Current State of Knowledge on Primary Sjögren’s Syndrome, an Autoimmune Exocrinopathy

Journal of Clinical Medicine, Год журнала: 2020, Номер 9(7), С. 2299 - 2299

Опубликована: Июль 20, 2020

Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune rheumatic disease characterized by lymphoplasmacytic infiltration of the salivary and lacrimal glands, whereby sicca and/or manifestations are clinical hallmarks, associated with particular autoantibody profile. pSS most frequent connective tissue after rheumatoid arthritis, affecting 0.3-3% population. Women more prone to develop than men, sex ratio 9:1. Considered in past as innocent collateral passive victims autoimmunity, epithelial cells glands now known play an active role pathogenesis disease. The aetiology "autoimmune epithelitis" still remains unknown, but certainly involves genetic, environmental hormonal factors. Later during evolution, subsequent activation B can lead development or non-Hodgkin's lymphoma. aim present comprehensive review provide current state knowledge on pSS. addresses complications disease, diagnostic workup, pathogenic mechanisms therapeutic approaches.

Язык: Английский

---

Involvement of long noncoding RNAs in the pathogenesis of autoimmune diseases

Journal of Translational Autoimmunity, Год журнала: 2020, Номер 3, С. 100044 - 100044

Опубликована: Янв. 1, 2020

Autoimmune diseases are a group of heterogeneous disorders characterized by damage to various organs caused abnormal innate and adaptive immune responses. The pathogenesis autoimmune is extremely complicated has not yet been fully elucidated. Long noncoding RNAs (lncRNAs), which defined as transcripts containing more than 200 nucleotides with no protein-coding capacity, emerging important regulators gene expression via epigenetic modification, transcriptional regulation posttranscriptional regulation. Accumulating evidence demonstrated that lncRNAs play key role in the immunological functions autoimmunity. In this review, we discuss molecular mechanisms regulate recent findings regarding involvement many human diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), idiopathic inflammatory myopathy (IIM), sclerosis (SSc) Sjögren's syndrome (pSS).

Язык: Английский

---

Molecular mechanism of lncRNAs in pathogenesis and diagnosis of auto-immune diseases, with a special focus on lncRNA-based therapeutic approaches

Life Sciences, Год журнала: 2023, Номер 336, С. 122322 - 122322

Опубликована: Дек. 1, 2023

Язык: Английский

---

Functional Genomics Using High‐Throughput Methods for Salivary Analysis in Sjögren's Disease

Oral Diseases, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

ABSTRACT Objectives Primary Sjögren's disease (SjD) is a slow‐progressing autoimmune that affects salivary and lacrimal glands, causing dry eyes (xerophthalmia) mouth (xerostomia). Diagnosing SjD involves clinical, serological, histological assessments, but reliable biomarkers are lacking. Methods This study analyzed the metabolic proteomic profiles of 19 female patients (based on ACR‐EULAR criteria) compared to 20 healthy individuals. Saliva blood samples were using mass spectrometry chromatography. Proteomic analysis was performed with nanoElute nanoflow system coupled timsTof‐Pro spectrometer, profiling GC‐TOF/MS Pegasus HT. Results Statistical tests identified significant differences in metabolites proteins between controls. Metabolome revealed changes amino acid synthesis, purine lipid metabolism, exposure external compounds. indicated immune‐related inflammatory metabolism. GNAI2, B2MG, NGAL, SLUR2, HS90, SODC, A2GL emerged as potential for SjD. Conclusion demonstrates high‐performance techniques identifying diagnosis prognosis. Data available via ProteomeXchange (PXD055629).

Язык: Английский

---

Non-coding RNAs in immunoregulation and autoimmunity: Technological advances and critical limitations

Journal of Autoimmunity, Год журнала: 2022, Номер 134, С. 102982 - 102982

Опубликована: Дек. 31, 2022

Immune cell function is critically dependent on precise control over transcriptional output from the genome. In this respect, integration of environmental signals that regulate gene expression, specifically by transcription factors, enhancer DNA elements, genome topography and non-coding RNAs (ncRNAs), are key components. The first three have been extensively investigated. Even though represent vast majority cellular RNA species, class remains historically understudied. This partly because a lag in technological bioinformatic innovations capable identifying accurately measuring their expression. Nevertheless, recent progress domain has enabled profusion publications novel sub-types ncRNAs studies directly addressing human health disease. Many ncRNAs, including circular RNAs, now demonstrated to play functions regulation immune cells show associations with immune-mediated diseases. Some may as biomarkers disease, aiding diagnostics estimating response treatment, while others direct role pathogenesis Importantly, some relatively stable amenable therapeutic targeting, for example through therapy. Here, we provide an overview review advances enable study hold substantial promise future. We context-specific examples examining four prototypical autoimmune diseases, rheumatoid arthritis, psoriasis, inflammatory bowel disease multiple sclerosis. anticipate utility mechanistic roles these autoimmunity will be further elucidated near

Язык: Английский

---

Dysregulated long non-coding RNA in Sjögren’s disease impacts both interferon and adaptive immune responses

RMD Open, Год журнала: 2022, Номер 8(2), С. e002672 - e002672

Опубликована: Ноя. 1, 2022

Objective Sjögren’s disease (SjD) is an autoimmune characterised by inflammatory destruction of exocrine glands. Patients with autoantibodies to Ro/SSA (SjD Ro+ ) exhibit more severe disease. Long non-coding RNAs (lncRNAs) are a functionally diverse class non-protein-coding whose role in pathology has not been well characterised. Methods Whole blood RNA-sequencing (RNA-seq) was performed on SjD cases (n=23 negative Ro− ); n=27 positive and healthy controls (HCs; n=27). Bioinformatics pathway analyses differentially expressed (DE) transcripts (log 2 fold change ≥2 or ≤0.5; p adj <0.05) were used predict lncRNA function. LINC01871 RNA-seq HSB-2 cells CRISPR-targeted deletion ( −/ − vitro stimulation assays. Results revealed autoantibody-specific transcription profiles disproportionate downregulation DE relative HCs. Sixteen lncRNAs exhibited correlated expression the interferon (IFN)-regulated gene, RSAD2 , (r≥0.65 ≤−0.6); four antisense IFN-regulated immune cell lines. upregulated all cases. implicated roles cytotoxic function, differentiation IFNγ induction. induced myeloid line regulated calcineurin/NFAT T receptor (TCR) signalling primary human cells. Conclusion influences many genes growth factors, inducible, calcineurin TCR ligand engagement. Altered may influence dysregulated pathways SjD.

Язык: Английский

---

Long Non-Coding RNAs in Sjögren’s Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(10), С. 5162 - 5162

Опубликована: Май 9, 2024

Sjögren's disease (SjD) is a heterogeneous autoimmune characterized by severe dryness of mucosal surfaces, particularly the mouth and eyes; fatigue; chronic pain. Chronic inflammation salivary lacrimal glands, auto-antibody formation, extra-glandular manifestations occur in subsets patients with SjD. An aberrant expression long, non-coding RNAs (lncRNAs) has been described many diseases, including Here, we review current literature on lncRNAs SjD their role regulating X chromosome inactivation, immune modulatory functions, potential as biomarkers.

Язык: Английский

---

lncRNA expression profiles related to apoptosis and autophagy in peripheral blood mononuclear cells of patients with rheumatoid arthritis

FEBS Open Bio, Год журнала: 2020, Номер 10(8), С. 1642 - 1654

Опубликована: Июнь 22, 2020

Long noncoding RNAs (lncRNAs) are >200‐bp molecules that do not generally code for proteins. Human lncRNAs have well‐characterized roles in gene expression regulation, particularly with regard to protein‐coding genes, and their dysregulation has been linked disease. Here, we set out investigate changes the of related apoptosis autophagy peripheral blood mononuclear cells (PBMCs) rheumatoid arthritis (RA). In addition, aimed correlate lncRNA profiles clinical indexes self‐perception patients (SPP). To this end, employed RNA sequencing PBMCs from three RA healthy controls. We used bioinformatics screen several dysregulated autophagy. validate key candidates, performed quantitative reverse transcriptase–PCR on 20 found seven (MAPKAPK5‐AS1, ENST00000619282, C5orf17, LINC01189, LINC01006, DSCR9 MIR22HG) was significantly altered RA. Receiver operating characteristic curve analysis suggested MIR22HG [area under (AUC) = 0.846, P 0.000], (AUC 0.783, 0.005), LINC01189 0.677, 0.034), MAPKAPK5‐AS1 0.644, 0.025) ENST00000619282 0.636, 0.043) potential biomarkers Spearman's correlation revealed selected correlated SPP. Therefore, highlight some may serve as diagnosis monitoring progression, which also

Язык: Английский

---

Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Primary Sjögren’s Syndrome Salivary Glands

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Ноя. 29, 2021

Sjögren’s Syndrome (SS) is a chronic autoimmune disease of unknown etiology which primarily affects the salivary and lacrimal glands resulting in loss secretory function. Treatment options for SS have been hampered due to lack better understanding underlying gene regulatory circuitry interplay between myriad pathological cellular states that contribute gland dysfunction. To elucidate molecular nature SS, we performed RNA-sequencing analysis submandibular (SMG) well-established primary (pSS) mouse model. Our comprehensive examination global expression comparative analyses with additional models human datasets, identified number important pathways networks are relevant pathobiology. complement these studies, single-cell RNA sequencing examine identify heterogeneity diseased cell populations SMG. Interrogation transcriptomes has shed light on diversity immune cells dysregulated importantly, revealed an activated state epithelial mediated responses. Overall, our broad studies not only key pathways, mediators new biomarkers, but also uncovered complex SMG likely drive progression SS. These newly discovered insights into mechanisms will inform targeted therapeutic discoveries.

Язык: Английский

---

Management of Sjögren's Syndrome: Present Issues and Future Perspectives

Frontiers in Medicine, Год журнала: 2021, Номер 8

Опубликована: Июнь 7, 2021

In view of the new possibilities for treatment primary Sjögren's syndrome (pSS) given by availability biotechnological agents targeting various molecular and cellular actors pathological process disease, classification criteria aimed at selecting patients to be enrolled in therapeutic trials, validated outcome measures used as response these therapies, have been developed last decades. Unfortunately, trials so far completed with treatments yielded unsatisfactory or only partially positive results. The main issues that evoked justify poor results attempts are: (i) extreme variability disease phenotypes which are dependent on different underlying patterns biological mechanisms, (ii) fact has a long indolent course, most might already irreversible clinical features. advances research biomarkers can better distinguish diagnose an earlier phase also discussed.

Язык: Английский

---