and lymphoepithelial lesions, 63% for plasma cell shift, and 24% for germinal centers. Although FS ≥1 showed the highest sensitivity for patients with pSS (82%), specificity was higher for the other three features (98%-100%). The presence of two or more (of four) histopathological features had almost comparable sensitivity to FS alone, but specificity increased with 12% to 100%. For fulfillment of American College of Rheumatology/EULAR criteria, specificity increased from 84% to 95% when an abnormal biopsy was defined by the presence of two or more histopathological features instead of FS ≥1 only. The diagnostic accuracy of the labial gland biopsy increases when other histopathological features besides FS are taken into account, by reducing the number of false-positive biopsies.

Coexistent Sjogren’s syndrome and Birt-Hogg-Dube´ syndrome: a case report

We report a rare case of Sjogren’s syndrome complicated with Birt-Hogg-Dubé syndrome (BHDS) not previously mentioned in the literature. Further, there is insufficient evidence linking the two diseases. Here, we review existing diagnostic algorithms for diagnosing diffuse cystic lung disease and provide new insights. The patient initially complained of thirst and dry eyes for ten years, and gradually developed shortness of breath. After admission, physical examination showed five missing teeth, decreased respiratory sounds in both lower lungs, and Velcro rales. Computed tomography showed multiple thin-walled cystic lesions in both lungs. Initial xerophthalmia and labial gland biopsy seemed to reveal a pulmonary cystic change associated with Sjogren’s syndrome. Before discharge, a rash suspected to indicate a fibrofollicular tumor in the neck was observed, and then FLCN variant has been found. The challenges how to clarify the diagnosis of DCLD causes are discussed.

Utility of labial salivary gland biopsy in the histological diagnosis of neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) poses a diagnostic challenge because of its diverse clinical manifestations. Detection of intranuclear inclusions remains the primary diagnostic criterion for NIID. Skin biopsies have traditionally been used, but concerns exist regarding postoperative complications and scarring. We sought to investigate the diagnostic utility of labial salivary gland biopsy, a less invasive alternative. This study included a total of 19 patients and 11 asymptomatic carriers who underwent labial gland biopsies, while 10 patients opted for skin biopsies. All these individuals were confirmed to have pathogenic GGC repeat expansions in the NOTCH2NLC gene. The control group comprised 20 individuals matched for age and sex, all with nonpathogenic GGC repeat expansions, and their labial gland tissue was sourced from oral surgery specimens. Labial gland biopsies proved to be a highly effective diagnostic method in detecting eosinophilic intranuclear inclusions in NIID patients. The inclusions showed positive staining for p62 and ubiquitin, confirming their pathological significance. The presence of uN2CpolyG protein in the labial gland tissue further supported the diagnosis. Importantly, all patients who underwent lip gland biopsy experienced fast wound healing without any noticeable scarring. In contrast, skin biopsies led to varying degrees of scarring and one instance of a localized infection. Labial salivary gland biopsy emerged as a minimally invasive, efficient diagnostic method for NIID, with rapid healing and excellent sensitivity.

Combination of ultra-micro angiography and sound touch elastography for diagnosis of primary Sjögren's syndrome: a diagnostic test.

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. 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. 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. 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.

Identification of key genes in salivary gland in Sjögren's syndrome complicated with Hashimoto thyroiditis: Common pathogenesis and potential diagnostic markers.

The coexistence of Sjögren's syndrome (SS) and Hashimoto thyroiditis (HT) has been confirmed, but the common mechanism of its co-occurrence remains unknown. This study aims to further explore the underlying mechanism and biomarkers for the co-occurrence of SS and HT. The Gene Expression Omnibus databases were used to obtain gene expression profiles for SS (GSE127952 and GSE23117) and HT (GSE29315 and GSE138198). Following identifying SS and HT's shared differentially expressed genes, functional annotation, protein-protein interaction network creation, and module assembly were performed to discover hub genes. H&E staining and immunohistochemistry were performed to validate the expression of the hub genes in salivary glands. Finally, the receiver operating characteristic (ROC) curve was utilized to assess the discrimination of the hub genes as biomarkers in predicting SS, this study applied CIBERSORTx to analyze the immune infiltration in SS and HT in addition. A total of 48 common differentially expressed genes (48 upregulated genes and 0 downregulated genes) were chosen for further investigation. We analyzed the expression and function of PTPRC, CD69, IKZF1, and lymphocyte cytosolic protein 2 via H&E, immunohistochemistry, and ROC analysis. The 4 hub genes were mainly enriched in the T-cell receptor signaling pathway. We then evaluated and verified the diagnosis value of 4 hub genes in clinical minor labial gland biopsy of SS with HT, SS without HT, and non-SS. ROC analysis revealed that the 4 hub genes had a strong diagnostic value. Our study showed the common pathogenesis of SS and HT. These hub genes and diagnostic models may put forward some new insights for diagnosing and treating SS complicated with HT.

The plasma exosomes from patients with primary Sjögren's syndrome contain epithelial cell-derived proteins involved in ferroptosis.

Primary Sjögren's syndrome (pSS) is an autoimmune disease represented by exocrine gland epithelial cell lesions. However, the mechanism underlying these lesions remains unclear. This study analyzed the plasma exosomes of pSS patients using proteomics and revealed the presence of 24 differentially expressed proteins (DEPs) involved in the primary biological processes and signaling pathways related to ferroptosis. The DEPs enriched in the ferroptosis-related items were represented by downregulated ceruloplasmin (CP) and transferrin (TF). CC analysis of GO enrichment showed that CP and TF were localized at the apical plasma membrane, which is currently found only in epithelial cells. PPI analysis indicated that these exosomal DEPs formed a clustering network containing CP and TF. Among them, C5, C9, Haptoglobin (HP), and SERPING1 interacted directly with CP and TF. Notably, the expression of these proteins significantly decreased in both the pSS and secondary Sjögren's syndrome (sSS) plasma exosomes but not in non-autoimmune sicca syndrome (nSS). In addition, their expression levels were significantly different in the exosomes and plasma. More importantly, the plasma and salivary exosomes of pSS patients contain higher levels of exocrine gland epithelial autoantigens SSA and SSB than those of healthy controls, and epithelial cells with positive labial glands biopsy (LGB) were more susceptible to ferroptosis than those with negative LGB. The results indicated that ferroptosis may be closely related to SS epithelial cell lesions. KEY MESSAGES: • pSS plasma exosomes contain epithelial cell-derived proteins involved in ferroptosis. • Complement C5 and C9 may be new molecules involved in ferroptosis and play a crucial role in pSS epithelial cell pathology. • The serum exosomes from pSS patients, not nSS patients, contain ferroptosis-related proteins. • The changes in the ferroptosis-related protein content in the exosomes can better reflect the state of the epithelial cell lesions than those in the plasma.

Non-invasive diagnosis of primary Sjögren's syndrome using ultrasonography and transcriptome biomarkers

Diagnosing primary Sjögren's syndrome (pSS) is difficult due to clinical heterogeneity and the absence of non-invasive specific biomarkers. To develop non-invasive pSS diagnosis methods that integrate classic clinical indexes, major salivary gland ultrasonography (SGUS), and gene expression profiles shared by labial gland and peripheral blood, we conducted a study on a cohort of 358 subjects. We identified differentially expressed genes (DEGs) in glands and blood that were enriched in defense response to virus and type I interferon production pathways. Four upregulated DEGs common in glands and blood were identified as hub genes based on the protein-protein interaction networks. A random forest model was trained using features, including SGUS, anti-SSA/Ro60, keratoconjunctivitis sicca tests, and gene expression levels of MX1 and RSAD2. The model achieved comparable pSS diagnosis accuracy to the golden standard method based on labial gland biopsy. Our findings implicate this novel model as a promising diagnosis technique of pSS.

Clinical and laboratory features of childhood-onset primary Sjögren's syndrome: A retrospective study from China.

The initial presentations of childhood-onset primary Sjögren's syndrome (C-pSS) vary, making diagnosis challenging. We aimed to improve the diagnosis and evaluation of C-pSS by summarizing its clinical and laboratory features. A total of 49 patients with C-pSS between July 2015 and August 2022 in the Department of Rheumatology and Immunology of Shanghai Children's Medical Centre were enrolled in this study. Their clinical manifestations and laboratory examinations of these patients were compared based on the presence or absence of thrombocytopenia and parotitis and whether the immunological markers, including anti-nuclear antibodies (ANA), rheumatoid factor (RF), anti-Ro52/SSA antibodies (anti-SSA/Ro52), anti-Ro60/SSA antibodies (anti-SSA/Ro60), and anti-Ro/SSB antibodies (anti-SSB), were positive. The mean age at C-pSS diagnosis was 10.34 ± 3.45years, and the ratio of boys to girls was 1:6. In the thrombocytopenia group, parotitis (P = 0.044), organ involvement except for hematology (P = 0.002), positive anti-SSB (P = 0.004), and positive RF (P = 0.001) were less frequently observed. Complement C4 (P = 0.038) and white blood cells (P = 0.002) levels decreased and increased significantly, respectively. Anti-SSB (P = 0.010) and RF (P = 0.004) positivity were independent potential protective factors against thrombocytopenia in patients with C-pSS. In the parotitis group, higher ANA titers (P = 0.027), higher focus scores on labial gland biopsy (P = 0.024), and positive RF (P = 0.001), anti-SSA/Ro60 (P = 0.003), and anti-SSB (P = 0.001) were observed more frequently. Furthermore, positive anti-SSB (P = 0.012) and positive RF (P = 0.028) were independent risk factors for parotitis in patients with C-pSS. The hemoglobin level was significantly lower in patients with positive anti-SSA/Ro52 and positive anti-SSA/Ro60 results (P = 0.022 and P = 0.029, respectively), while immunoglobulin G level was significantly higher in patients in the same group (P = 0.048 and P = 0.007, respectively). Positive anti-SSB and positive RF values may be independent potential protective factors of thrombocytopenia in patients with C-pSS. In contrast, positive anti-SSB and positive RF were independent risk factors of parotitis in patients with C-pSS. More studies are needed to reveal the diagnostic role and pathogenic mechanism of immunological markers in C-pSS.

Primary Sjögren’s syndrome-related Choroiditis in a Newly Diagnosed Older Adult

ABSTRACT Purpose To report a case of secondary bilateral choroiditis in a patient with primary Sjögren’s syndrome(pSS). Study Design Case report. Results A 69-year-old woman visited our hospital for consultation due to decreased visual acuity in both eyes for 1 month. At the first visit, best corrected visual acuity (BCVA) was 0.2 and 0.3 in her right and left eyes, respectively. Intraocular pressure values were 15 mmHg and 16 mmHg in her right and left eyes, respectively. Examination revealed edema of the eyelids and conjunctiva,and corneal fluorescence staining was positive. No inflammation in the anterior chamber or vitreous opacities were observed. Bilateral multiple retinal detachments were observed on the posterior fundus, and optical coherence tomography revealed bilateral multiple areas of retinal neuroepithelial detachment, choroidal thickening, and choroidal folds. No abnormal fluorescence leakage was observed on fundus fluorescein angiography or indocyanine green angiography. In addition, systematic manifestations included recurrent bilateral parotid gland enlargement. Labial gland biopsy revealed dilated glandular ducts, scattered interstitial glands, and lymphocytic foci. Salivary gland scintigraphy revealed severe impairment of glandular excretory function. Moreover, blood tests for anti-Ro/SSA and anti-La/SSBantibodies were positive. The patient was diagnosed with primary Sjögren’s syndrome. After 2 months treatment with oral prednisolone acetate combined with hydroxychloroquine, her BCVAimproved to 0.8 and 1.0 in the right and left eyes, respectively. The fundus also recovered to normal, and no recurrence was observed during the 1-year follow-up period. Conclusions The current case highlights that pSS, which usually manifests with dry eye and keratoconjunctivitis, may manifest with chronic choroiditis in both eyes as well. Based on our experience with this case, patients with clinically suspected bilateral choroiditis should be evaluated for pSS.

Corneal subbasal nerve analysis in patients with primary Sjogren's syndrome: a novel objective grading method and clinical correlations.

To investigate corneal sub-basal nerve morphology changes in primary Sjogren's syndrome (SS) dry eye (SSDE) patients and determine the association with disease severity at microstructural level. Twenty-eight eyes of 17 SSDE and 82 eyes of 47 age- and sex-matched non-SS dry eye (NSSDE) patients were included. The Ocular Surface Disease Index questionnaire (OSDI), Schirmer's test (ST), tear meniscus height (TMH), non-invasive breakup time (NIBUT), meibomian gland (MG) morphology, and ocular staining score (OSS) were assessed. In vivo confocal microscopy was performed to observe corneal sub-basal nerve morphology (length, reflectivity, width, and tortuosity). Associations between clinical features and nerve parameters were analysed. SSDE patients more frequently had increased nerve reflectivity (151.12 ± 17.07 vs. 139.37 ± 14.31 grey value), width (4.45 ± 0.87 vs. 3.92 ± 0.81μm), tortuosity (132.90 ± 8.04 vs. 129.50 ± 7.33 degree), and higher reflectivity, width, and total nerve grades than NSSDE individuals (all P < 0.05). Significant associations were found between nerve reflectivity/width and anti-SSA [OR = 1.139 (1.013-1.281)/1.802 (1.013-4.465)]/labial gland biopsy [OR = 1.046 (1.002-1.161)/1.616 (1.020-3.243)]. Higher nerve width was associated with increased OSDI [β = 0.284 (0.187-0.455)], MG score [β = 0.185 (0.109-0.300)] and OSS [β = 0.163 (0.020-0.345)], but decreased NIBUT [β = - 0.247 (- 0.548 ~ - 0.154)]. Higher nerve total grade was associated with increased OSDI [β = 0.418 (0.157-0.793)] and OSS [β = 0.287 (0.027-0.547)], but decreased ST [β = - 0.410 (-0.857 ~ - 0.138)]. Corneal nerve morphology changes associated with clinical features in SS patients. These changes may facilitate severity evaluation and management of the disease.

Study of clinical factors, focus score, lymphocyte type and NF-κB pathway in Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease that occurs predominantly in middle-aged and older women. Although focus score (FS) and lesion grade are determined at pathological diagnosis, few reports have examined whether these results reflect clinical symptoms. In this study, we examined and compared the results of comprehensive immunohistochemical staining of lymphocytes and NF-κB pathway in labial gland biopsies, clinical test data, and radionuclide imaging findings. One hundred labial gland biopsy specimens obtained from 20 female patients with primary SS (5 specimens per patient) were studied. Hematoxylin-eosin-stained specimens were reviewed and FS were calculated. Immunohistochemical staining of CD4, CD8, CD20, CD25, Foxp3, NF-κB, TNFAIP3 and IκBα was performed, and the results were compared with anti-SS-A/Ro (SS-A), anti-SS-B/La (SS-B) and antinuclear antibodies (ANA), and salivary gland scintigraphy findings. FS were significantly higher in the SS-A-, SS-B- and ANA-positive groups than in the respective -negative groups (p < 0.05). Of eight SS-A-positive and SS-B-negative cases, mean FS was 1.9 (seven cases: FS ≥ 1.0) and six cases were ANA-positive. In four SS-A-positive and SS-B-positive cases, mean FS was 3.2 (all cases: FS ≥ 1.0) and all cases were ANA-positive. In immunohistochemical staining, CD4-positive T cells tended to be more abundant than CD8-positive T cells. Small numbers of Foxp3-positive cells were found in all cases. NF-κB, TNFAIP3 and IκBα were positive in the acini, ductal epithelium, and lymphocytes in all cases. The above findings indicated a relationship between FS and clinical test data, and the association of NF-κB pathway with the pathophysiology of primary SS.

Blister as A Cutaneous Manifestation of Sjogren’s Syndrome Determines IL-6 Antibody to Be A Potential Treatment: A Case Report

A 64 years old female was admitted to hospital due to having repeated blister on skin. Her Dsg1, Dsg3, Bp180, Bp230, VII collagen antibodies were all negative while her ENA-SSA and anti-CCP were positive. Labial glands biopsy revealed that lymphocytes immersed around the glands and a diagnose of Sjögren’s syndrome (SS) was made. Skin biopsy indicated subcorneal pustular with neutrophils immersed and direct immune fluorescence as well as blood and blister fluid culture were negative. Additionally, the patient showed a high expression of IL-6 (18371.09pg/mL) in peripheral blood and blister fluid (19997.89pg/mL).

Utility of the labial gland biopsy for the diagnosis of AL amyloidosis

Utility of the labial gland biopsy for the diagnosis of AL amyloidosis