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European Journal of Ophthalmology Nov 2022Sjögren's syndrome is an autoimmune disease, and its important feature is the lymphocyte infiltration of exocrine glands, including lacrimal glands. It contributes to... (Review)
Review
BACKGROUND
Sjögren's syndrome is an autoimmune disease, and its important feature is the lymphocyte infiltration of exocrine glands, including lacrimal glands. It contributes to defects of their activity and causes that one of the main manifestation of Sjögren's syndrome is dry eye. Unfortunately, the discrimination between dry eye related and non-related to Sjögren's syndrome is difficult at the initial stages of diseases. In addition, the available agents for the treatment of Sjögren's syndrome-related dry eye have limited efficacy.
AIM
The purpose of this study was to describe and emphasize differences between Sjögren's Syndrome-related dry eye and non-Sjögren's Syndrome-related dry eye together with the determination of novel therapeutic options for Sjögren's Syndrome-related dry eye.
METHOD
A review of the relevant papers describing characteristics of Sjögren's Syndrome-related dry eye and its therapy was conducted. This article is based on both pre-clinical and clinical evidences.
RESULTS
On the basis of our analysis, we indicated differences between Sjögren's Syndrome-related dry eye and non-Sjögren's Syndrome-related dry eye. Moreover, there are some novel markers that could be used in the diagnosis of Sjögren's Syndrome-related dry eye. In addition, expect artificial tear, other agents e.g. hydroxychloroquine can be effective in therapy of disease.
CONCLUSIONS
Sjögren's Syndrome-related dry eye is a disorder, whose diagnosis may be difficult and mistaken for non-Sjögren's Syndrome-related dry eye. However, Sjögren's Syndrome-related dry eye has some specific features. In addition, the development of newer and safer therapeutic agents for Sjögren's syndrome-related dry eye is needed, and therefore further clinical, randomized studies are necessary.
Topics: Dry Eye Syndromes; Humans; Hydroxychloroquine; Lubricant Eye Drops; Sjogren's Syndrome; Tears
PubMed: 35354331
DOI: 10.1177/11206721221091375 -
Genes Mar 2021Sjögren's syndrome (SS) is a chronic, progressive, inflammatory, autoimmune disease, characterized by the lymphocyte infiltration of exocrine glands, especially the... (Review)
Review
Sjögren's syndrome (SS) is a chronic, progressive, inflammatory, autoimmune disease, characterized by the lymphocyte infiltration of exocrine glands, especially the lacrimal and salivary, with their consequent destruction. The onset of primary SS (pSS) may remain misunderstood for several years. It usually presents with different types of severity, e.g., dry eye and dry mouth symptoms, due to early involvement of the lacrimal and salivary glands, which may be associated with parotid enlargement and dry eye; keratoconjunctivitis sicca (KCS) is its most common ocular manifestation. It is still doubtful if the extent ocular surface manifestations are secondary to lacrimal or meibomian gland involvement or to the targeting of corneal and conjunctival autoantigens. SS is the most representative cause of aqueous deficient dry eye, and the primary role of the inflammatory process was evidenced. Recent scientific progress in understanding the numerous factors involved in the pathogenesis of pSS was registered, but the exact mechanisms involved still need to be clarified. The unquestionable role of both the innate and adaptive immune system, participating actively in the induction and evolution of the disease, was recognized. The ocular surface inflammation is a central mechanism in pSS leading to the decrease of lacrimal secretion and keratoconjunctival alterations. However, there are controversies about whether the ocular surface involvement is a direct autoimmune target or secondary to the inflammatory process in the lacrimal gland. In this review, we aimed to present actual knowledge relative to the pathogenesis of the pSS, considering the role of innate immunity, adaptive immunity, and genetics.
Topics: Adaptive Immunity; Humans; Immunity, Innate; Severity of Illness Index; Sjogren's Syndrome
PubMed: 33806489
DOI: 10.3390/genes12030365 -
The Lancet. Rheumatology Apr 2024
Topics: Humans; Sjogren's Syndrome
PubMed: 38508816
DOI: 10.1016/S2665-9913(24)00061-4 -
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 -
Revue Medicale Suisse Apr 2022Sjögren's syndrome (SS) is a systemic autoimmune disease affecting the lacrimal and salivary glands. In up to one third of patients, SS may be complicated by... (Review)
Review
Sjögren's syndrome (SS) is a systemic autoimmune disease affecting the lacrimal and salivary glands. In up to one third of patients, SS may be complicated by potentially severe extra-glandular visceral involvement, which can be life-threatening. Diagnosis is often difficult based on a combination of clinical and biological evidence. The development of new imaging techniques can now help the clinician in his diagnostic approach. Long considered incurable, new medical and surgical treatments are being studied and are potentially promising. Paramedical management and regular physical activity are also essential and contribute to the improvement of patients' fatigue. The objective of this article is to review the main clinical manifestations as well as the diagnostic and therapeutic novelties developed in recent years.
Topics: Fatigue; Humans; Lacrimal Apparatus; Salivary Glands; Sjogren's Syndrome
PubMed: 35385615
DOI: 10.53738/REVMED.2022.18.776.646 -
Clinical and Experimental Rheumatology 2020Glucocorticoids (GCs) are involved in several physiological processes such as metabolism, water and electrolyte balance, growth, cardiovascular and cognitive functions,... (Review)
Review
Glucocorticoids (GCs) are involved in several physiological processes such as metabolism, water and electrolyte balance, growth, cardiovascular and cognitive functions, reproduction. Furthermore, they exert different effects on innate and adaptive immune cells. Due to their anti-inflammatory and immunosuppressive functions, these drugs are largely used for the treatment of inflammatory and autoimmune diseases. In comparison to other autoimmune rheumatic diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), to date no reliable evidence is available for the use of systemic GCs in Sjögren's syndrome (SS), which is still based on case reports, case studies, retrospective or prospective studies and a small number of randomised controlled trials (RCTs). Despite this gap in our knowledge, GCs are commonly used in SS for glandular, joint, cutaneous, lung, haematological, renal, neurological involvement. More recently, some sets of recommendations for the management of SS have provided a few pieces of advice regarding the use of GCs in this condition. Future studies should not neglect the role of GCs, as this traditional therapeutic weapon can still have a role in the management of SS. Accordingly, this review will address and discuss the use of systemic GCs in isolated or primary SS.
Topics: Arthritis, Rheumatoid; Autoimmune Diseases; Glucocorticoids; Humans; Lupus Erythematosus, Systemic; Sjogren's Syndrome
PubMed: 33095141
DOI: No ID Found -
Clinical and Experimental Rheumatology Dec 2023The link between immune cell function and cell metabolic reprogramming is currently known under the term "immunometabolism". Similarly to the Warburg's effect described... (Review)
Review
The link between immune cell function and cell metabolic reprogramming is currently known under the term "immunometabolism". Similarly to the Warburg's effect described in cancer cells, in activated immune cells an up-regulation of specific metabolic pathways has been described and seems to be pathogenic in different inflammatory conditions.Sjӧgren's syndrome (SS) is a systemic autoimmune disease that affects the exocrine glands and is characterised by a progressive loss of secretory function. Despite the increasing amount of evidence on the ability of metabolism in regulating cell behaviour in inflammatory or tumoral conditions, the field of metabolism in SS is still for the most part unexplored.The aim of this review is to summarise currently available studies evaluating cell metabolism in SS with a particular focus on the possible pathogenic role of metabolic changes in immune and non-immune cells in this condition.
Topics: Humans; Sjogren's Syndrome
PubMed: 38149514
DOI: 10.55563/clinexprheumatol/hhbqej -
La Revue de Medecine Interne Aug 2023Sjögren's disease (SD), also known as Sjögren's syndrome (SS) or Gougerot-Sjögren's syndrome in France, is a rare systemic autoimmune disease in its primary form and... (Review)
Review
Sjögren's disease (SD), also known as Sjögren's syndrome (SS) or Gougerot-Sjögren's syndrome in France, is a rare systemic autoimmune disease in its primary form and is characterised by tropism for the exocrine glandular epithelia, particularly the salivary and lacrimal glands. The lymphocytic infiltration of these epithelia will clinically translate into a dry syndrome which, associated with fatigue and pain, constitutes the symptom triad of the disease. In about one third of patients, SD is associated with systemic complications that can affect the joints, skin, lungs, kidneys, central or peripheral nervous system, and lymphoid organs with an increased risk of B-cell lymphoma. SD affects women more frequently than men (9/1). The peak frequency is around the age of 50. However, the disease can occur at any age, with paediatric forms occurring even though they remain rare. SD can occur alone or in association with other systemic autoimmune diseases. In its isolated or primary form, the prevalence of SD is estimated to be between 1 per 1000 and 1 per 10,000 inhabitants. The most recent classification criteria were developed in 2016 by EULAR and ACR. The course and prognosis of the disease are highly variable and depend on the presence of systemic involvement and the severity of the dryness of the eyes and mouth. The current approach is therefore to identify at an early stage those patients most at risk of systemic complications or lymphoma, who require close follow-up. On the other hand, regular monitoring of the ophthalmological damage and of the dental status should be ensured to reduce the consequences.
Topics: Humans; Female; Child; Sjogren's Syndrome; Eye; Skin; France
PubMed: 37453854
DOI: 10.1016/j.revmed.2023.07.001 -
Scientific Reports Dec 2021Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The...
Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population.
Topics: Autoantibodies; DNA Methylation; Epigenomics; Female; Gene Expression; Gene Expression Regulation; Genetic Variation; HLA Antigens; Humans; Interferons; Male; Sjogren's Syndrome
PubMed: 34857786
DOI: 10.1038/s41598-021-01324-0 -
Scientific Reports Nov 2023We compared the efficacy and safety of autologous-serum (AS) and platelet-rich plasma (PRP) eye drops for dry eye (DE) treatment in primary Sjögren's syndrome (SS).... (Randomized Controlled Trial)
Randomized Controlled Trial
We compared the efficacy and safety of autologous-serum (AS) and platelet-rich plasma (PRP) eye drops for dry eye (DE) treatment in primary Sjögren's syndrome (SS). This prospective, randomized, double-blinded clinical study included patients diagnosed with primary SS DE. Thirty-eight participants were randomly assigned to the AS or PRP groups. Corneal and conjunctival staining scores, Schirmer I test, tear film break-up time (TBUT), and ocular surface disease index (OSDI) scores were evaluated at 4 and 12 weeks. Conjunctival impression cytology (CIC) metaplasia grade and goblet cell density grade at 12 weeks were compared with those at baseline. Corneal and conjunctival staining scores and TBUT significantly improved at 4 and 12 weeks in both groups (all p < 0.005). No significant difference between the AS and PRP groups was observed at 4 and 12 weeks. The Schirmer I values, OSDI scores, CIC metaplasia grade, and goblet cell density grade did not significantly change at 4 and 12 weeks in either group. Both AS and PRP eye drops are effective for primary SS DE without a significant difference. Considering that the preparation time of PRP is shorter than that of AS, PRP can be a good alternative treatment for primary SS DE.
Topics: Humans; Dry Eye Syndromes; Metaplasia; Ophthalmic Solutions; Platelet-Rich Plasma; Prospective Studies; Sjogren's Syndrome; Tears
PubMed: 37935760
DOI: 10.1038/s41598-023-46671-2