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Investigative Ophthalmology & Visual... Aug 2023We investigated the therapeutic effect of recombinant thymosin β4 (rTβ4) on rabbit autoimmune dacryoadenitis, an animal model of SS dry eye, and explore its mechanisms.
PURPOSE
We investigated the therapeutic effect of recombinant thymosin β4 (rTβ4) on rabbit autoimmune dacryoadenitis, an animal model of SS dry eye, and explore its mechanisms.
METHODS
Rabbits were treated topically with rTβ4 or PBS solution after disease onset for 28 days, and clinical scores were determined by assessing tear secretion, break-up time, fluorescein, hematoxylin and eosin staining, and periodic acid-Schiff. The expression of inflammatory mediators in the lacrimal glands were measured by real-time PCR. The expression of T helper 17 (Th17) cell-related transcription factors and cytokines were detected by real-time PCR and Western blotting. The molecular mechanism underlying the effects of rTβ4 on Th17 cell responses was investigated by Western blotting.
RESULTS
Topical administration of rTβ4 after disease onset efficiently ameliorated the ocular surface inflammation and relieved the clinical symptoms. Further analysis revealed that rTβ4 treatment significantly inhibited the expression of Th17-related genes (RORC, IL-17A, IL-17F, IL-1R1, IL-23R, and granulocyte-macrophage colony-stimulating factor) and IL-17 protein in lacrimal glands, and meanwhile decreased the inflammatory mediators expression. Mechanistically, we demonstrated that rTβ4 repressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3) both in vivo and in vitro. Activation of the STAT3 signal pathway by Colivelin partly reversed the suppressive effects of rTβ4 on IL-17 expression in vitro.
CONCLUSIONS
rTβ4 could alleviate ongoing autoimmune dacryoadenitis in rabbits, probably by suppressing Th17 response via partly affecting the STAT3 pathway. These data may provide a new insight into the therapeutic effect and mechanism of rTβ4 in dry eye associated with Sjögren's syndrome.
Topics: Animals; Rabbits; Interleukin-17; Tears; Th17 Cells; Dacryocystitis; Dry Eye Syndromes; Disease Models, Animal
PubMed: 37531112
DOI: 10.1167/iovs.64.11.3 -
MedRxiv : the Preprint Server For... Jan 2024To examine whether genetically predicted susceptibility to ten autoimmune diseases (Behçet's disease, coeliac disease, dermatitis herpetiformis, lupus, psoriasis,...
OBJECTIVE
To examine whether genetically predicted susceptibility to ten autoimmune diseases (Behçet's disease, coeliac disease, dermatitis herpetiformis, lupus, psoriasis, rheumatoid arthritis, sarcoidosis, Sjögren's syndrome, systemic sclerosis, and type 1 diabetes) is associated with risk of non-Hodgkin lymphoma (NHL).
DESIGN
Two sample Mendelian randomization (MR) study.
SETTING
Genome wide association studies (GWASs) of ten autoimmune diseases, NHL, and four NHL subtypes (i.e., follicular lymphoma, mature T/natural killer-cell lymphomas, non-follicular lymphoma, and other and unspecified types of NHL).
ANALYSIS
We used data from the largest publicly available GWASs of European ancestry for each autoimmune disease, NHL, and NHL subtypes. For each autoimmune disease, we extracted single nucleotide polymorphisms (SNPs) strongly associated ( < 5×10) with that disease and that were independent of one another (R < 1×10) as genetic instruments. SNPs within the human leukocyte antigen region were not considered due to potential pleiotropy. Our primary MR analysis was the inverse-variance weighted analysis. Additionally, we conducted MR-Egger, weighted mode, and weighted median regression to address potential bias due to pleiotropy, and robust adjusted profile scores to address weak instrument bias. We carried out sensitivity analysis limited to the non-immune pathway for nominally significant findings. To account for multiple testing, we set the thresholds for statistical significance at < 5×10.
PARTICIPANTS
The number of cases and controls identified in the relevant GWASs were 437 and 3,325 for Behçet's disease, 4,918 and 5,684 for coeliac disease, 435 and 341,188 for dermatitis herpetiformis, 4,576 and 8,039 for lupus, 11,988 and 275,335 for psoriasis, 22,350 and 74,823 for rheumatoid arthritis, 3,597 and 337,121 for sarcoidosis, 2,735 and 332,115 for Sjögren's syndrome, 9,095 and 17,584 for systemic sclerosis, 18,942 and 501,638 for type 1 diabetes, 2,400 and 410,350 for NHL; and 296 to 2,340 cases and 271,463 controls for NHL subtypes.
EXPOSURES
Genetic variants predicting ten autoimmune diseases: Behçet's disease, coeliac disease, dermatitis herpetiformis, lupus, psoriasis, rheumatoid arthritis, sarcoidosis, Sjögren's syndrome, systemic sclerosis, and type 1 diabetes.
MAIN OUTCOME MEASURES
Estimated associations between genetically predicted susceptibility to ten autoimmune diseases and the risk of NHL.
RESULTS
The variance of each autoimmune disease explained by the SNPs ranged from 0.3% to 3.1%. Negative associations between type 1 diabetes and sarcoidosis and the risk of NHL were observed (odds ratio [OR] 0.95, 95% confidence interval [CI]: 0.92 to 0.98, = 5×10, and OR 0.92, 95% CI: 0.85 to 0.99, = 2.8×10, respectively). These findings were supported by the sensitivity analyses accounting for potential pleiotropy and weak instrument bias. No significant associations were found between the other eight autoimmune diseases and NHL risk. Of the NHL subtypes, type 1 diabetes was most strongly associated with follicular lymphoma (OR 0.91, 95% CI: 0.86 to 0.96, = 1×10), while sarcoidosis was most strongly associated with other and unspecified NHL (OR 0.86, 95% CI: 0.75 to 0.97, = 1.8×10).
CONCLUSIONS
These findings suggest that genetically predicted susceptibility to type 1 diabetes, and to some extent sarcoidosis, might reduce the risk of NHL. However, future studies with different datasets, approaches, and populations are warranted to further examine the potential associations between these autoimmune diseases and the risk of NHL.
PubMed: 38343812
DOI: 10.1101/2024.01.20.24301459 -
Journal of Traditional Chinese Medicine... Aug 2023To investigate the possible mechanism underlying the effect of the Lushi Runzao decoction on Sjogren's syndrome using network pharmacology and to verify the...
OBJECTIVE
To investigate the possible mechanism underlying the effect of the Lushi Runzao decoction on Sjogren's syndrome using network pharmacology and to verify the mechanismsanimal experiments.
METHODS
Available biological data on each drug in the Lushi Runzao decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the target proteins of Sjogren's syndrome were retrieved from the GeneCards database. Information regarding Sjogren's syndrome and the targets of the drugs were compared to obtain overlapping elements. This information was imported into the STRING platform to obtain a protein-protein interaction network diagram, following which a "component-target" network diagram was constructed using screened drug components and target informationCytoscape software. The database for annotation, visualization, and integrated discovery was used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways analyses. Pathway information predicted by network pharmacology was verified using animal experiments.
RESULTS
The Lushi Runzao decoction ameliorated Sjogren's syndrome mainly by influencing tumor necrosis factor as well as certain cytokines and chemokines. The decoction also influenced the interleukin-17 and advanced glycosylation end products (AGE)-receptor for AGE signaling pathways.
CONCLUSION
The Lushi Runzao decoction ameliorates Sjogren's syndromemultiple targets and multiple signaling pathways. Network pharmacology is useful for making a comprehensive prediction regarding the efficacy of the Lushi Runzao decoction, and this information may be helpful in clinical research.
Topics: Animals; Network Pharmacology; Sjogren's Syndrome; Cytokines; Databases, Factual; Glycation End Products, Advanced; Medicine, Chinese Traditional; Drugs, Chinese Herbal
PubMed: 37454260
DOI: 10.19852/j.cnki.jtcm.2023.04.004 -
Clinical and Experimental Rheumatology Dec 2023Primary Sjögren's syndrome (pSS) is frequently associated with autoimmune thyroiditis (AT). The aim of this study was to evaluate the prevalence of AT in a national...
OBJECTIVES
Primary Sjögren's syndrome (pSS) is frequently associated with autoimmune thyroiditis (AT). The aim of this study was to evaluate the prevalence of AT in a national cohort of pSS and to describe the clinical and histological phenotype of patients with pSS and associated AT.
METHODS
In this multicentre cross-sectional study, data from 2546 pSS were collected and the presence of AT was reported. In a subgroup, the histology of minor salivary glands was evaluated. Differences between pSS with and without AT were evaluated.
RESULTS
A concomitant pSS and AT was detected in 19.6% of cases. Patients with pSS and AT displayed a lower prevalence of lymphoma, male sex and disease-modifying anti-rheumatic drugs (DMARDs) use and a higher prevalence of fibromyalgia, coeliac disease and hypergammaglobulinaemia. Multivariable analysis confirmed a higher prevalence of fibromyalgia and coeliac disease and lower use of DMARDs. In a subgroup of patients (n=232), a significantly higher focus score and number of foci was detected in pSS without AT (n=169) as compared to pSS with AT (n=54).
CONCLUSIONS
This is the largest study evaluating the coexistence of pSS and AT. We confirm a high association between pSS and AT and describe the presence of a different phenotype characterized by a higher rate of celiac disease and fibromyalgia. Although not significant, the lower prevalence of both lymphoma and intake of DMARDs, along with a significantly lower focus score and number of foci, possibly suggest a more favourable outcome in concomitant pSS and AT which further deserve future investigations.
Topics: Humans; Male; Sjogren's Syndrome; Cross-Sectional Studies; Fibromyalgia; Celiac Disease; Thyroiditis, Autoimmune; Antirheumatic Agents; Lymphoma
PubMed: 38149510
DOI: 10.55563/clinexprheumatol/eh36vs -
Immunology Letters Aug 2023Plasma cells are the antibody secretors of the immune system. Continuous antibody secretion over years can provide long-term immune protection but could also be held...
Plasma cells are the antibody secretors of the immune system. Continuous antibody secretion over years can provide long-term immune protection but could also be held responsible for long-lasting autoimmunity in case of self-reactive plasma cells. Systemic autoimmune rheumatic diseases (ARD) affect multiple organ systems and are associated with a plethora of different autoantibodies. Two prototypic systemic ARDs are systemic lupus erythematosus (SLE) and Sjögren's disease (SjD). Both diseases are characterized by B-cell hyperactivity and the production of autoantibodies against nuclear antigens. Analogues to other immune cells, different subsets of plasma cells have been described. Plasma cell subsets are often defined dependent on their current state of maturation, that also depend on the precursor B-cell subset from which they derived. But, a universal definition of plasma cell subsets is not available so far. Furthermore, the ability for long-term survival and effector functions may differ, potentially in a disease-specific manner. Characterization of plasma cell subsets and their specificity in individual patients can help to choose a suitable targeting approach for either a broad or more selective plasma cell depletion. Targeting plasma cells in systemic ARDs is currently challenging because of side effects or varying depletion efficacies in the tissue. Recent developments, however, like antigen-specific targeting and CAR-T-cell therapy might open up major benefits for patients beyond current treatment options.
Topics: Humans; Plasma Cells; Autoimmunity; Autoantibodies; Lupus Erythematosus, Systemic; Sjogren's Syndrome; Respiratory Distress Syndrome; Autoimmune Diseases
PubMed: 37315847
DOI: 10.1016/j.imlet.2023.06.005 -
Rheumatology and Immunology Research Mar 2024In Sjögren's Syndrome (SS), clinical heterogeneity and discordance between disease activity measures and patient experience are key obstacles to effective therapeutic... (Review)
Review
In Sjögren's Syndrome (SS), clinical heterogeneity and discordance between disease activity measures and patient experience are key obstacles to effective therapeutic development. Patient reported outcome measures (PROMs) are useful tools for understanding the unmet needs from the patients' perspective and therefore they are key for the development of patient centric healthcare systems. Initial concern about the subjectivity of PROMs has given way to methodological rigour and clear guidance for the development of PROMs. To date, several studies of patient stratification using PROMs have identified similar symptom-based subgroups. There is evidence to suggest that these subgroups may represent different disease endotypes with differing responses to therapeutic interventions. Stratified medicine approaches, alongside sensitive outcome measures, have the potential to improve our understanding of SS pathobiology and therapeutic development. The inclusion of PROMs is important for the success of such approaches. In this review we discuss the opportunities of using PROMs in understanding the pathogenesis of and therapeutic development for SS.
PubMed: 38571930
DOI: 10.1515/rir-2024-0004 -
Viruses Jan 2024Alzheimer's disease and Parkinson's disease represent the most common forms of cognitive impairment. Multiple sclerosis is a chronic inflammatory disease of the central... (Review)
Review
Alzheimer's disease and Parkinson's disease represent the most common forms of cognitive impairment. Multiple sclerosis is a chronic inflammatory disease of the central nervous system responsible for severe disability. An aberrant immune response is the cause of myelin destruction that covers axons in the brain, spinal cord, and optic nerves. Systemic lupus erythematosus is an autoimmune disease characterized by alteration of B cell activation, while Sjögren's syndrome is a heterogeneous autoimmune disease characterized by altered immune responses. The etiology of all these diseases is very complex, including an interrelationship between genetic factors, principally immune associated genes, and environmental factors such as infectious agents. However, neurodegenerative and autoimmune diseases share proinflammatory signatures and a perturbation of adaptive immunity that might be influenced by herpesviruses. Therefore, they might play a critical role in the disease pathogenesis. The aim of this review was to summarize the principal findings that link herpesviruses to both neurodegenerative and autoimmune diseases; moreover, briefly underlining the potential therapeutic approach of virus vaccination and antivirals.
Topics: Humans; Autoimmune Diseases; Herpesviridae; Neurodegenerative Diseases; Multiple Sclerosis; Sjogren's Syndrome
PubMed: 38257833
DOI: 10.3390/v16010133 -
Journal of Clinical Medicine May 2024Depressive disorders are a growing problem worldwide. They are also characterized by high comorbidity, including from the circle of dermatological diseases. Autoimmune... (Review)
Review
Depressive disorders are a growing problem worldwide. They are also characterized by high comorbidity, including from the circle of dermatological diseases. Autoimmune diseases seem to be particularly correlated with depressive comorbidity, raising the question of their possible common pathomechanism. The PubMed database was searched, focusing on results published after 2016. A particular reciprocal correlation of depressive disorders with psoriasis, atopic dermatitis, alopecia areata, impetigo, lupus and systemic scleroderma was found. One possible explanation for the co-occurrence of the above diseases is that the inflammatory theory may be applicable to depression, the various elements of which also apply to autoimmune diseases.
PubMed: 38892934
DOI: 10.3390/jcm13113224 -
Rheumatology (Oxford, England) Oct 2023To assess the usefulness of [18F]-fluorodeoxyglucose (FDG)-PET/CT (i) to discriminate between primary SS (pSS) patients with and without lymphomas and (ii) to evaluate...
OBJECTIVES
To assess the usefulness of [18F]-fluorodeoxyglucose (FDG)-PET/CT (i) to discriminate between primary SS (pSS) patients with and without lymphomas and (ii) to evaluate systemic disease activity in pSS.
METHODS
ACR-EULAR-positive pSS patients who underwent FDG-PET/CT were included. Scans were visually evaluated and quantitative analysis was performed by measuring standardized uptake values (SUV) of salivary and lacrimal glands and systemic regions. Receiver operating characteristic curve analyses were performed to find SUV cut-off values to discriminate between lymphoma and non-lymphoma.
RESULTS
Of the 70 included patients, 26 were diagnosed with a pSS-associated lymphoma, mostly of the mucosa-associated lymphoid tissue type (23/26). Lymphoma patients showed higher FDG uptake in the parotid and submandibular glands, and more frequently showed presence of nodular lung lesions, compared with non-lymphoma patients. The accuracy of the maximum SUV (SUVmax) in the parotid and submandibular gland to predict lymphoma diagnosis was good, with optimal cut-off points of 3.1 and 2.9. After combining these three visual and quantitative findings (nodular lung lesions, parotid SUVmax > 3.1 and submandibular SUVmax > 2.9), sensitivity was 92% when at least one of the three features were present, and specificity was 91% in case at least two features were present. Furthermore, FDG-PET/CT was able to detect systemic manifestations in pSS patients, mostly involving lymph nodes, entheses and lungs.
CONCLUSIONS
FDG-PET/CT can assist in excluding pSS-associated lymphomas in patients without PET abnormalities, possibly leading to a decrease of invasive biopsies in suspected lymphoma patients. Furthermore, FDG-PET/CT is able to detect systemic manifestations in pSS and can guide to the best biopsy location.
Topics: Humans; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Sjogren's Syndrome; Positron-Emission Tomography; Lymphoma, B-Cell, Marginal Zone; Radiopharmaceuticals
PubMed: 36759907
DOI: 10.1093/rheumatology/kead071 -
BMC Medicine Mar 2024There is a high prevalence of autoimmune conditions in women specially in the reproductive years; thus, the association with adverse pregnancy outcomes has been widely...
BACKGROUND
There is a high prevalence of autoimmune conditions in women specially in the reproductive years; thus, the association with adverse pregnancy outcomes has been widely studied. However, few autoimmune conditions/adverse outcomes have been studied more than others, and this umbrella review aims to consolidate existing knowledge in this area with the aim to provide new knowledge and also identify gaps in this research area.
METHODS
Medline, Embase, and Cochrane databases were searched from inception to December 2023. Screening, data extraction, and quality appraisal (AMSTAR 2) were done by two independent reviewers. Data were synthesised narratively and quantitatively. Relative risks (RR)/odds ratio (OR) with 95% confidence intervals were reported.
RESULTS
Thirty-two reviews were included consisting of 709 primary studies. The review reported the association between 12 autoimmune conditions and 16 adverse pregnancy outcomes. Higher risk of miscarriage is reported in women with Sjögren's syndrome RR 8.85 (95% CI 3.10-25.26) and systemic lupus erythematosus (SLE) OR 4.90 (3.10-7.69). Pre-eclampsia was reported higher in women with type 1 diabetes mellitus (T1DM) OR 4.19 (3.08-5.71) and SLE OR 3.20 (2.54-4.20). Women reported higher risk of diabetes during pregnancy with inflammatory bowel disease (IBD) OR 2.96 (1.47-5.98). There was an increased risk of intrauterine growth restriction in women with systemic sclerosis OR 3.20 (2.21-4.53) and coeliac disease OR 1.71 (1.36-2.14). Preterm birth was associated with T1DM OR 4.36 (3.72-5.12) and SLE OR 2.79 (2.07-3.77). Low birth weight babies were reported in women with women with SLE or systemic sclerosis OR 5.95 (4.54-7.80) and OR 3.80 (2.16-6.56), respectively. There was a higher risk of stillbirth in women with T1DM OR 3.97 (3.44-4.58), IBD OR 1.57 (1.03-2.38), and coeliac disease OR 1.57 (1.17-2.10). T1DM in women was associated with 32% lower odds of small for gestational age baby OR 0.68 (0.56-0.83).
CONCLUSIONS
Pregnant women with autoimmune conditions are at a greater risk of developing adverse pregnancy outcomes. Further research is required to develop better preconception to postnatal care for women with autoimmune conditions.
Topics: Infant, Newborn; Pregnancy; Infant; Female; Humans; Diabetes Mellitus, Type 1; Celiac Disease; Premature Birth; Autoimmune Diseases; Lupus Erythematosus, Systemic; Scleroderma, Systemic; Crohn Disease; Inflammatory Bowel Diseases
PubMed: 38438886
DOI: 10.1186/s12916-024-03309-y