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Serum bilirubin levels in primary Sjögren's syndrome: an association with interstitial lung disease.BMC Pulmonary Medicine Sep 2023We aimed to assess the association between serum bilirubin levels and interstitial lung disease (ILD) in patients with Primary Sjögren's syndrome (pSS).
OBJECTIVE
We aimed to assess the association between serum bilirubin levels and interstitial lung disease (ILD) in patients with Primary Sjögren's syndrome (pSS).
MATERIALS AND METHODS
The retrospectively analysis included 89 consecutive patients with pSS, we collected the clinical materials of pSS patients from the electronic medical records, and all pSS patients were divide into pSS with ILD group and pSS without ILD group.
RESULTS
Serum bilirubin levels were significantly lower in pSS patients with ILD than those without ILD (p = 0.010). Serum bilirubin levels showed a significant negative correlation with erythrocyte sedimentation rate (ESR) (r = -0.321, p = 0.002) in patients with pSS. A multivariable logistic regression analysis confirmed that serum bilirubin presented an independent association with ILD in patients with pSS (OR = 0.841, 95%CI:0.728-0.972, p = 0.019).
CONCLUSION
Serum bilirubin is independently associated with ILD and therefore may be a promising marker of ILD in patients with pSS.
Topics: Humans; Retrospective Studies; Sjogren's Syndrome; Lung Diseases, Interstitial; Electronic Health Records; Bilirubin
PubMed: 37777728
DOI: 10.1186/s12890-023-02672-5 -
Frontiers in Medicine 2023Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by exocrine and extra-glandular symptoms. The literature indicates that SS is an independent risk...
BACKGROUND
Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by exocrine and extra-glandular symptoms. The literature indicates that SS is an independent risk factor for atherosclerosis (AS); however, its pathophysiological mechanism remains undetermined. This investigation aimed to elucidate the crosstalk genes and pathways influencing the pathophysiology of SS and AS via bioinformatic analysis of microarray data.
METHODS
Microarray datasets of SS (GSE40611) and AS (GSE28829) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were acquired using R software's "limma" packages, and the functions of common DEGs were determined using Gene Ontology and Kyoto Encyclopedia analyses. The protein-protein interaction (PPI) was established using the STRING database. The hub genes were assessed via cytoHubba plug-in and validated by external validation datasets (GSE84844 for SS; GSE43292 for AS). Gene set enrichment analysis (GSEA) and immune infiltration of hub genes were also conducted.
RESULTS
Eight 8 hub genes were identified using the intersection of four topological algorithms in the PPI network. Four genes (CTSS, IRF8, CYBB, and PTPRC) were then verified as important cross-talk genes between AS and SS with an area under the curve (AUC) ≥0.7. Furthermore, the immune infiltration analysis revealed that lymphocytes and macrophages are essentially linked with the pathogenesis of AS and SS. Moreover, the shared genes were enriched in multiple metabolisms and autoimmune disease-related pathways, as evidenced by GSEA analyses.
CONCLUSION
This is the first study to explore the common mechanism between SS and AS. Four key genes, including CTSS, CYBB, IRF8, and PTPRC, were associated with the pathogenesis of SS and AS. These hub genes and their correlation with immune cells could be a potential diagnostic and therapeutic target.
PubMed: 37727764
DOI: 10.3389/fmed.2023.1185303 -
RMD Open Aug 2023To assess to what extent leflunomide (LEF) and hydroxychloroquine (HCQ) therapy in patients with primary Sjögren's syndrome (RepurpSS-I) targets type I IFN-associated...
Leflunomide/hydroxychloroquine combination therapy targets type I IFN-associated proteins in patients with Sjögren's syndrome that show potential to predict and monitor clinical response.
OBJECTIVES
To assess to what extent leflunomide (LEF) and hydroxychloroquine (HCQ) therapy in patients with primary Sjögren's syndrome (RepurpSS-I) targets type I IFN-associated responses and to study the potential of several interferon associated RNA-based and protein-based biomarkers to predict and monitor treatment.
METHODS
In 21 patients treated with LEF/HCQ and 8 patients treated with placebo, blood was drawn at baseline, 8, 16 and 24 weeks. IFN-signatures based on RNA expression of five IFN-associated genes were quantified in circulating mononuclear cells and in whole blood. MxA protein levels were measured in whole blood, and protein levels of CXCL10 and Galectin-9 were quantified in serum. Differences between responders and non-responders were assessed and receiver operating characteristic analysis was used to determine the capacity of baseline expression and early changes (after 8 weeks of treatment) in biomarkers to predict treatment response at the clinical endpoint.
RESULTS
IFN-signatures in peripheral blood mononuclear cell and whole blood decreased after 24 weeks of LEF/HCQ treatment, however, changes in IFN signatures only poorly correlated with changes in disease activity. In contrast to baseline IFN signatures, baseline protein concentrations of galectin-9 and decreases in circulating MxA and Galectin-9 were robustly associated with clinical response. Early changes in serum Galectin-9 best predicted clinical response at 24 weeks (area under the curve 0.90).
CONCLUSIONS
LEF/HCQ combination therapy targets type-I IFN-associated proteins that are associated with strongly decreased B cell hyperactivity and disease activity. IFN-associated Galectin-9 is a promising biomarker for treatment prediction and monitoring in pSS patients treated with LEF/HCQ.
Topics: Humans; Biomarkers; Hydroxychloroquine; Interferon Type I; Leflunomide; Leukocytes, Mononuclear; Proteins; RNA; Sjogren's Syndrome
PubMed: 37532471
DOI: 10.1136/rmdopen-2023-002979 -
Frontiers in Immunology 2023Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to... (Review)
Review
Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modifying antirheumatic drug, iguratimod has pharmacological activities such as regulating autoimmune disorders, inflammatory cytokines, regulating immune cell activation, differentiation and proliferation, improving bone metabolism, and inhibiting fibrosis. In recent years, clinical studies have found that iguratimod is effective in the treatment of RA, SLE, IGG4-RD, Sjogren 's syndrome, ankylosing spondylitis, interstitial lung disease, and other autoimmune diseases and rheumatic diseases. The amount of basic and clinical research on other autoimmune diseases is also increasing. Therefore, this review systematically reviews the latest relevant literature in recent years, reviews the research results in recent years, and summarizes the research progress of iguratimod in the treatment of related diseases. This review highlights the role of iguratimod in the protection of autoimmune and rheumatic bone and related immune diseases. It is believed that iguratimod's unique mode of action and its favorable patient response compared to other DMARDs make it a suitable antirheumatic and bone protective agent in the future.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Chromones; Sjogren's Syndrome; Cytokines
PubMed: 37809072
DOI: 10.3389/fimmu.2023.1150661 -
Clinical and Experimental Rheumatology Dec 2023Recent studies have implicated cytotoxic CD4 and CD8 T cells in primary Sjögren's syndrome (pSS) and IgG4-related disease (IgG4-RD), but their association with immune...
OBJECTIVES
Recent studies have implicated cytotoxic CD4 and CD8 T cells in primary Sjögren's syndrome (pSS) and IgG4-related disease (IgG4-RD), but their association with immune aging and organ-specific clinical features remain unclear. CX3CR1 is expressed on cytotoxic CD4 and CD8 T cells. The aim of this study was to determine associations of peripheral CX3CR1+CD4 and CX3CR1+CD8 T cells with aging and clinical features.
METHODS
Whole blood samples were freshly obtained from consecutive patients with active, treatment-naïve pSS (n=57), IgG4-RD (n=54), and healthy individuals (n=40) and analysed by flow cytometry for CX3CR1+CD4 and CX3CR1+CD8 proportions. Associations of those T cells with aging and clinical features were determined.
RESULTS
CX3CR1+CD4 and CX3CR1+CD8 T cells selectively expressed perforin and granzyme B. Proportions of CX3CR1+CD4 and CX3CR1+CD8 T cells were significantly higher in pSS and IgG4-RD than in healthy individuals. Higher proportions of CX3CR1+CD8 T cells were associated with aging in pSS and IgG4-RD but not in healthy individuals. Sex differences were not associated with proportions of CX3CR1+CD8 T cells. Furthermore, patients with pSS with interstitial lung disease showed higher proportions of CX3CR1+CD8 T cells than those without interstitial lung disease. IgG4-RD patients with retroperitoneal fibrosis and/or aortitis exhibited higher proportions of CX3CR1+CD8 T cells compared with those with Mikulicz's disease. Moreover, proportions of CX3CR1+CD8 T cells were decreased following glucocorticoid treatment in paralleled with clinical improvements in IgG4-RD.
CONCLUSIONS
CX3CR1+CD8 T cells might be involved in immune aging and distinct clinical phenotypes of patients with pSS or IgG4-RD.
Topics: Humans; Male; Female; Sjogren's Syndrome; Immunoglobulin G4-Related Disease; CD8-Positive T-Lymphocytes; Aging; Lung Diseases, Interstitial; CX3C Chemokine Receptor 1
PubMed: 37812481
DOI: 10.55563/clinexprheumatol/kfsd65 -
BMC Pulmonary Medicine Nov 2023We report a rare case of Sjogren's syndrome complicated with Birt-Hogg-Dubé syndrome (BHDS) not previously mentioned in the literature. Further, there is insufficient... (Review)
Review
We report a rare case of Sjogren's syndrome complicated with Birt-Hogg-Dubé syndrome (BHDS) not previously mentioned in the literature. Further, there is insufficient evidence linking the two diseases. Here, we review existing diagnostic algorithms for diagnosing diffuse cystic lung disease and provide new insights. The patient initially complained of thirst and dry eyes for ten years, and gradually developed shortness of breath. After admission, physical examination showed five missing teeth, decreased respiratory sounds in both lower lungs, and Velcro rales. Computed tomography showed multiple thin-walled cystic lesions in both lungs. Initial xerophthalmia and labial gland biopsy seemed to reveal a pulmonary cystic change associated with Sjogren's syndrome. Before discharge, a rash suspected to indicate a fibrofollicular tumor in the neck was observed, and then FLCN variant has been found. The challenges how to clarify the diagnosis of DCLD causes are discussed.
Topics: Humans; Birt-Hogg-Dube Syndrome; Sjogren's Syndrome; Lung Diseases; Lung; Cysts
PubMed: 37993820
DOI: 10.1186/s12890-023-02680-5 -
International Journal of Molecular... May 2024Sjögren's Disease (SjD) is an autoimmune disease of the exocrine tissues. Etiological events result in the loss of epithelial homeostasis alongside extracellular matrix... (Review)
Review
Sjögren's Disease (SjD) is an autoimmune disease of the exocrine tissues. Etiological events result in the loss of epithelial homeostasis alongside extracellular matrix (ECM) destruction within the salivary and lacrimal glands, followed by immune cell infiltration. In this review, we have assessed the current understanding of epithelial-mesenchymal transition (EMT)-associated changes within the salivary epithelium potentially involved in salivary dysfunction and SjD pathogenesis. We performed a PubMed literature review pertaining to the determination of pathogenic events that lead to EMT-related epithelial dysfunction and signaling in SjD. Molecular patterns of epithelial dysfunction in SjD salivary glands share commonalities with EMT mediating wound healing. Pathological changes altering salivary gland integrity and function may precede direct immune involvement while perpetuating MMP9-mediated ECM destruction, inflammatory mediator expression, and eventual immune cell infiltration. Dysregulation of EMT-associated factors is present in the salivary epithelium of SjD and may be significant in initiating and perpetuating the disease. In this review, we further highlight the gap regarding mechanisms that drive epithelial dysfunction in salivary glands in the early or subclinical pre-lymphocytic infiltration stages of SjD.
Topics: Humans; Sjogren's Syndrome; Epithelial-Mesenchymal Transition; Salivary Glands; Animals; Epithelium; Epithelial Cells; Signal Transduction; Extracellular Matrix
PubMed: 38732189
DOI: 10.3390/ijms25094973 -
Frontiers in Pharmacology 2023To evaluate efficacy and safety of iguratimod (IGU) in the treatment of rheumatic and autoimmune diseases. Databases such as Pubmed, Embase, Sinomed were searched (as...
To evaluate efficacy and safety of iguratimod (IGU) in the treatment of rheumatic and autoimmune diseases. Databases such as Pubmed, Embase, Sinomed were searched (as of July 2022) to collect randomized controlled trials (RCTs) of IGU in the treatment of rheumatic and autoimmune diseases. Two researchers independently screened the literature, extracted data, assessed the risk of bias of the included literature, and performed meta-analysis using RevMan 5.4 software. A total of 84 RCTs and 4 types of rheumatic and autoimmune diseases [rheumatoid arthritis (RA), ankylosing spondylitis (AS), primary Sjögren's syndrome (PSS) and Autoimmune disease with interstitial pneumonia]. Forty-three RCTs reported RA and showed that IGU + MTX therapy can improve ACR20 (RR 1.45 [1.14, 1.84], = 0.003), ACR50 (RR 1.80 [1.43, 2.26], < 0.0000), ACR70 (RR 1.84 [1.27, 2.67], = 0.001), DAS28 (WMD -1.11 [-1.69, -0.52], = 0.0002), reduce ESR (WMD -11.05 [-14.58, -7.51], < 0.00001), CRP (SMD -1.52 [-2.02, -1.02], < 0.00001), RF (SMD -1.65 [-2.48, -0.82], < 0.0001), and have a lower incidence of adverse events (RR 0.84 [0.78, 0.91], < 0.00001) than the control group. Nine RCTs reported AS and showed that IGU can decrease the BASDAI score (SMD -1.62 [-2.20, -1.05], < 0.00001), BASFI score (WMD -1.07 [-1.39, -0.75], < 0.00001), VAS (WMD -2.01 [-2.83, -1.19], < 0.00001), inflammation levels (decreasing ESR, CRP and TNF-α). Thirty-two RCTs reported PSS and showed that IGU can reduce the ESSPRI score (IGU + other therapy group: WMD -1.71 [-2.44, -0.98], < 0.00001; IGU only group: WMD -2.10 [-2.40, -1.81], < 0.00001) and ESSDAI score (IGU + other therapy group: WMD -1.62 [-2.30, -0.94], < 0.00001; IGU only group: WMD -1.51 [-1.65, -1.37], < 0.00001), inhibit the inflammation factors (reduce ESR, CRP and RF) and increase Schirmer's test score (IGU + other therapy group: WMD 2.18 [1.76, 2.59], < 0.00001; IGU only group: WMD 1.55 [0.35, 2.75], = 0.01); The incidence of adverse events in IGU group was also lower than that in control group (IGU only group: RR 0.66 [0.48, 0.98], = 0.01). Three RCTs reported Autoimmune disease with interstitial pneumonia and showed that IGU may improve lung function. Based on current evidence, IGU may be a safe and effective therapy for RA, AS, PSS and autoimmune diseases with interstitial pneumonia. : (CRD42021289489).
PubMed: 38143490
DOI: 10.3389/fphar.2023.1189142 -
Biomolecules Jan 2024Sjögren's syndrome dry eye (SSDE) is a subset of Sjögren's syndrome marked by dry eye symptoms that is distinct from non-Sjögren's syndrome dry eye (NSSDE). As SSDE... (Review)
Review
Sjögren's syndrome dry eye (SSDE) is a subset of Sjögren's syndrome marked by dry eye symptoms that is distinct from non-Sjögren's syndrome dry eye (NSSDE). As SSDE can lead to severe complications, its early detection is imperative. However, the differentiation between SSDE and NSSDE remains challenging due to overlapping clinical manifestations. This review endeavors to give a concise overview of the classification, pathophysiology, clinical features and presentation, ocular and systemic complications, clinical diagnosis, and management of SSDE. Despite advancements, limitations in current diagnostic methods underscore the need for novel diagnostic modalities. Thus, the current review examines various diagnostic biomarkers utilized for SSDE identification, encompassing serum, salivary, and tear analyses. Recent advancements in proteomic research and exosomal biomarkers offer promising diagnostic potential. Through a comprehensive literature review spanning from 2016 to 2023, we highlight molecular insights and advanced diagnostic modalities that have the potential to enhance our understanding and diagnosis of SSDE.
Topics: Humans; Sjogren's Syndrome; Proteomics; Dry Eye Syndromes; Eye; Biomarkers
PubMed: 38254680
DOI: 10.3390/biom14010080 -
Scientific Reports Oct 2023There are limited large population-based cohort studies on the risk of incident autoimmune diseases among patients with newly diagnosed psoriatic disease. The objective...
There are limited large population-based cohort studies on the risk of incident autoimmune diseases among patients with newly diagnosed psoriatic disease. The objective of this study was to assess the risk of autoimmune diseases in patients with newly diagnosed psoriatic disease. Using the Korean National Health Insurance Service database, patients with newly diagnosed psoriatic disease between 2007 and 2019 were included. Comparators were randomly selected and matched according to age and sex. A total of 321,354 patients with psoriatic disease and 321,354 matched comparators were included in this study. Patients with psoriatic disease had a significantly higher risk of Crohn's disease [adjusted hazard ratio (aHR), 1.95; 95% confidence interval (CI) 1.42-2.67], ulcerative colitis (aHR, 1.65; 95% CI 1.39-1.96), systemic lupus erythematosus (aHR, 1.86; 95% CI 1.34-2.57), rheumatoid arthritis (aHR, 1.63; 95% CI 1.52-1.76), ankylosing spondylitis (aHR, 2.32; 95% CI 1.95-2.77), alopecia areata (aHR, 1.41; 95% CI 1.35-1.46), and type 1 diabetes (aHR, 1.23; 95% CI 1.11-1.37). However, the risk of Graves' disease, Hashimoto's disease, Sjögren's syndrome, and systemic sclerosis was not significantly different between the groups. In conclusion, patients with newly diagnosed psoriatic disease may have a significantly increased risk of incident autoimmune diseases.
Topics: Humans; Autoimmune Diseases; Arthritis, Rheumatoid; Spondylitis, Ankylosing; Graves Disease; Hashimoto Disease; Risk Factors; Incidence
PubMed: 37798369
DOI: 10.1038/s41598-023-43778-4