Sjögren Syndrome: New Insights in the Pathogenesis and Role of Nuclear Medicine

Kelly, Anzola Luz; Nelson, Rivera Jose; Sara, Ramírez

doi:10.3390/jcm11175227

Cited by 11 publications

(5 citation statements)

References 82 publications

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“…While attempting to regulate the autoimmune response, immune cells can inadvertently contribute to the damage to glandular tissues. Additionally, the chronic inflammation associated with SjS can have systemic effects beyond the glands, impacting various organs and tissues throughout the body ( 7 , 118 ). Recent studies show that DNA methylation is applied to many cell types implicated in the pathophysiology of SjS.…”

Section: Role Of Dna Methylation In Sjsmentioning

confidence: 99%

Functional significance of DNA methylation: epigenetic insights into Sjögren’s syndrome

Wang,

Riaz,

Wang

et al. 2024

Front. Immunol.

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Sjögren’s syndrome (SjS) is a systemic, highly diverse, and chronic autoimmune disease with a significant global prevalence. It is a complex condition that requires careful management and monitoring. Recent research indicates that epigenetic mechanisms contribute to the pathophysiology of SjS by modulating gene expression and genome stability. DNA methylation, a form of epigenetic modification, is the fundamental mechanism that modifies the expression of various genes by modifying the transcriptional availability of regulatory regions within the genome. In general, adding a methyl group to DNA is linked with the inhibition of genes because it changes the chromatin structure. DNA methylation changes the fate of multiple immune cells, such as it leads to the transition of naïve lymphocytes to effector lymphocytes. A lack of central epigenetic enzymes frequently results in abnormal immune activation. Alterations in epigenetic modifications within immune cells or salivary gland epithelial cells are frequently detected during the pathogenesis of SjS, representing a robust association with autoimmune responses. The analysis of genome methylation is a beneficial tool for establishing connections between epigenetic changes within different cell types and their association with SjS. In various studies related to SjS, most differentially methylated regions are in the human leukocyte antigen (HLA) locus. Notably, the demethylation of various sites in the genome is often observed in SjS patients. The most strongly linked differentially methylated regions in SjS patients are found within genes regulated by type I interferon. This demethylation process is partly related to B-cell infiltration and disease progression. In addition, DNA demethylation of the runt-related transcription factor (RUNX1) gene, lymphotoxin-α (LTA), and myxovirus resistance protein A (MxA) is associated with SjS. It may assist the early diagnosis of SjS by serving as a potential biomarker. Therefore, this review offers a detailed insight into the function of DNA methylation in SjS and helps researchers to identify potential biomarkers in diagnosis, prognosis, and therapeutic targets.

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Section: Role Of Dna Methylation In Sjsmentioning

confidence: 99%

Functional significance of DNA methylation: epigenetic insights into Sjögren’s syndrome

Wang,

Riaz,

Wang

et al. 2024

Front. Immunol.

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“…SS is also associated with human immunodeficiency syndrome, hepatitis C and COVID-19 infection, chronic graft-versus-host disease after allogeneic bone marrow transplantation, neoplastic and myeloblastic syndromes, chronic biliary cirrhosis, fibromyalgia, and chronic fatigue syndrome. Predictive models significantly associate SS with preceding female hormone replacement therapy, fibromyalgia, lymphoma, body mass index, osteoporosis, and diabetes [ 3 , 4 , 5 , 6 ]. The precise pathogenic mechanisms of SS remain incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

“…This hinders the proper management of the syndrome, which is mainly symptomatic. Inflammation induced by lymphocytic infiltration (specifically CD4+ T and B cells, and plasma cells) of the salivary, lacrimal, nasal, and sebaceous glands or vaginal mucosa (acinar and ductal cells) and other tissues is a pathognomonic hallmark, with progressive damage to these tissues and reduced secretions, culminating in severe dryness (Sicca syndrome; xerophthalmia, xerostomia, and xeroderma) and systemic symptoms [ 2 , 4 ]. Xerophthalmia is unrelated to Sjögren’s syndrome and is induced by vitamin A deficiency, although vitamin A and vitamin D deficiencies have been linked with the syndrome.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Targets in the Management of Dry Eye Disease Associated with Sjögren’s Syndrome: An Updated Review of Current Insights and Future Perspectives

Almulhim

2024

JCM

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Dry eye disease (DED) is a continuing medical challenge, further worsened in the autoimmune inflammatory hyperactivation milieu of Sjögren’s syndrome (SS) due to disturbances to innate and adaptive immunity with malfunctioning neuro-endocrine control. However, the pathogenetic mechanisms of SS DED are not fully established. This review summarized the available evidence, from systematic reviews, meta-analyses, and randomized clinical trials, for the efficacy and safety of the available ocular therapeutics for the management of SS DED. Relevant studies were obtained from major databases using appropriate keywords. The available largely empirical symptomatic, supportive, and restorative treatments have significant limitations as they do not alter local and systemic disease progression. Topical therapies have expanded to include biologics, surgical approaches, scleral lens fitting, the management of lid margin disease, systemic treatments, nutritional support, and the transplantation of stem cells. They are not curative, as they cannot permanently restore the ocular surface’s homeostasis. These approaches are efficacious in the short term in most studies, with more significant variability in outcome measures among studies in the long term. This review offers an interdisciplinary perspective that enriches our understanding of SS DED. This updated review addresses current knowledge gaps and identifies promising areas for future research to overcome this medical challenge.

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“…This chronic, systemic autoimmune disease is characterised by reduced saliva and lacrimal fluid production, causing sicca symptoms of the mouth and eyes. Characteristic is the infiltrate of immune cells in the salivary glands, mostly located around the ducts that transport saliva (15,16). Several studies have been conducted to determine the value of 18 F-FDG-PET/CT in discriminating between pSS and individuals without pSS (17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Salivary gland 18F-FDG-PET/CT uptake patterns in Sjögren's syndrome and giant cell arteritis patients

Grootelaar,

van Ginkel,

Nienhuis

et al. 2023

Clinical and Experimental Rheumatology

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ObjectiveWide variety in salivary gland 18 F-FDG-uptake is observed in the general population. A general consensus about the usefulness of 18 F-FDG-PET/CT to detect salivary gland inflammatory conditions, such as in primary Sjögren's syndrome (pSS), is not yet clear. This study aimed to investigate whether there are differences in uptake of 18 F-FDG in salivary glands among two autoimmune groups [pSS, giant cell arteritis (GCA)] and a non-autoimmune group (lung cancer). Methods PSS patients aged ≥50 years who underwent 18 F-FDG-PET/CT were included and age-matched with GCA patients and a non-autoimmune control group (lung cancer patients). Scans were visually evaluated and quantitative analysiswas performed by measuring standardised uptake values (SUV) within salivary glands and lacrimal glands.For GCA patients, arteries in the vicinity of the parotid and submandibular gland were assessed for positivity. 18 F-FDG-uptake in the parotid or submandibular gland, compared to the other two groups. For the tubarial gland, significantly higher SUV max was found in the pSS patient group. Interestingly, GCA patients had significantly higher SUV max in the submandibular gland than the other two groups. Results PSS patients did not show increasedVisual 18 F-FDG-positivity of cranial arteries related to the parotid and submandibular glands was associated with significantly higher SUV max in salivary glands of GCA patients. ConclusionAlthough 18 F-FDG-uptake was not increased in parotid and submandibular glands of pSS patients, increased 18 F-FDG-uptake in tubarial glands of pSS patients might indicate a role for these glands in pSS.Furthermore, parotid and submandibular glands may be affected by local vasculitis in GCA.

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Sjögren Syndrome: New Insights in the Pathogenesis and Role of Nuclear Medicine

Cited by 11 publications

References 82 publications

Functional significance of DNA methylation: epigenetic insights into Sjögren’s syndrome

Functional significance of DNA methylation: epigenetic insights into Sjögren’s syndrome

Therapeutic Targets in the Management of Dry Eye Disease Associated with Sjögren’s Syndrome: An Updated Review of Current Insights and Future Perspectives

Salivary gland 18F-FDG-PET/CT uptake patterns in Sjögren's syndrome and giant cell arteritis patients

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