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ID PMID Title PublicationDate abstract
34188295 A Comparative Study to Evaluate the Efficacy and Cost of Rituximab versus Dexamethasone Cy 2021 Mar INTRODUCTION: Rituximab is slowly getting recognized as a promising steroid-sparing agent in the treatment of moderate to severe cases of pemphigus vulgaris (PV). We evaluated and compared the effectiveness, safety, and cost of therapy of rituximab versus dexamethasone cyclophosphamide pulse (DCP) in Indian patients with PV. MATERIALS AND METHODS: It is a retrospective data analysis, from the Immunobullous disease clinic in a tertiary centre of eastern India, of management of PV. In our institute we use either rituximab or DCP for the management of moderate to severe cases of PV, depending on that we retrospectively divided the treated cases of PV in two groups. Patients who were treated with rheumatoid arthritis (RA) protocol of rituximab were considered to be group 1. Patients who were treated with DCP were included in group 2. Response was assessed by pemphigus area, and activity score (PAAS), Dermatology life quality index (DLQI); photographic documentation, and blood parameters were monitored. RESULTS: Both groups showed significant improvement in PAAS and DLQI, the improvement was faster and well sustained in the rituximab group. In terms of safety and development of new vesicles, rituximab had a better profile with only 1 patient having adverse effects and none with new vesicles as compared to DCP (3 had adverse effects and 2 developed new vesicles). CONCLUSIONS: Rituximab offers the advantage of early and prolonged remission, lesser adverse effects, better effectiveness, less risk of relapses, faster improvement of PAAS, and DLQI. Though rituximab is an expensive drug, but on evaluating the cost of whole therapy, it was seen that rituximab infusions are actually cheaper compared to DCP pulse. We suggest, rituximab can be used as the first-line of therapy for pemphigus vulgaris in the Indian context.
34112749 Acute Pancreatitis with an Ongoing Pancreatic Duct Leak Complicated by Refractory Pleural 2021 Jun 11 BACKGROUND Acute pancreatitis causes a significant systemic inflammatory response that affects multiple organs. Pulmonary complications include pleural effusions, hypoxia, atelectasis, and acute respiratory distress syndrome. Pleural effusion is an indicator of poor prognosis in pancreatitis. This case report supports the few existing reports about best practice for the diagnosis and treatment of a pancreatic duct leak causing refractory right pleural effusion. CASE REPORT In this case report, a woman with long-term rheumatoid arthritis and recent severe gallstone pancreatitis required hospital readmission for progressive shortness of breath from recurrent massive right pleural effusion from the pancreatitis with an ongoing pancreatic leak and a pseudocyst. She had diagnostic thoracentesis and magnetic resonance cholangiopancreatography (MRCP) that was followed by endoscopic retrograde cholangiopancreatography (ERCP) and stent placement as a therapeutic procedure, with complete resolution of her symptoms. CONCLUSIONS This case report demonstrates an atypical presentation of complications from severe pancreatitis. MRCP is the criterion standard and best initial test for diagnosing a fistula. When possible, ERCP is preferred for the initial evaluation and treatment of pancreatic leaks and fistulas. In the present case report, treatment with endoscopic cystogastrostomies was effective for the internal drainage of the pseudocyst, pancreatic duct leak, and eventual resolution of the pleural effusion.
34053057 Whole Exome Sequencing for the Identification of Mutations in CD8(+) T-Cells. 2021 Advances in next-generation sequencing and in particular whole exome sequencing (WES) have provided an innovative opportunity to perform a mutational screening of the entire coding region of the genome down to the single base, enhancing the discovery of causal mutations important for disease treatment and management. Recently, the accumulation of germline mutations in expanded CD8(+) T-cells has been found to have a pathogenic significance in autoimmune diseases such as rheumatoid arthritis, and, on the other hand, this type of mutations may act in combination with newly acquired somatic mutations modulating tumorigenesis, evolution, and cancer recurrence determining the clinical outcome. Therefore, we describe a protocol for identifying and characterizing germline single nucleotide variants (SNVs) and small deletions (Indels) from next-generation WES data of CD8(+) T-cells coming from patients with autoimmune diseases and comparing them to matching control samples. Conversely, the same protocol can be applied for identifying and characterizing germline SNVs from CD8(+) T-cells isolated from tumor samples with a non-favorable clinical outcome compared to those from patients with a favorable clinical outcome used as controls.
33535350 [Research progress of silica-associated autoimmune diseases]. 2021 Jan 20 Silicosis is caused by long-term exposure to dust containing crystalline silica. However, silica exposure, which may lead to autoimmune dysfunction, is associated with autoimmune diseases such as rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, idiopathic inflammatory myopathy and anti-central granulocyte cytoplasmic antibody associated vasculitis. With silica exposure autoimmune diseases may exist with or without silicosis. This article reviews recent research on silica-associated autoimmune diseases such as the concept, epidemiology, clinical characteristics and potential mechanisms to improve the understanding of the disease and promote the formulation of diagnostic criteria and treatment plans.
34858474 Calculation of Similarity Between 26 Autoimmune Diseases Based on Three Measurements Inclu 2021 Autoimmune diseases (ADs) are a broad range of diseases in which the immune response to self-antigens causes damage or disorder of tissues, and the genetic susceptibility is regarded as the key etiology of ADs. Accumulating evidence has suggested that there are certain commonalities among different ADs. However, the theoretical research about similarity between ADs is still limited. In this work, we first computed the genetic similarity between 26 ADs based on three measurements: network similarity (NetSim), functional similarity (FunSim), and semantic similarity (SemSim), and systematically identified three significant pairs of similar ADs: rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), myasthenia gravis (MG) and autoimmune thyroiditis (AIT), and autoimmune polyendocrinopathies (AP) and uveomeningoencephalitic syndrome (Vogt-Koyanagi-Harada syndrome, VKH). Then we investigated the gene ontology terms and pathways enriched by the three significant AD pairs through functional analysis. By the cluster analysis on the similarity matrix of 26 ADs, we embedded the three significant AD pairs in three different disease clusters respectively, and the ADs of each disease cluster might have high genetic similarity. We also detected the risk genes in common among the ADs which belonged to the same disease cluster. Overall, our findings will provide significant insight in the commonalities of different ADs in genetics, and contribute to the discovery of novel biomarkers and the development of new therapeutic methods for ADs.
33817310 Metabolic profiling of fatty acids in Tripterygium wilfordii multiglucoside- and triptolid 2021 Tripterygium wilfordii multiglucoside (TWM) is a fat-soluble extract from a Chinese herb T. wilfordii, that's used in treating rheumatoid arthritis, nephrotic syndrome and other skin diseases. Triptolide (TP) is a major active component in TWM. However, clinical applications of TWM are limited by its various toxicities especially hepatotoxicity. In recent studies, it has been reported that drug-induced liver injury (DILI) could induce the disorder of lipid metabolism in animals. Hence, this study focuses on the metabolic profile of fatty acids in TWM- and TP-induced liver-injured rats. In serum and liver tissue, 16 free and 16 esterified fatty acids were measured by gas chromatography coupled with mass spectrometry. Metabolic profile of serum fatty acids in rats with liver injury was identified by multivariate statistical analysis. The fatty acid levels in the serum of TWM- and TP-treated rats significantly decreased, whereas those in the liver tissue of TWM- and TP-treated rats obviously increased when compared with the vehicle-treated rats. Four free fatty acids were identified as candidate biomarkers of TWM- and TP-induced liver injury. Therefore, the targeted metabolomic method may be used as a complementary approach for DILI diagnosis in clinic.
33726947 ILC in chronic inflammation, cancer and targeting with biologicals. 2021 Aug Since their discovery, Innate Lymphoid Cells (ILC) have emerged as important effector cells, serving multiple roles in maintaining tissue homeostasis and responding to tissue insults. As such, dysregulations of their function and distribution have been observed in a variety of immune-mediated diseases, suggesting a specific role for ILC in the pathophysiology of several disorders including chronic inflammation and cancer. Here, we provide an updated view on ILC biology dissecting their pathological or protective contribution in chronic inflammatory diseases such as multiple sclerosis, inflammatory bowel diseases, psoriasis, rheumatoid arthritis, asthma and COPD, atherosclerosis, also exploring ILC role in tumor surveillance and progression. Throughout the review, we will also highlight how the potential dual role of these cells for protective or pathogenic immunity in many inflammatory diseases makes them interesting targets for the development of novel therapeutic strategies, particularly promising.
33629312 Impact of miR-155 (rs767649 A>T) and miR-146a (rs57095329 A>G) polymorphisms in System Lup 2021 Feb OBJECTIVE: Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory disease. miR-155 and miR-146a were expressed in many autoimmune diseases such as rheumatoid arthritis. The aim of this study was to examine miR-155 rs767649 and miR-146a rs57095329 polymorphisms in SLE susceptibility in an Egyptian cohort and to investigate the correlation between them and clinical data and disease activity. PATIENTS AND METHODS: The two SNPs were analyzed in 120 patients with SLE and 100 healthy controls using RT-PCR. RESULTS: The TT genotype and T allele of miR-155 rs767649 were associated with a significant increase in the risk of SLE, particularly in females. On the other hand, miR-146a (rs57095329) polymorphism was not associated with SLE risk. The AT/TT genotypes of miR-155 rs767649 showed higher distributions among patients with higher SLEDAI and nephritis. CONCLUSIONS: This study had demonstrated for the first time the association between miR-155 rs767649 and the risk of development of SLE in an Egyptian cohort, mostly in females.
33585266 The Role of Porphyromonas gingivalis Outer Membrane Vesicles in Periodontal Disease and Re 2020 Periodontal disease is a chronic infectious disease associated with a variety of bacteria, which can cause damage to the periodontal support structure and affect a variety of systemic system diseases such as cancer, cardiovascular disease, diabetes, rheumatoid arthritis, non-alcoholic fatty liver, and Alzheimer's disease. Porphyromonas gingivalis (P. gingivalis) is the most important pathogenic bacteria for periodontal disease. It can produce outer membrane vesicles (OMVs) and release them into the environment, playing an important role in its pathogenesis. This article focuses on P. gingivalis OMVs, reviews its production and regulation, virulence components, mode of action and related diseases, with a view to providing new ideas for the prevention and treatment of diseases related to P. gingivalis infections.
32896251 Up-regulation of autophagy by etanercept treatment results in TNF-induced apoptosis reduct 2021 May OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune systemic inflammatory disease associated with a high prevalence of atherosclerosis. Endothelial dysfunction has emerged as a potentially valuable prognostic tool in predicting the development of atherosclerosis. Tumour necrosis factor (TNF) is the main cytokine involved in RA pathogenesis, exerting a pro-atherogenic role. TNF-inhibitors are effective treatments in RA, also improving endothelial function. Regarding this, no experimental data are known about the involvement of etanercept. We investigated the contribution of TNF to endothelial dysfunction and the effect of in vitro treatment with etanercept, with a special focus on autophagy and apoptosis pathways. METHODS: Autophagy and apoptosis were evaluated by Western blot and flow cytometry in EA.hy926 endothelial cells treated with TNF alone or in combination with etanercept for 24h. RESULTS: Blocking autophagy, TNF was able to induce endothelial cell apoptosis. Co-treatment with etanercept reverted this effect, up-regulating the autophagy pathway. CONCLUSIONS: Our results confirm the protective role of etanercept, by restoring autophagy on TNF-induced endothelial damage.
31985437 AIEpred: An Ensemble Predictive Model of Classifier Chain to Identify Anti-Inflammatory Pe 2021 Sep Anti-inflammatory peptides (AIEs) have recently emerged as promising therapeutic agent for treatment of various inflammatory diseases, such as rheumatoid arthritis and Alzheimer's disease. Therefore, detecting the correlation between amino acid sequence and its anti-inflammatory property is of great importance for the discovery of new AIEs. To address this issue, we propose a novel prediction tool for accurate identification of peptides as anti-inflammatory epitopes or non anti-inflammatory epitopes. Most of all, we encode the original peptide sequence for better mining and exploring the information and patterns, based on the three feature representations as amino acid contact, position specific scoring matrix, physicochemical property. At the same time, we exploit several feature extraction models and utilize one feature selection model, in order to construct many base classifiers from various feature representations. More specifically, we develop an effective classification model, with which we can extract and learn a set of informative features from the ensemble classifier chain model with different group of base classifiers. Furthermore, in order to test the predictive power of our model, we conduct the comparative experiments on the leave-one-out cross-validation and the independent test. It shows that our novel predictor performs great accurate for identification of AIEs as well as existing outstanding prediction tools. Source codes are available at https://github.com/guofei-tju/Ensemble-classifier-chain-model.
35145499 "Osteomicrobiology": The Nexus Between Bone and Bugs. 2021 A growing body of scientific evidence supports the notion that gut microbiota plays a key role in the regulation of various physiological and pathological processes related to human health. Recent findings have now established that gut microbiota also contributes to the regulation of bone homeostasis. Studies on animal models have unraveled various underlying mechanisms responsible for gut microbiota-mediated bone regulation. Normal gut microbiota is thus required for the maintenance of bone homeostasis. However, dysbiosis of gut microbiota communities is reported to be associated with several bone-related ailments such as osteoporosis, rheumatoid arthritis, osteoarthritis, and periodontitis. Dietary interventions in the form of probiotics, prebiotics, synbiotics, and postbiotics have been reported in restoring the dysbiotic gut microbiota composition and thus could provide various health benefits to the host including bone health. These dietary interventions prevent bone loss through several mechanisms and thus could act as potential therapies for the treatment of bone pathologies. In the present review, we summarize the current knowledge of how gut microbiota and its derived microbial compounds are associated with bone metabolism and their roles in ameliorating bone health. In addition to this, we also highlight the role of various dietary supplements like probiotics, prebiotics, synbiotics, and postbiotics as promising microbiota targeted interventions with the clinical application for leveraging treatment modalities in various inflammatory bone pathologies.
34944704 Neutrophil Extracellular Traps in Skin Diseases. 2021 Dec 12 Neutrophils are the primary innate immune cells, and serve as sentinels for invading pathogens. To this end, neutrophils exert their effector functions via phagocytosis, degranulation, reactive oxygen species generation, and neutrophil extracellular trap (NET) release. Pathogens and pathogen-derived components trigger NET formation, leading to the clearance of pathogens. However, NET formation is also induced by non-related pathogen proteins, such as cytokines and immune complexes. In this regard, NET formation can be induced under both non-sterile and sterile conditions. NETs are enriched by components with potent cytotoxic and inflammatory properties, thereby occasionally damaging tissues and cells and dysregulating immune homeostasis. Research has uncovered the involvement of NETs in the pathogenesis of several connective tissue diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and ANCA-associated vasculitis. In dermatology, several skin diseases clinically develop local or systemic sterile pustules and abscesses. The involvement of neutrophils and subsequent NET formation has recently been elucidated in these skin diseases. Therefore, this review highlights the NETs in these neutrophil-associated diseases.
34726124 Elevated Fab glycosylation of anti-hinge antibodies. 2021 Nov 2 OBJECTIVE: Rheumatoid arthritis (RA) is characterized by systemic inflammation and the presence of anti-citrullinated protein antibodies (ACPAs), which contain remarkably high levels of Fab glycosylation. Anti-hinge antibodies (AHAs) recognize immunoglobulin G (IgG) hinge neoepitopes exposed following cleavage by inflammation-associated proteases, and are also frequently observed in RA, and at higher levels compared to healthy controls (HCs). Here, we investigated AHA specificity and levels of Fab glycosylation as potential immunological markers for RA. METHOD: AHA serum levels, specificity, and Fab glycosylation were determined for the IgG(1/4)-hinge cleaved by matrix metalloproteinase-3, cathepsin G, pepsin, or IdeS, using enzyme-linked immunosorbent assay and lectin affinity chromatography, in patients with early active RA (n = 69) and HCs (n = 97). RESULTS: AHA reactivity was detected for all hinge neoepitopes in both RA patients and HCs. Reactivity against CatG-IgG(1)-F(ab´)(2)s and pepsin-IgG(4)-F(ab´)(2)s was more prevalent in RA. Moreover, all AHA responses showed increased Fab glycosylation levels in both RA patients and HCs. CONCLUSIONS: AHA responses are characterized by elevated levels of Fab glycosylation and highly specific neoepitope recognition, not just in RA patients but also in HCs. These results suggest that extensive Fab glycosylation may develop in response to an inflammatory proteolytic microenvironment, but is not restricted to RA.
34720604 A Case of New-Onset Systemic Lupus Erythematosus With Serositis in a Maintenance Hemodialy 2021 A 61-year-old woman with a 4-year history of maintenance hemodialysis due to end-stage renal disease of unknown cause was admitted because of a recurrent fever and abdominal pain lasting for 3 months. She had rheumatoid arthritis as a complication and had taken sulfasalazine for over 4 years. Laboratory data revealed thrombocytopenia, hypocomplementemia, a high C-reactive protein level, and positivity for antinuclear antibody and anti-double strand DNA antibody. Gallium scintigraphy showed pericarditis, pleuritis, and peritonitis. Nonscarring alopecia was also noted. She was diagnosed as having systemic lupus erythematosus (SLE). Drug-induced lupus elicited by sulfasalazine was ruled out because the symptoms did not improve even after the discontinuation of the drug upon admission. Oral prednisolone treatment markedly improved her symptoms and laboratory data. However, she later died of sepsis arising from proctitis on day 71 of admission. This report underscores the necessity of considering new-onset SLE in patients with unexplained fever and serositis, including pleuritis, peritonitis, or pericarditis, even if they are receiving maintenance dialysis.
34717068 Sex Difference in Plasma Deoxyribonuclease Activity in Rats. 2021 Dec 30 Extracellular DNA (ecDNA) activates immune cells and is involved in the pathogenesis of diseases associated with inflammation such as sepsis, rheumatoid arthritis or metabolic syndrome. DNA can be cleaved by deoxyribonucleases (DNases), some of which are secreted out of cells. The aim of this experiment was to describe plasma DNase activity in relation to extracellular DNA in adult rats, to analyse potential sex differences and to prove whether they are related to endogenous testosterone. Adult Lewis rats (n=28) of both sexes were included in the experiment. Male rats were gonadectomized or sham-operated and compared to intact female rats. Plasma ecDNA and DNase activity were measured using fluorometry and single radial enzyme diffusion assay, respectively. Concentrations of nuclear ecDNA and mitochondrial ecDNA were determined using real-time PCR. Females had 60% higher plasma DNase activity than males ( p=0.03). Gonadectomy did not affect plasma DNase in males. Neither the concentration of total ecDNA, nor nuclear or mitochondrial DNA in plasma differed between the groups. No significant correlations between DNase and ecDNA were found. From previous studies on mice, it was expected, that male rats will have higher DNase activity. In contrast, our study in rats showed the opposite sex difference. This sex difference seems not to be caused by endogenous testosterone. Interestingly, no sex differences were observed in plasma ecDNA suggesting a complex or missing association between plasma ecDNA and DNase. The observed sex difference in plasma DNase should be taken into account in animal models of ecDNA-associated diseases.
34713060 OrthoRehab: Development of a New Methodology for the Comparison Study Between Different Ty 2020 Foot dysfunction is one of the most likely consequences of rheumatoid arthritis and stroke. It is characterized by severe changes in the gait pattern due to a significant increase in the plantar flexion. Some of these dysfunctions can be compensated by using an ankle-foot orthosis. However, the clinical decision about which orthosis best suits the patient creates a real problem for physicians/therapists. Purpose: The main goal of this paper is to present a quantitative support tool that can assist the physicians/therapists in deciding which orthosis is most suitable for each subject. Methodology: In order to achieve such goal, a platform named OrthoRehab was developed, and it was tested in three conditions: without any orthosis and with two different ankle-foot orthoses. The data were acquired in the Gait Laboratory of Rehabilitation Medicine Center of Alcoitão using a VICON NEXUS 1.8.5(®) motion capture system that allows the capturing of kinematic and kinetic data. Results: The results reveal that OrthoRehab is a user-friendly, easy to apply tool that analyzes very relevant data for the clinical staff. Conclusion: The developed decision support tool, OrthoRehab, offers a quantitative analysis and provides insight to which orthosis achieves the best performance in comparison with the patient's gait pattern with no orthosis.
34514900 Nodular Regenerative Hyperplasia of the Liver in Rheumatic Disease: Cases and Review of th 2021 Jan Nodular regenerative hyperplasia (NRH) is a rare disease that is characterized by benign transformation of the hepatic parenchyma into small nodules with little to no fibrosis. Nodular regenerative hyperplasia is a cause of noncirrhotic portal hypertension. Symptoms can range from asymptomatic disease to more serious complications of portal hypertension such as esophageal varices and ascites. Nodular regenerative hyperplasia has been described in association with a variety of different rheumatologic, hematologic, and oncologic diseases, as well as in immune deficiency states and with exposures to certain toxins. Diagnosis is made by histology, and the treatment involves addressing the underlying disease. The first description of this rare disease was actually described in a patient with rheumatoid arthritis, neutropenia, and splenomegaly (Felty's Syndrome). We describe 2 cases of NRH associated with underlying rheumatic disorders, in one of which NRH was actually the presenting feature of the patient's underlying autoimmune condition. Subsequently, we provide a brief review of the literature of NRH in autoimmune disease with respect to epidemiology, cause, clinical manifestations, diagnosis, and treatment.
34430442 Progressive pseudorheumatoid dysplasia: a case series report. 2021 Jul rogressive pseudorheumatoid dysplasia (PPRD) is a rare autosomal-recessive, noninflammatory arthropathy. Several cases have been reported worldwide; however, diagnosis remains challenging. Three unrelated children with PPRD were retrospectively studied. All three patients in this study were initially misdiagnosed. The misdiagnoses included juvenile rheumatoid arthritis, myodystrophy and idiopathic short stature. The time from the onset of symptoms to a definitive diagnosis was 3 to 8 years. Clinical signs and radiological phenotypes were analyzed carefully, and they were all consistent with the characteristics of PPRD and noninflammatory polyarticular enlargement. The small joints of both the hands and lower limbs are the most affected. The imaging findings of the patients were flat vertebrae with beak- or bullet-like changes in front of the cone and peripheral metaphysis widening. DNA samples obtained from the family were sequenced to identify the causal gene using whole-exome sequencing (WES). Four Wnt1-inducible signaling pathway protein 3 (WISP3) mutations were verified. c.271delC was not reported previously. The other three mutations, namely, c.136C>T (p. Gln46*), c.667T>G (p. Cys223Gly) and c.589+2T>C, were previously identified. All three patients had a long journey to diagnosis. Early genetic diagnosis can help prevent unnecessary treatments and procedures in patients. Growth hormone is not a good choice for treatment.
33569512 Therapeutic potential of TNFα inhibitors in chronic inflammatory disorders: Past and futu 2021 Jan In the past 20 years, patients with rheumatoid arthritis (RA), Crohn's disease (CD), and other immune diseases have witnessed the impact of a great treatment advance with the availability of biological TNFα inhibitors. With 5 approved anti-TNFα biologics on the market and soon available biosimilars, patients have more treatment options and have benefited from understanding the biology of TNFα. Nevertheless, many unmet needs remain for people living with TNFα-related diseases, namely some side effects and tolerance of current anti-TNFα biologics and resistance to therapies. Furthermore, common diseases such as osteoarthritis and back/neck pain may respond to anti-TNFα therapies at early onset of symptoms. Development of new TNFα inhibitors focusing on TNFR1 specific inhibitors, preferably small molecules that can be delivered orally, is much needed.