BACKGROUND: In vivo confocal microscopy (IVCM) is a vital tool in studying dry eye disease (DED), providing insights into morphological changes at ocular surface unit levels. This review presents the main differences in corneal structure between aqueous-deficient dry eye disease (AD-DED) and normal eyes.
METHODS: A comprehensive search of PubMed, Web of Science, Embase, and MEDLINE databases from January 2000 to December 2023 was conducted. The study selection process, as well as data selection and examination, were independently performed by two members of the review team.
RESULTS: The review reveals a consistent decrease in corneal surface epithelial cell density in AD-DED cases compared to a control group, but conflicting data on basal epithelial cell density. Notably, the abnormal hyperreflectivity of keratocytes in patients with Sjogren\'s syndrome was recorded, and there was a significant keratocyte density in AD-DED subjects compared to evaporative DED and control groups. Studies also found a decrease in sub-basal nerve density, increased tortuosity, and the fragmentation of nerve fibers. Dendritic cell density and dendritic cell dendrites increase in AD-DED patients compared to healthy subjects.
CONCLUSIONS: IVCM is a powerful tool for enhancing our understanding of the pathophysiological mechanisms underlying DED. However, the review underscores the urgent need to standardize the terminology, analysis, and units used for accurate interpretation, a crucial step in advancing our knowledge of DED.

Primary hypokalaemic periodic paralysis during pregnancy has been rarely reported. Four pregnant women with the acute onset of flaccid paralysis presented between January 2018 and December 2021. Focussed history and physical examination helped an appropriate radiological and laboratory investigation plan to be made. All women recovered within 4-7 days of potassium supplementation. Supplemental potassium continued until delivery. A pain management plan with continuous epidural infusion helped in avoiding stress-induced hypokalaemia. None of the women developed an episode of muscle weakness during the intervening period. In conclusion, a focussed history and targeted laboratory investigation are needed to diagnose primary hypokalaemic periodic paralysis. Early administration of oral or intravenous potassium is crucial in improving fetomaternal outcomes.

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BACKGROUND: Primary 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.
METHODS: Through 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.
RESULTS: Via 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.
CONCLUSIONS: Through 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.

(1) Objective: To determine the diagnostic accuracy of major salivary gland ultrasonography (SGUS) in primary Sjogren\'s syndrome (SS), we used the Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system on a large single-centre cohort of patients with sicca syndrome. (2) Method: We retrospectively collected the clinical, imaging and serological data of all the patients referred with a suspicion of SS who underwent SGUS and minor salivary glands biopsy. (3) Results: A total of 132 patients were included. The SGUS scores were correlated between the two sides (p < 0.001). The diagnostic cut-off for SS (AUROC: 0.7408) was 6 for the SGUS-global sum (sensitivity: 32.43%; specificity: 96.84%). The cut-off with the highest specificity for SS diagnosis was 7. In the patients with a final diagnosis of SS, the mean SGUS score was significantly higher (p < 0.001) than that of the non-SS patients (3.73 vs. 1.32 for the SGUS-global sum). A significant correlation was demonstrated between the SGUS scores and final SS diagnosis (p < 0.001), biopsy positivity (p < 0.001), ANA positivity (p = 0.016), Ro-SSA positivity (p = 0.01), and gland fibrosis (p = 0.02). (4) Conclusions: SGUS, using the OMERACT scoring system, has moderate sensitivity and high specificity for the diagnosis of SS. The scoring showed a strong and direct correlation with all the clinical hallmarks of SS diagnosis, such as the positivity of a labial salivary gland biopsy, ANA and Ro-SSA statuses, and salivary gland fibrosis. Because of its high specificity, a SGUS-global score > 6 could be therefore employed for the diagnosis of SS in the case of ANA negativity or the unavailability of a biopsy.

BACKGROUND: Dry eyes and mouth are symptoms of Sjogren syndrome, which can occur on its own and be referred to as primary Sjogren syndrome or in conjunction with other rheumatic diseases like rheumatoid arthritis and be referred to as secondary Sjogren syndrome. Anti-muscarinic type 3 receptors have been linked to neurological issues as well as secretory dysfunction in Sjogren patients. Consequently, the purpose of this study is to determine the serum level of muscarinic acetylcholine receptor subtype 3 (m3AChR)-specific autoantibodies in rheumatoid arthritis (RA) patients and evaluate its relationship to disease activity, functional disability, and to study its role in the development of secondary Sjogren syndrome manifestations in those patients.
METHODS: In this cross-sectional study, 30 RA patients with secondary Sjogren syndrome signs and 30 RA patients without secondary Sjogren syndrome manifestations were included, along with 30 healthy volunteers who were aged, and sex matched as controls. All participants underwent thorough clinical examination, evaluation of disease activity using the DAS28 score, assessment of functional status using the modified health assessment questionnaire (MHAQ), and evaluation of the serum level of (m3AChR) by (ELISA).
RESULTS: When compared to RA patients without secondary Sjogren syndrome and healthy controls (20.09 ± 4.24, 18.36 ± 3.59 ng/ml respectively), the serum level of m3AChR antibodies among 30 RA patients with secondary Sjogren syndrome considerably increased (mean 25.98 ± 4.81 ng/ml).Analysis of the m3AChR\'s (ROC)-curve revealed that the three groups under study differed significantly (P < 0.001), with the AUC (0.806), cutoff (> 22.63ng/ml), sensitivity (73.33%), and specificity (86.67%) all exceeding the threshold. Additionally, there was a significant positive connection between the serum level of m3AChR and the following variables (P < 0.05): DAS scores, MHAQ score, number of tender & swollen joints, and acute phase reactants.
CONCLUSIONS: Autoantibodies against m3AChR may be one of the serum components involved in the pathophysiology of secondary Sjogren syndrome in RA patients, and because of their high sensitivity and specificity, they can be utilized as a diagnostic marker in these individuals.

Hepatitis delta virus (HDV) has been detected in the minor salivary gland (MSG) tissue of Sjögren\'s disease (SjD) patients in the absence of a hepatitis B virus (HBV) coinfection. Previous research has shown that HDV antigen (HDAg) expression can trigger an SjD-like phenotype in vivo, demonstrating a potential cause-and-effect relationship. We hypothesize that if HDV plays a role in the development of SjD, then HDV profiles may be correlated with disease manifestations. This retrospective study characterized HDV in a cohort of 48 SjD MSG samples collected between 2014 and 2021. Analyses of HDAg expression, including cell type and subcellular localization, in situ hybridization of HDV RNA, and comparative analyses with associated SjD and viral hepatitis clinical features, were conducted. HDAg was detected in MSG acinar, ductal, myoepithelial, and adipose cells and localized with the nuclei, cytoplasm, and mitochondria. In situ hybridization detected HDV genomic RNA localization in the MSG nuclei. A significant negative correlation was found between HDAg intensity and focal lymphocytic inflammation and in patients with both anti-SSA/Ro-52 and anti-SSA/Ro-60. In analyzing autoimmune disease comorbidities with SjD, it was found that SjD patients diagnosed with autoimmune thyroiditis and/or hypothyroidism were significantly more represented in the high HDAg intensity group compared to the negative and moderate HDAg intensity groups. No significant associations were detected between MSG-localized HDAg and liver enzymes or an evident HBV coinfection. This study has further confirmed that there is a nonhepatic reservoir for chronic HDV persistence in SjD-affected salivary gland tissue in a third independent SjD patient cohort. In addition, this study describes the unique colocalization of HDAg with mitochondria. The detection of HDV antigen and sequence within SjD-affected salivary gland tissue, and in the absence of an evident current or past HBV coinfection, warrants further investigation.

Xerostomia is the phenomenon of dry mouth and is mostly caused by hypofunction of the salivary glands. This hypofunction can be caused by tumors, head and neck irradiation, hormonal changes, inflammation or autoimmune disease such as Sjögren\'s syndrome. It is associated with a tremendous decrease in health-related quality of life due to impairment of articulation, ingestion and oral immune defenses. Current treatment concepts mainly consist of saliva substitutes and parasympathomimetic drugs, but the outcome of these therapies is deficient. Regenerative medicine is a promising approach for the treatment of compromised tissue. For this purpose, stem cells can be utilized due to their ability to differentiate into various cell types. Dental pulp stem cells are adult stem cells that can be easily harvested from extracted teeth. They can form tissues of all three germ layers and are therefore becoming more and more popular for tissue engineering. Another potential benefit of these cells is their immunomodulatory effect. They suppress proinflammatory pathways of lymphocytes and could therefore probably be used for the treatment of chronic inflammation and autoimmune disease. These attributes make dental pulp stem cells an interesting tool for the regeneration of salivary glands and the treatment of xerostomia. Nevertheless, clinical studies are still missing. This review will highlight the current strategies for using dental pulp stem cells in the regeneration of salivary gland tissue.

Primary Sjögren syndrome (pSS) is a systemic autoimmune inflammatory disease. Up to now, the role of regulatory T cells (Tregs) and their subgroups in pSS is still in controversial. In this study we tried to elucidate the roles of Tregs and its subgroups in pSS. Total 43 pSS patients and 23 health persons as control were enrolled in this study. We grouped the pSS patients according to the anti-SSa/SSb and the EULAR Sjögren\'s syndrome disease activity index (ESSDAI). Among the 43 pSS patients, 14 patients were followed after treatment. The percentage of rTregs (resting Treg cells) among Tregs was increased in the pSS group, and decreased after treatment. In the high disease activity subpopulation (ESSDAI ≥ 5), the percentage of rTregs among Tregs decreased after treatment. On the contrary, the percentage of aTregs (activated Treg cells) increased after treatment. It was in an inverse correlation between the percentage of aTreg and rTreg in pSS patients. The Tregs are co-cultured with responder T cells. Tregs from pSS patients showed poorer proliferation inhibitory function. Our results show that the percentages of Tregs and their subgroups altered in pSS patients. The percentage of aTreg and the percentage of rTreg have an inverse correlation in pSS patients. Compared to the control group, the percentage of rTregs among Tregs was increased in the pSS patients and decreased after the treatment. Our study also showed that The Tregs from pSS patients may have poorer inhibitory functions.

The objective of the study was to compare the efficacy and safety of two concentration of autologous serum (AS) 20% vs 50% in recalcitrant moderate-to-severe dry eye patients.
A double-blind prospective, interventional, and randomized study was done on 44 patients (80 eyes) clinically diagnosed with moderate-to-severe dry eye disease (DED) that was refractory to conventional treatment, and all patients were treated with AS20% or AS50% for 12 weeks. We documented Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), OXFORD corneal staining score (OSS), and Schirmer test (ST) at baseline, 2,4,8, and 12 weeks. These parameters were compared in both groups and between the groups by using Student\'s t-test. The study included 11 males and 33 females.
Out of 80 eyes, 33 eyes had moderate and 47 had severe DED. The age of patients in AS20% was 44.73 ± 14.37 years, and in AS50% was 46.41 ± 14.47 years. The most common etiology associated with DED was secondary Sjogren syndrome. In moderate DED, both the groups showed significant improvement in both subjective and objective parameters. But in severe DED, the AS20% group failed to show any significant improvement objectively, though subjective improvement was present.
In refractory severe DED patients, AS50% is better option for treatment and in moderate DED both concentrations of autologous serum are effective.