-
Indian Journal of Nephrology 2024Hydroxychloroquine (HCQ) has immunomodulatory and immunosuppressive properties and is used in many rheumatological conditions like systemic lupus erythematosus,...
Hydroxychloroquine (HCQ) has immunomodulatory and immunosuppressive properties and is used in many rheumatological conditions like systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome. It is usually a widely used and well-tolerated DMARD (Disease Modifying Anti Rheumatic Drugs). Its most feared toxicities include retinopathy and, rarely, cardiomyopathy. Among its other reported side effects is drug-induced phospholipidosis. Here, we report two cases of HCQ-induced phospholipidosis based on renal biopsy electron microscopy. HCQ-induced phospholipidosis, although uncommon, must be considered as one of the differentials in a patient with persistent proteinuria.
PubMed: 38681001
DOI: 10.4103/ijn.ijn_325_22 -
Computers in Biology and Medicine Jun 2024Mitochondria are the metabolic hubs of cells, regulating energy production and antigen presentation, which are essential for activation, proliferation, and function of...
Identification of key mitochondria-related genes and their relevance to the immune system linking Parkinson's disease and primary Sjögren's syndrome through integrated bioinformatics analyses.
BACKGROUND
Mitochondria are the metabolic hubs of cells, regulating energy production and antigen presentation, which are essential for activation, proliferation, and function of immune cells. Recent evidence indicates that mitochondrial antigen presentation may have an impact on diseases such as Parkinson's disease (PD) and autoimmune diseases. However, there is limited knowledge about the mechanisms that regulate the presentation of mitochondrial antigens in these diseases.
METHODS
In the current study, RNA sequencing was performed on labial minor salivary gland (LSG) from 25 patients with primary Sjögren's syndrome (pSS) and 14 non-pSS aged controls. Additionally, we obtained gene expression omnibus datasets associated with PD patients from NCBI Gene Expression Omnibus (GEO) databases. Single-sample Gene Set Enrichment Analysis (ssGSEA), ESTIMATE and Spearman correlations were conducted to explore the association between mitochondrial related genes and the immune system. Furthermore, we applied weighted Gene Co-expression Network Analysis (WGCNA) to identify hub mitochondria-related genes and investigate the correlated networks in both diseases. Single cell transcriptome analysis, immunohistochemical (IHC) staining and quantitative real-time PCR (qRT-PCR) were used to verify the activation of the hub mitochondria-related pathway. Pearson correlations and the CIBERSORT algorithms were employed to further reveal the correlation between hub mitochondria-related pathways and immune infiltration.
RESULTS
The transcriptome analysis revealed the presence of overlapping mitochondria-related genes and mitochondrial DNA damage in patients with pSS and PD. Reactive oxygen species (ROS), the senescence marker p53, and the inflammatory markers CD45 and Bcl-2 were found to be regionally distributed in LSGs of pSS patients. WGCNA analysis identified the STING pathway as the central mitochondria-related pathway closely associated with the immune system. Single cell analysis, IHC staining, and qRT-PCR confirmed the activation of the STING pathway. Subsequent, bioinformatic analysis revealed the proportion of infiltrating immune cells in the STING-high and STING-low groups of pSS and PD. Furthermore, the study demonstrated the association of the STING pathway with innate and adaptive immune cells, as well as functional cells, in the immune microenvironment of PD and pSS.
CONCLUSION
Our study uncovered a central pathway that connects mitochondrial dysfunction and the immune microenvironment in PD and pSS, potentially offering valuable insights into therapeutic targets for these conditions.
Topics: Humans; Sjogren's Syndrome; Computational Biology; Parkinson Disease; Female; Mitochondria; Male; Middle Aged; Aged; Transcriptome; Gene Regulatory Networks; Genes, Mitochondrial
PubMed: 38677173
DOI: 10.1016/j.compbiomed.2024.108511 -
Pharmaceuticals (Basel, Switzerland) Mar 2024Systemic rheumatic diseases, including conditions such as rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, and systemic lupus erythematosus, represent a...
Systemic rheumatic diseases, including conditions such as rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, and systemic lupus erythematosus, represent a complex array of autoimmune disorders characterized by chronic inflammation and diverse clinical manifestations. This study focuses on unraveling the genetic underpinnings of these diseases by examining polymorphisms in key genes related to their pathology. Utilizing a comprehensive genetic analysis, we have documented the involvement of these genetic variations in the pathogenesis of rheumatic diseases. Our study has identified several key polymorphisms with notable implications in rheumatic diseases. Polymorphism at chr11_112020916 within the gene was prevalent across various conditions with a potential protective effect. Concurrently, the same gene polymorphism located at chr2_103010912, coding for the IL-18 receptor, was observed in most rheumatic conditions, reinforcing its potential protective role. Additionally, a further polymorphism in IL18R1 at chr2_103013408 seems to have a protective influence against the rheumatic diseases under investigation. In the context of emerging genes involved in rheumatic diseases, like , a significant polymorphism at chr6_161990516 was consistently identified across different conditions, exhibiting protective characteristics in these pathological contexts. The findings underscore the complexity of the genetic landscape in rheumatic autoimmune disorders and pave the way for a deeper understanding of their etiology and the possible development of more targeted and effective therapeutic strategies.
PubMed: 38675400
DOI: 10.3390/ph17040438 -
Korean Journal of Ophthalmology : KJO Jun 2024In the present study, we introduce human lacrimal gland imaging using an ultrasound biomicroscopy (UBM) with a soft cover and show their findings.
PURPOSE
In the present study, we introduce human lacrimal gland imaging using an ultrasound biomicroscopy (UBM) with a soft cover and show their findings.
METHODS
The representative UBM findings of palpebral lobes in seven subjects (four with non-Sjögren dry eye syndrome, one with Sjögren syndrome, and two healthy subjects) were described in this study. To prolapse the palpebral lobe, the examiner pulled the temporal part of the upper eyelid in the superotemporal direction and directed the subject to look in the inferonasal direction. We scanned the palpebral lobes longitudinally and transversely using UBM. We used an Aviso UBM with a 50 MHz linear probe and ClearScan.
RESULTS
In UBM of two healthy subjects, the echogenicity of the lacrimal gland was lower than that of the sclera and homogeneous. But the parenchyma of a patient with Sjögren dry eye syndrome was quite inhomogeneous compared to the healthy subjects. In two patients with dry eye syndrome, we were able to observe some lobules in the parenchyma. We could find excretory ducts running parallel at the surface of the longitudinal section in some subjects. In the longitudinal UBM scan of a subject, we observed a tubular structure at a depth of 1,500 μm that was considered a blood vessel. It ran from the superonasal to the inferotemporal direction. In a subject, we observed a large cyst beneath the conjunctiva.
CONCLUSIONS
Lacrimal gland imaging using UBM has both advantages of optical coherence tomography and sonography, and could be useful for evaluating dry eye syndrome.
Topics: Humans; Microscopy, Acoustic; Lacrimal Apparatus; Female; Male; Middle Aged; Adult; Dry Eye Syndromes; Aged; Sjogren's Syndrome
PubMed: 38665113
DOI: 10.3341/kjo.2023.0134 -
RMD Open Apr 2024Cardiovascular comorbidities are common in patients with autoimmune diseases. This study investigates the extent of subclinical atherosclerosis in patients with primary...
OBJECTIVES
Cardiovascular comorbidities are common in patients with autoimmune diseases. This study investigates the extent of subclinical atherosclerosis in patients with primary Sjögren's syndrome (pSS). Correlations with clinical factors such as organ involvement (OI) or disease activity were analysed and oxLDL antibodies (oxLDL ab) were measured as potential biomarkers of vascular damage.
METHODS
Patients with pSS were consecutively included from the rheumatology outpatient clinic. Age- and sex-matched controls were recruited (2:1 ratio). Data collection was performed by a standardised questionnaire and Doppler ultrasound to evaluate the plaque extent and carotid intima-media thickness (cIMT). Propensity score matching included all cardiovascular risk (CVR) factors and corresponding laboratory markers.
RESULTS
Data were available for 299 participants (199 pSS/100 controls), aged 59.4 years (50.6-65.0), 19.1% male. After matching, the pSS cohort had greater cIMT (p<0.001) and plaque extent (OR=1.82; 95% CI 1.14 to 2.95). Subgroup analyses of patients with pSS revealed that OI was associated with increased cIMT (p=0.025) and increased plaque occurrence compared with patients without OI (OR=1.74; 95% CI 1.02 to 3.01). OxLDL ab tended to be lower in patients with plaque (p=0.052). Correlations of higher Oxidized Low Density Lipoprotein (oxLDL) ab with EULAR Sjögren's Syndrome Disease Activity Index (p<0.001) and anti-Sjögren's-syndrome-related antigen A autoantibodies (SSA/Ro antibodies) (p=0.026) were observed.
CONCLUSIONS
Subclinical atherosclerosis occurs earlier and more severely in patients with pSS. The difference in cIMT between pSS and controls seems mainly driven by patients with OI, suggesting that this subgroup is particularly at risk. OxLDL ab might protect against atherosclerotic progression in patients with pSS. CVR stratification and preventive medications such as Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors should be discussed and further longitudinal studies are needed.
Topics: Humans; Sjogren's Syndrome; Male; Middle Aged; Female; Carotid Intima-Media Thickness; Atherosclerosis; Lipoproteins, LDL; Aged; Biomarkers; Case-Control Studies; Autoantibodies; Risk Factors; Plaque, Atherosclerotic
PubMed: 38663882
DOI: 10.1136/rmdopen-2023-003559 -
Expert Reviews in Molecular Medicine Apr 2024Autoimmune diseases are pathological autoimmune reactions in the body caused by various factors, which can lead to tissue damage and organ dysfunction. They can be... (Review)
Review
Autoimmune diseases are pathological autoimmune reactions in the body caused by various factors, which can lead to tissue damage and organ dysfunction. They can be divided into organ-specific and systemic autoimmune diseases. These diseases usually involve various body systems, including the blood, muscles, bones, joints and soft tissues. The transient receptor potential (TRP) and PIEZO receptors, which resulted in David Julius and Ardem Patapoutian winning the Nobel Prize in Physiology or Medicine in 2021, attracted people's attention. Most current studies on TRP and PIEZO receptors in autoimmune diseases have been carried out on animal model, only few clinical studies have been conducted. Therefore, this study aimed to review existing studies on TRP and PIEZO to understand the roles of these receptors in autoimmune diseases, which may help elucidate novel treatment strategies.
Topics: Humans; Autoimmune Diseases; Animals; Ion Channels; Transient Receptor Potential Channels
PubMed: 38659380
DOI: 10.1017/erm.2023.23 -
Experimental and Therapeutic Medicine Jun 2024Systemic lupus erythematosus (SLE) is an autoimmune disease which typically presents in young women. Patients with SLE exhibit features of accelerated atherosclerosis....
Systemic lupus erythematosus (SLE) is an autoimmune disease which typically presents in young women. Patients with SLE exhibit features of accelerated atherosclerosis. Here, the present study reported a rare case of acute myocardial infarction (AMI) in a male patient diagnosed with SLE. A 29-year-old male with no cardiovascular history was diagnosed with AMI and underwent coronary angiography, which showed a long-extended spiral-shaped dissection of the right coronary artery (RCA). The patient's autoimmune panel tested positive for antinuclear, anti-nuclear ribonucleoprotein/Smith and anti-Sjogren's syndrome A antibodies. The patient was diagnosed with SLE and was administered prednisone, hydroxychloroquine and calcium carbonate therapy. At the 3-month follow-up, a repeat coronary angiography showed no dissection in the RCA. Intravascular ultrasound and optical coherence tomography also showed an isolated atherosclerotic lesion without arterial dissection in the RCA. To the best of our knowledge, this is the first reported case of a male patient with SLE who developed myocardial infarction caused by spontaneous coronary artery dissection (SCAD). The present report may provide new insights into possible future treatments for SCAD. SCAD should be considered in patients with SLE and AMI, particularly in young patients without cardiovascular risk factors. Early diagnosis of SCAD is important to provide accurate therapy that differs from the treatment of AMI caused by atherosclerosis.
PubMed: 38655037
DOI: 10.3892/etm.2024.12534 -
Cancer Cell International Apr 2024Colon cancer ranks third among global tumours and second in cancer-related mortality, prompting an urgent need to explore new therapeutic targets. C6orf15 is a novel...
BACKGROUND
Colon cancer ranks third among global tumours and second in cancer-related mortality, prompting an urgent need to explore new therapeutic targets. C6orf15 is a novel gene that has been reported only in Sjogren's syndrome and systemic lupus erythematosus patients. We found a close correlation between increased C6orf15 expression and the occurrence of colon cancer. The aim of this study was to explore the potential of C6orf15 as a therapeutic target for colorectal cancer.
METHOD
RNA-seq differential expression analysis of the TCGA database was performed using the R package 'limma.' The correlation between target genes and survival as well as tumour analysis was analysed using GEPIA. Western blot and PCR were used to assess C6orf15 expression in colorectal cancer tissue samples. Immunofluorescence and immunohistochemistry were used to assess C6orf15 subcellular localization and tissue expression. The role of C6orf15 in liver metastasis progression was investigated via a mouse spleen infection liver metastasis model. The association of C6orf15 with signalling pathways was assessed using the GSEA-Hallmark database. Immunohistochemistry (IHC), qPCR and western blotting were performed to assess the expression of related mRNAs or proteins. Biological characteristics were evaluated through cell migration assays, MTT assays, and Seahorse XF96 analysis to monitor fatty acid metabolism.
RESULTS
C6orf15 was significantly associated with liver metastasis and survival in CRC patients as determined by the bioinformatic analysis and further verified by immunohistochemistry (IHC), qPCR and western blot results. The upregulation of C6orf15 expression in CRC cells can promote the nuclear translocation of β-catenin and cause an increase in downstream transcription. This leads to changes in the epithelial-mesenchymal transition (EMT) and alterations in fatty acid metabolism, which together promote liver metastasis of CRC.
CONCLUSION
Our study identified C6orf15 as a marker of liver metastasis in CRC. C6orf15 can activate the WNT/β-catenin signalling pathway to promote EMT and fatty acid metabolism in CRC.
PubMed: 38654238
DOI: 10.1186/s12935-024-03324-2 -
Arquivos de Neuro-psiquiatria Apr 2024Henrik and Torsten Sjögren (/'ʃoʊɡrən/ or SHOH-grən) were two Swedish physicians living in the same period, but completely unrelated, except for their notable...
Henrik and Torsten Sjögren (/'ʃoʊɡrən/ or SHOH-grən) were two Swedish physicians living in the same period, but completely unrelated, except for their notable contributions to Medicine. The first one described keratoconjunctivitis sicca, afterward called Sjögren's syndrome, and a fishing net aspect retinal pigmentation affecting visual acuity, nowadays known as Sjögren reticular dystrophy. The last one contributed to the understanding of Spielmeyer-Sjögren disease, Marinesco-Sjögren, and Sjögren-Larsson syndromes, all related to genetic disorders and neurological symptoms. In this paper, we aim to describe each disorder, in order to avoid any misunderstanding in diagnosis and for historical record.
Topics: Sjogren's Syndrome; Humans; Sweden; History, 19th Century; History, 20th Century
PubMed: 38653487
DOI: 10.1055/s-0044-1786022 -
Cureus Mar 2024Overlap syndrome is a clinical challenge and brings together a wide range of treatment options for the treating physician. Addressing each and every complaint of the...
Overlap syndrome is a clinical challenge and brings together a wide range of treatment options for the treating physician. Addressing each and every complaint of the patient is crucial. A 50-year-old female patient presented with skin thickening, blackening, and hyperkeratosis; dysphagia; joint pain; features of myopathy; Raynaud's phenomenon; and dry mouth. Inflammatory markers were raised along with a positive antinuclear antibody (ANA) with Golgi apparatus pattern, anti-Sjögren's-syndrome-related antigen A (anti-SSA)/Ro60 3+, anti-SSA/Ro52 3+, and anti-PM/Scl 2+ antibodies that suggested overlap syndrome. Although the patient had no respiratory complaints, a unique interstitial lung disease (ILD) pattern was noted during the evaluation. Skin manifestations were puzzling, but the histopathology analyses of skin biopsies taken from two different sites revealed distinguishing features of cutaneous lupus and dermatomyositis. Treatment with hydroxychloroquine, pilocarpine, nifedipine, methotrexate, and topical tacrolimus produced a dramatic improvement in the clinical features. This case highlights subtle and florid features of different autoimmune diseases. The hyperkeratotic skin changes were the most striking feature, but the whole evaluation process unveiled many rare presentations of known autoimmune conditions that can open doors to new areas of our understanding toward connective tissue diseases (CTDs). Our case report demonstrates significant heterogeneity in the ANA patterns, ILD patterns, clinical manifestations, and treatment approaches.
PubMed: 38646215
DOI: 10.7759/cureus.56531