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Annals of Medicine and Surgery (2012) Jul 2023The incidence of neurological injury in primary Sjogren's syndrome varies between 2.5 and 60%. The authors aimed to evaluate its prevalence and characteristics in...
UNLABELLED
The incidence of neurological injury in primary Sjogren's syndrome varies between 2.5 and 60%. The authors aimed to evaluate its prevalence and characteristics in patients with primary Sjogren's syndrome in a sample of the Syrian population.
PATIENTS AND METHODS
Forty-eight patients with primary Sjogren's syndrome, attending outpatient clinics at Damascus Hospital between January 2020 and January 2022 in this cross-sectional study at the outpatient clinics, were interviewed and examined, and the necessary laboratory and radiological examinations were demanded. Information was collected on disease duration, onset time, and patterns of neurological symptoms.
RESULTS
Forty-eight patients, including 42 females, aged 56.1±10.3 years were enroled.Central nervous system involvement was found in 34 patients. 85% of patients had generalized nerve manifestations, while local nerve manifestations were found in 77,5% of patients. The common neurological manifestation was headaches, then cognitive disorders, and the most common pattern of headache was migraine. Beck Depression Index showed a significant increase in the apathy evaluation scale.The study of cognitive changes showed a significant increase in the Mini-Mental State Examination (MMSE) index.Carotid Doppler showed the presence of injury in 42.4% of patients. The magnetic resonance imaging showed positive findings in 21 patients and positive evoked potentials in 52% of patients.
DISCUSSION
Studies showing the prevalence of Sjogren's neurological injury patterns are insufficient, but this was changed when the criteria for diagnosing Sjogren's syndrome was modified, and the definition of neurological traits in the context of the syndrome was expanded.The presence of a high rate of headaches, cognitive changes, and fatigue confirms that generalized nervous system injuries are more common than local injuries. Migraine was the most common pattern of headache found in patients with the syndrome compared with other patterns such as tension headaches and headaches due to medications, especially analgesics.This was associated with the presence of anti-SSA antibodies and Raynaud's phenomenon, which suggest that the headache mechanism may be due to vascular endothelial dysfunction or an immune-mediated inflammation injury of the neurovascular system.The changes that appeared on the MRI images suggested premotor cortex involvement rather than mesolimbic cortical impairment, and its presence was also associated with SSA antibody positivity, and it is caused by inflammation.
CONCLUSION
Primary Sjogren's syndrome should be considered as having any unspecified or specific neurological disorder.
PubMed: 37427219
DOI: 10.1097/MS9.0000000000000937 -
International Journal of Medical... 2023Acinar epithelial cell atrophy in secretory glands is a hallmark of primary Sjögren's syndrome (pSS), the cause of which is far from elucidated. We examined the role of...
Acinar epithelial cell atrophy in secretory glands is a hallmark of primary Sjögren's syndrome (pSS), the cause of which is far from elucidated. We examined the role of acinar atrophy by focusing on the metabolism of glandular epithelial cells and mitochondria in the pSS environment. After confirming the presence of a high-lactate environment in the labial glands of human pSS patients, we used the A253 cell line and NOD/Ltj mice as models to investigate the metabolic changes in salivary gland epithelial cells in a high-lactate environment and . We found that epithelial cells produced high levels of IL-6, IL-8, IFN-α, IFN-β and TNF-α and exhibited significant NF-κB and type I IFN-related pathway activation. The results confirmed that lactate damaged mitochondrial DNA (mtDNA) and led to its leakage, which subsequently activated the cGAS-STING pathway. Inflammatory cytokine production and pathway activation were inhibited and by the lactate scavenger sodium dichloroacetate (DCA). Our study provides new insights into the etiology and treatment of pSS from the perspective of cell metabolism.
Topics: Mice; Animals; Humans; Sjogren's Syndrome; Salivary Glands; DNA, Mitochondrial; Lactic Acid; Mice, Inbred NOD; Nucleotidyltransferases; Mitochondria
PubMed: 37786436
DOI: 10.7150/ijms.83801 -
Frontiers in Immunology 2024Macrophage activation syndrome (MAS) is a rare complication of autoimmune inflammatory rheumatic diseases (AIIRD) characterized by a progressive and life-threatening... (Review)
Review
Macrophage activation syndrome (MAS) is a rare complication of autoimmune inflammatory rheumatic diseases (AIIRD) characterized by a progressive and life-threatening condition with features including cytokine storm and hemophagocytosis. Predisposing factors are typically associated with microbial infections, genetic factors (distinct from typical genetically related hemophagocytic lymphohistiocytosis (HLH)), and inappropriate immune system overactivation. Clinical features include unremitting fever, generalized rash, hepatosplenomegaly, lymphadenopathy, anemia, worsening liver function, and neurological involvement. MAS can occur in various AIIRDs, including but not limited to systemic juvenile idiopathic arthritis (sJIA), adult-onset Still's disease (AOSD), systemic lupus erythematosus (SLE), Kawasaki disease (KD), juvenile dermatomyositis (JDM), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), etc. Although progress has been made in understanding the pathogenesis and treatment of MAS, it is important to recognize the differences between different diseases and the various treatment options available. This article summarizes the cell types and cytokines involved in MAS-related diseases, the heterogeneity, and treatment options, while also comparing it to genetically related HLH.
Topics: Humans; Macrophage Activation Syndrome; Disease Progression; Cytokines; Animals; Lymphohistiocytosis, Hemophagocytic
PubMed: 38736876
DOI: 10.3389/fimmu.2024.1389710 -
Pharmaceuticals (Basel, Switzerland) Aug 2023Xerostomia, commonly known as dry mouth, is a widespread oral health malfunction characterized by decreased salivary flow. This condition results in discomfort, impaired... (Review)
Review
Xerostomia, commonly known as dry mouth, is a widespread oral health malfunction characterized by decreased salivary flow. This condition results in discomfort, impaired speech and mastication, dysphagia, heightened susceptibility to oral infections, and ultimately, a diminished oral health-related quality of life. The etiology of xerostomia is multifaceted, with primary causes encompassing the use of xerostomic medications, radiation therapy to the head and neck, and systemic diseases such as Sjögren's syndrome. Consequently, there is a growing interest in devising management strategies to address this oral health issue, which presents significant challenges due to the intricate nature of saliva. Historically, natural products have served medicinal purposes, and in contemporary pharmaceutical research and development, they continue to play a crucial role, including the treatment of xerostomia. In this context, the present review aims to provide an overview of the current state of knowledge regarding natural compounds and extracts for xerostomia treatment, paving the way for developing novel therapeutic strategies for this common oral health issue.
PubMed: 37631049
DOI: 10.3390/ph16081136 -
Normal and Sjogren's syndrome models of the murine lacrimal gland studied at single-cell resolution.Proceedings of the National Academy of... Oct 2023The lacrimal gland is of central interest in ophthalmology both as the source of the aqueous component of tear fluid and as the site of autoimmune pathology in the...
The lacrimal gland is of central interest in ophthalmology both as the source of the aqueous component of tear fluid and as the site of autoimmune pathology in the context of Sjogren's syndrome (SjS). To provide a foundational description of mouse lacrimal gland cell types and their patterns of gene expression, we have analyzed single-cell transcriptomes from wild-type (Balb/c) mice and from two genetically based SjS models, and (nonobese diabetic), and defined the localization of multiple cell-type-specific protein and mRNA markers. This analysis has uncovered a previously undescribed cell type, Car6+ cells, which are located at the junction of the acini and the connecting ducts. More than a dozen secreted polypeptides that are likely to be components of tear fluid are expressed by acinar cells and show pronounced sex differences in expression. Additional examples of gene expression heterogeneity within a single cell type were identified, including a gradient of Claudin4 along the length of the ductal system and cell-to-cell heterogeneity in transcription factor expression within acinar and myoepithelial cells. The patterns of expression of channels, transporters, and pumps in acinar, Car6+, and ductal cells make strong predictions regarding the mechanisms of water and electrolyte secretion. In and lacrimal glands, distinctive changes in parenchymal gene expression and in immune cell subsets reveal widespread interferon responses, a T cell-dominated infiltrate in the model, and a mixed B cell and T cell infiltrate in the model.
Topics: Female; Mice; Male; Animals; Sjogren's Syndrome; Lacrimal Apparatus; Mice, Inbred MRL lpr; Mice, Inbred NOD; Mice, Inbred BALB C; Disease Models, Animal
PubMed: 37812717
DOI: 10.1073/pnas.2311983120 -
Frontiers in Immunology 2023Primary Sjogren's syndrome (pSS) is a prototypical systemic autoimmune disease characterised by lymphocyte infiltration and immune-complex deposition in multiple organs....
BACKGROUND
Primary Sjogren's syndrome (pSS) is a prototypical systemic autoimmune disease characterised by lymphocyte infiltration and immune-complex deposition in multiple organs. The specific distribution of immune cell populations and their relationship with mitochondria remain unknown.
METHODS
Histological analysis was performed to assess the specific distribution of innate and adaptive immune cell populations in labial salivary gland (LSG) samples from 30 patients with pSS and 13 patients with non-pSS. The ultrastructural morphometric features of mitochondria within immune cells were observed under the transmission electron microscope (TEM). RNA sequencing was performed on LSG samples from 40 patients with pSS and 7 non-pSS patients. The Single-sample Gene Set Enrichment Analysis (ssGSEA), ESTIMATE, and CIBERSORT algorithms and Pearson correlation coefficients were used to examine the relationship between mitochondria-related genes and immune infiltration. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify the mitochondria-specific genes and the related pathways based on the immune cell types.
RESULTS
HE staining revealed a massive infiltration of plasma cells with abundant immunoglobulin protein distributed around phenotypically normal-appearing acinar and ductal tissues of patients with pSS. Immunohistochemical analyses revealed that innate immune cells (macrophages, eosinophils and NK cells) were distributed throughout the glandular tissue. Dominant adaptive immune cell infiltration composed of B cells, CD4T cells and CD8 T cells or ectopic lymphoid follicle-like structures were observed in the LSGs of patients with pSS. TEM validated the swelling of mitochondria with disorganised cristae in some lymphocytes that had invaded the glandular tissue. Subsequently, bioinformatic analysis revealed that innate and adaptive immune cells were associated with different mitochondrial metabolism pathways. Mitochondrial electron transport and respiratory chain complexes in the glandular microenvironment were positively correlated with innate immune cells, whereas amino acid and nucleic acid metabolism were negatively correlated with adaptive immune cells. In addition, mitochondrial biogenesis and mitochondrial apoptosis in the glandular microenvironment were closely associated with adaptive immune cells.
CONCLUSION
Innate and adaptive immune cells have distinct distribution profiles in the salivary gland tissues of patients with pSS and are associated with different mitochondrial metabolic pathways, which may contribute to disease progression.
Topics: Humans; Salivary Glands; Sjogren's Syndrome; CD8-Positive T-Lymphocytes; Mitochondria; Metabolome
PubMed: 37497211
DOI: 10.3389/fimmu.2023.1156774 -
Journal of Clinical Medicine Jul 2023Fatigue is the most commonly reported and debilitating extraglandular symptom of primary Sjögren's syndrome (pSS). Fatigue and exertional intolerance are hallmark...
Fatigue is the most commonly reported and debilitating extraglandular symptom of primary Sjögren's syndrome (pSS). Fatigue and exertional intolerance are hallmark symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We aimed to characterize fatigue and further symptoms among pSS patients and to determine whether there is a symptom overlap in pSS and ME/CFS. In 19 patients with pSS, we assessed pSS symptom severity and disease activity via questionnaires as well as the Canadian Consensus Criteria (CCC) for ME/CFS. Hand grip strength (HGS) and levels of α1-, α2-, β1-, β2-, M3- and M4-receptor-autoantibodies were measured. A subgroup of pSS patients exhibited severe fatigue and had higher severity of pain ( = 0.045), depression ( = 0.021) and sleep disturbances ( = 0.020) compared to those with less fatigue. Four of eighteen pSS patients fulfilled the CCC. HGS parameters strongly correlated with fatigue severity ( < 0.05), but strength fully recovered one hour after exertion in contrast to ME/CFS. Levels of β1-, β2- and M4-receptor-autoantibodies were elevated and correlated significantly with disease activity assessed by the ESSDAI ( < 0.05), but not fatigue severity. Only a minor subgroup of pSS patients fulfills the CCC, and post exertional malaise (PEM) is atypical, as it is primarily triggered by mental/emotional but not physical exertion. HGS assessment is an objective measure to assess overall fatigue severity.
PubMed: 37568396
DOI: 10.3390/jcm12154994 -
Global Cardiology Science & Practice Mar 2024Hydroxychloroquine (HCQ), which was initially used as an antimalarial drug, is now being used to treat other illnesses, especially rheumatic autoimmune disorders such... (Review)
Review
Hydroxychloroquine (HCQ), which was initially used as an antimalarial drug, is now being used to treat other illnesses, especially rheumatic autoimmune disorders such as systemic lupus erythematosus, primary Sjögren's syndrome, and rheumatoid arthritis, because it is safe, effective, and cost efficient. This drug has shown high efficacy and has become the first-line treatment for many of these diseases. Although HCQ has many therapeutic effects, it has unfortunately shown some complications, especially with its long-term use. One of these side effects is arrhythmia through prolongation of the QT interval. This narrative literature review focuses on the effects of HCQ on the QT interval in patients with rheumatologic diseases who have been prescribed this drug. In particular, we will focus on the increased risk of arrhythmia when HCQ is administered with other drugs, such as azithromycin and many others, along with drug-drug interactions. In addition, we investigated the safety of this drug in pregnant women.
PubMed: 38746066
DOI: 10.21542/gcsp.2024.17 -
Annals of the Rheumatic Diseases Feb 2024To evaluate the safety and efficacy of remibrutinib in patients with moderate-to-severe Sjögren's syndrome (SjS) in a phase 2 randomised, double-blind trial... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of remibrutinib, a selective potent oral BTK inhibitor, in Sjögren's syndrome: results from a randomised, double-blind, placebo-controlled phase 2 trial.
OBJECTIVES
To evaluate the safety and efficacy of remibrutinib in patients with moderate-to-severe Sjögren's syndrome (SjS) in a phase 2 randomised, double-blind trial (NCT04035668; LOUiSSE (LOU064 in Sjögren's Syndrome) study).
METHODS
Eligible patients fulfilling 2016 American College of Rheumatology/European League Against Rheumatism (EULAR) criteria for SjS, positive for anti-Ro/Sjögren's syndrome-related antigen A antibodies, with moderate-to-severe disease activity (EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) (based on weighted score) ≥ 5, EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) ≥ 5) received remibrutinib (100 mg) either one or two times a day, or placebo for the 24-week study treatment period. The primary endpoint was change from baseline in ESSDAI at week 24. Key secondary endpoints included change from baseline in ESSDAI over time, change from baseline in ESSPRI over time and safety of remibrutinib in SjS. Key exploratory endpoints included changes to the salivary flow rate, soluble biomarkers, blood transcriptomic and serum proteomic profiles.
RESULTS
Remibrutinib significantly improved ESSDAI score in patients with SjS over 24 weeks compared with placebo (ΔESSDAI -2.86, p=0.003). No treatment effect was observed in ESSPRI score (ΔESSPRI 0.17, p=0.663). There was a trend towards improvement of unstimulated salivary flow with remibrutinib compared with placebo over 24 weeks. Remibrutinib had a favourable safety profile in patients with SjS over 24 weeks. Remibrutinib induced significant changes in gene expression in blood, and serum protein abundance compared with placebo.
CONCLUSIONS
These data show preliminary efficacy and favourable safety of remibrutinib in a phase 2 trial for SjS.
Topics: Humans; Sjogren's Syndrome; Proteomics; Antibodies; Severity of Illness Index; Pyrimidines
PubMed: 37932009
DOI: 10.1136/ard-2023-224691