Labial Gland Research Articles

Cell death induced by Lepeophtheirus salmonis labial gland protein 3 in salmonid fish leukocytes: A mechanism for disabling host immune responses

The salmon louse (Lepeophtheirus salmonis) is an ectoparasite feeding on mucus, skin, and blood of salmonids. On parasitised fish erosions and, at later lice stages, ulcerations appear at the louse feeding site. In susceptible species like Atlantic salmon (Salmo salar) with a limited rejection of lice, only a mild inflammatory response with minor influx of immune cells is seen at these lesions, as the salmon louse secrete proteins that can dampen immune responses. In a previous study, Lepeophtheirus salmonis labial gland protein 3 (LsLGP3) was suggested to dampen cellular responses, and the present study aimed at increasing our understanding of its mode of action. LsLGP3 was found to be secreted on to the host skin, and both in vivo and in vitro experiments were performed to elucidate its function. Histological analysis of the louse attachment site revealed an epidermal and dermal influx of mainly macrophages and granulocytes after 5 days post infestation. The immune cell influx was deeper in the dermis throughout the louse infestation, and LsLGP3 may be involved in dampening this response. Enriched populations of Atlantic salmon B-cells, T-cells, granulocytes, and monocytes were exposed to recombinant LsLGP3 (recLGP3) in vitro, resulting in a significant decrease in cell viability compared to non-exposed controls. An apoptotic cell morphology with “beads-on-a-string” like protrusions was seen in all leukocyte cell fractions after recLGP3 exposure, but not in erythrocytes or keratocytes. A decreased viability was also detected in pink salmon leucocytes, which was not in leucocytes from non-salmonid species. These functional insights suggest that LsLGP3 specifically induces apoptosis of salmonid leukocytes and is likely a key protein secreted by the lice that disables the Atlantic salmon ability to mount an adequate immune response towards the salmon louse. In vivo LsLGP3 knock down studies indicated that the effect is localised primarily at the lice feeding site, without affecting immune cells that are not situated adjacent to the lice-inflicted lesion. The findings from this study could significantly aid in the development of new immune based anti-salmon louse prophylactic measures and treatments.

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 comprehensive analysis of the tubarial glands.

The tubarial glands (TGs) are a collection of salivary glands (SGs) located within the nasopharynx, proximal to the eustachian tube. Currently, there is no quantitative characterization of the TGs. We investigated the histological architecture of the TGs and compared it with the major and minor SGs for categorization. Tubarial, parotid, submandibular, sublingual, buccal, labial, and lingual glands were excised from human donors (8 male and 3 female). Hematoxylin and eosin-stained tissue sections were analyzed to measure the area of the largest lobule, number of ducts, number of mucinous acini, and mean mucinous acini area. Based on our observation, the TGs' histology resembles the minor SGs, while having some unique characteristics that distinguish them from both major and minor SGs. The area of the largest lobule in the TGs and minor SGs was smaller than the major SGs. TGs have a lower number of ducts than the major and minor SGs. TGs contain densely packed clusters of predominantly mucinous acini surrounded by loose connective tissue resembling minor SGs. This density may explain their previously observed high prostate-specific membrane antigen uptake. In our cohort of donors, sex-based differences were observed in the mean mucinous acini area between male and female TGs, submandibular and sublingual glands. Taken together, our findings suggest the histological characteristics of all SGs are better organized on a spectrum rather than discrete groups (major vs. minor) and provide information to open new avenues for research into the TGs' role in head and neck pathologies and sexual dimorphism of the SGs.

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.

Impact of environmental pollution on ant (Camponotus japonicus) development and labial gland disease

Metallic pollutants can have harmful impacts on ant morphology and physiology. We studied the occurrence of labial gland disease in Camponotus japonicus from two polluted areas (traffic pollution and industrial pollution) and one non-polluted area. We further analyzed the metal levels (Al, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb and Zn) and morphological characteristics (head width, body mass, and other morphological traits) of both diseased and healthy workers. Our results showed that labial gland disease was only present in polluted areas, indicating that pollution stress makes ants more vulnerable to infections. Our research revealed that diseased ants in polluted areas accumulate higher levels of metals in their bodies and have lower dry weight and residual body mass compared to healthy ants in non-polluted environments, negatively impacting their development. We evaluated the importance of these elements and found that Cu has the greatest impact on the health risk of C. japonicus. Our study underscores the significant impact of environmental pollution on ant morphology and physiology and raises concerns about the broader ecological implications.

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.

Evolution of Acquired Perfumes and Endogenous Lipid Secretions in Orchid Bees.

Male orchid bees are unique in the animal kingdom for making perfumes that function as sex pheromone. Males collect volatile chemicals from the environment in the neotropical forests, including floral and non-floral sources, creating complex but species-specific blends. Male orchid bees exhibit several adaptations to facilitate perfume collection and storage. When collecting volatile compounds, males apply lipid substances that they secrete from cephalic labial glands onto the fragrant substrate. These lipids help dissolve and retain the volatiles, similar to the process of 'enfleurage' in the traditional perfume industry. We investigated how the chemical composition of acquired perfume and labial gland secretions varied across the phylogeny of orchid bees, including 65 species in five genera from Central and South America. Perfumes showed rapid evolution as revealed by low overall phylogenetic signal, in agreement with the idea that perfume compounds diverge rapidly and substantially among closely related species due to their role in species recognition. A possible exception were perfumes in the genus Eulaema, clustering closely in chemospace, partly mediated by high proportions of carvone and trans-carvone oxide. Labial gland secretions, in contrast, showed a strong phylogenetic signal at the genus level, with secretions of Eufriesea and Exaerete dominated by fatty acids and Eulaema dominated by saturated acetates of chain lengths 12 to 16 C-atoms. Secretions of the majority of Euglossa were heavily dominated by one unsaturated long chain diacetate, (9Z)-Eicosen-1,20-diyldiacetate. However, we also identified few highly divergent species of Euglossa in four subclades (11 species) that appear to have secondarily replaced the diacetate with other compounds. In comparison with environment-derived perfumes, the evolution of labial gland secretion is much slower, likely constrained by the underlying biochemical pathways, but perhaps influenced by perfume-solvent chemical interactions.

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.

Comparison of epidermal growth factor expression and secretion in human salivary glands

ObjectiveTo investigate the expression and secretion of epidermal growth factor (EGF) in major and minor salivary gland tissues of human subjects and to examine the potential influence of sex and age on EGF expression and secretion. DesignSaliva samples from the oral cavity at rest and after citric acid stimulation, as well as serum samples, were collected from 150 healthy subjects, and the concentrations of EGF were measured with enzyme-linked immunosorbent assay (ELISA) and compared. The expression of EGF mRNA and protein in normal salivary gland tissues was measured by real-time polymerase chain reaction (RT-PCR), Western blot (WB), and immunohistochemistry (IHC). ResultsThe EGF concentration in acid-stimulated saliva was significantly higher than that in resting saliva (P < 0.001), and significantly higher than that in serum (P < 0.001). No sex difference was observed in EGF levels of whole saliva and serum, whereas the EGF levels in saliva and serum were decreased with age (P < 0.001 and P < 0.001, respectively). The EGF concentration and compound secretion rate (CSR) in resting submandibular glands saliva were significantly higher than those in resting parotid glands saliva (P = 0.002 and P < 0.001, respectively). The EGF was expressed in all major and minor salivary glands and ranked in order of submandibular, parotid, sublingual, and labial glands. ConclusionAll salivary glands have the function of secreting EGF, and the submandibular gland is the main source of salivary EGF. Aging is a factor influencing the expression and secretion of EGF.

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.

B cell receptor repertoire analysis in primary Sjogren’s syndrome salivary glands identifies repertoire features associated with clinical activity

BackgroundPrimary Sjogren’s syndrome (pSS) is a complex autoimmune disease featuring damage to salivary and lacrimal glands, with the possibility of manifestations across multiple organs. Antibody-producing B cells have long been appreciated to play a significant role in pSS pathogenesis, with a number of autoreactive antibody species having been identified to be elevated in pSS patients. While several studies have attempted to characterize the BCR repertoires of peripheral blood B cells in pSS patients, much remains unknown about the repertoire characteristics of gland-infiltrating B cells.MethodsThrough paired scRNAseq and scBCRseq, we profiled the BCR repertoires of both infiltrating and circulating B cells in a small cohort of patients. We further utilize receptor reconstruction analyses to further investigate repertoire characteristics in a wider cohort of pSS patients previously profiled through RNAseq.ResultsVia integrated BCR and transcriptome analysis of B cell clones, we generate a trajectory progression pattern for infiltrated memory B cells in pSS. We observe significant differences in BCR repertoires between the peripheral blood and labial gland B cells of pSS patients in terms of relative expansion, isotype usage, and BCR clustering. We further observe significant decreases in IgA2 isotype usage among pSS patient labial and parotid gland B cells these analyses relative to controls as well as a positive correlation between kappa/lambda light chain usage and clinical disease activity.ConclusionsThrough BCR repertoire analysis of pSS patient salivary glands, we identify a number of novel repertoire characteristics that may serve as useful indicators of clinical disease and disease activity. By collecting these BCR repertoires into an accessible database, we hope to also enable comparative analysis of patient repertoires in pSS and potentially other autoimmune disorders.

Defensive glands in Stylotermitidae (Blattodea, Isoptera)

The large abundance of termites is partially achieved by their defensive abilities. Stylotermitidae represented by a single extant genus, Stylotermes, is a member of a termite group Neoisoptera that encompasses 83% of termite species and 94% of termite genera and is characterized by the presence of the frontal gland. Within Neoisoptera, Stylotermitidae represents a species-poor sister lineage of all other groups. We studied the structure of the frontal, labral and labial glands in soldiers and workers of Stylotermes faveolus, and the composition of the frontal gland secretion in S. faveolus and Stylotermes halumicus. We show that the frontal gland is a small active secretory organ in soldiers and workers. It produces a cocktail of monoterpenes in soldiers, and some of these monoterpenes and unidentified proteins in workers. The labral and labial glands are developed similarly to other termite species and contribute to defensive activities (labral in both castes, labial in soldiers) or to the production of digestive enzymes (labial in workers). Our results support the importance of the frontal gland in the evolution of Neoisoptera. Toxic, irritating and detectable monoterpenes play defensive and pheromonal functions and are likely critical novelties contributing to the ecological success of these termites.

Salmon louse labial gland enzymes: implications for host settlement and immune modulation.

Salmon louse (Lepeophtheirus salmonis) is a skin- and blood-feeding ectoparasite, infesting salmonids. While feeding, labial gland proteins from the salmon louse may be deposited on the Atlantic salmon (Salmo salar) skin. Previously characterized labial gland proteins are involved in anti-coagulation and may contribute to inhibiting Atlantic salmon from mounting a sufficient immune response against the ectoparasite. As labial gland proteins seem to be important in the host-parasite interaction, we have, therefore, identified and characterized ten enzymes localized to the labial gland. They are a large group of astacins named L. salmonis labial gland astacin 1-8 (LsLGA 1-8), one serine protease named L. salmonis labial gland serine protease 1 (LsLGSP1), and one apyrase named L. salmonis labial gland apyrase 1 (LsLGAp1). Protein domain predictions showed that LsLGA proteins all have N-terminal ShK domains, which may bind to potassium channels targeting the astacins to its substrate. LsLGA1 and -4 are, in addition, expressed in another gland type, whose secrete also meets the host-parasite interface. This suggests that LsLGA proteins may have an anti-microbial function and may prevent secondary infections in the wounds. LsLGAp1 is predicted to hydrolyze ATP or AMP and is, thereby, suggested to have an immune dampening function. In a knockdown study targeting LsLGSP1, a significant increase in IL-8 and MMP13 at the skin infestation site was seen under LsLGSP1 knockdown salmon louse compared to the control, suggesting that LsLGSP1 may have an anti-inflammatory effect. Moreover, most of the identified labial gland proteins are expressed in mature copepodids prior to host settlement, are not regulated by starvation, and are expressed at similar or higher levels in lice infesting the salmon louse-resistant pink salmon (Oncorhynchus gorbuscha). This study, thereby, emphasizes the importance of labial gland proteins for host settlement and their immune dampening function. This work can further contribute to anti-salmon louse treatment such as vaccine development, functional feed, or gene-edited salmon louse-resistant Atlantic salmon.

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.

Anticholinergic burden of medications is associated with dry mouth and reflected in minor labial gland secretion

ObjectiveMedications with anticholinergic potential inhibit saliva secretion. Polypharmacy potentiates anticholinergic burden, causing dry mouth symptoms and chronic deterioration of oral health. Patients of any age can be affected by anticholinergic medication-triggered hyposalivation (the objective measure of dry mouth); therefore, seeking predictions of hyposalivation to screen dry mouth is needed. DesignIn our prospective, cross-sectional clinical study, 55 middle-aged adult patients participated. We examined whether the anticholinergic burden calculated from anticholinergic medications (anticholinergic drug score; ADS) and blood serum anticholinergic activity (SAA; the gold standard measure of anticholinergic burden) is associated with hyposalivation. As no prior studies measured minor salivary glands regarding the quantifiable anticholinergic burden, we assessed hyposalivation by the minor saliva flow (MSF) and unstimulated whole saliva (UWS) secretion. ResultsOur data showed a negative linear relationship between SAA and UWS (p < 0.05); when SAA increases by one pmol/ml unit, the saliva flow decreases by 0.058 ml/min. MSF showed a linear correlation (p < 0.005) with UWS. In a multivariate logistic regression model (including age, gender, race, smoking status, xerostomia severity, ADS, and BMI), we identified SAA and age as predictors of hyposalivation (p < 0.05). ConclusionsWe provide evidence for the significant relationship between measurable anticholinergic burden and saliva flow. The correlation between UWS and MSF suggests that both saliva flow rate measurement methods could reflect anticholinergics-induced changes in salivary health.

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.