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ID PMID Title PublicationDate abstract
34060032 Purification of Functional Platelet Mitochondria Using a Discontinuous Percoll Gradient. 2021 The isolation of mitochondria is gaining importance in experimental and clinical laboratory settings. Of interest, mitochondria and mitochondrial components (i.e., circular mitochondrial DNA, N-formylated peptides, cardiolipin) have been involved in several human inflammatory pathologies, such as cancer, Alzheimer's disease, Parkinson's disease, and rheumatoid arthritis. While several mitochondrial isolation methods have been previously published, these techniques are aimed at yielding mitochondria from cell types other than platelets. In addition, little information is known on the number of platelet-derived microvesicles that can contaminate the mitochondrial preparation or even the overall quality as well as functional and structural integrity of mitochondria. Here we describe a purification method, using a discontinuous Percoll gradient, yielding mitochondria of high purity and integrity from human platelets.
33719967 Tocilizumab: From Rheumatic Diseases to COVID-19. 2021 Tocilizumab is a humanised interleukin-6 receptor-inhibiting monoclonal antibody that is currently approved for the treatment of rheumatoid arthritis and other immune-related conditions. Recently, tocilizumab has been investigated as a possible treatment for severe coronavirus-induced disease 2019 (COVID-19). Despite the lack of direct antiviral effects, tocilizumab could reduce the immune-induced organ damage caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) infection. Until recently, most reports on tocilizumab for COVID-19 included a limited number of patients, preventing an overall evaluation of its efficacy and safety for this specific condition. Therefore, we reviewed the literature regarding the physiopathological rationale of tocilizumab for COVID-19 and its outcomes. We searched the MEDLINE database with the string "(SARS-CoV-2 OR coronavirus OR COVID-19 OR MERS- cov OR SARS-cov) AND (IL-6 OR interleukin 6 OR tocilizumab)". While the scientific rationale supporting tocilizumab for COVID-19 is solid, the evidence regarding the outcomes remains controversial. Available data and results from ongoing trials will provide useful information in the event of new COVID-19 outbreaks or future pandemics from different coronaviruses.
34924555 Genome-wide association study of pain sensitivity assessed by questionnaire and the cold p 2021 Dec 17 We deployed an online pain sensitivity questionnaire (PSQ) and an at-home version of the cold pressor test (CPT) in a large genotyped cohort. We performed genome-wide association studies (GWAS) on the PSQ score (25,321 participants) and CPT duration (6,853). We identified one new genome-wide significant locus associated with the PSQ score, which was located in the TSSC1 (also known as EIPR1) gene (rs58194899, OR = 0.950 [0.933-0.967], P-value = 1.9*10-8). Although high pain sensitivity measured by both PSQ and CPT was associated with individual history of chronic and acute pains, genetic correlation analyses surprisingly suggested an opposite direction: PSQ score was inversely genetically correlated neck and shoulder pain (rg = -0.71), rheumatoid arthritis (-0.68), and osteoarthritis (-0.38), and with known risk factors, such as the length of working week (-0.65), smoking (-0.36), or extreme BMI (-0.23). Gene-based analysis followed by pathway analysis showed that GWAS results were enriched for genes expressed in the brain and involved in neuronal development and glutamatergic synapse signaling pathways. Finally, we confirmed that females with red hair were more sensitive to pain and found that genetic variation in the MC1R gene was associated with an increase in self-perceived pain sensitivity as assessed by the PSQ.
34745469 Patient-Related Risk Factors for the Development of Lumbar Spine Adjacent Segment Patholog 2021 OBJECTIVES: Individual risk factors for the development of adjacent segment pathology (ASP) need to be investigated and identified to address possible modifiable factors in advance and improve outcomes and reduce medical costs. This study aimed to review the literature regarding patient-related risk factors and sagittal alignment parameters associated with ASP development. METHODS: The authors performed an extensive review of the literature addressing the objectives mentioned earlier. RESULTS: Certain patient factors such as age, gender, obesity, preexisting degeneration, osteoporosis, postmenopausal state, rheumatoid arthritis, and facet tropism may contribute to adjacent segment degeneration. Genetic influences, such as polymorphisms of the vitamin D receptor and collagen IX genes, can also be a potential cause for disc degeneration with consequent deterioration of the motion segment.The influence of sagittal imbalances, particularly after lumbar fusion, is a significant parameter to be taken into account as an independent risk factor for ASP development. CONCLUSIONS: Patient-specific risk factors, such as age, gender, obesity, preexisting degeneration, and genetic features increase the likelihood of developing ASP. On the other hand, sagittal alignment plays a significant role in the development of this condition.
34618208 [Artificial intelligence-supported treatment in rheumatology : Principles, current situati 2021 Dec Computer-guided clinical decision support systems have been finding their way into practice for some time, mostly integrated into electronic medical records. The primary goals are to improve the quality of treatment, save time and avoid errors. These are mostly rule-based algorithms that recognize drug interactions or provide reminder functions. Through artificial intelligence (AI), clinical decision support systems can be disruptively further developed. New knowledge is constantly being created from data through machine learning in order to predict the individual course of a patient's disease, identify phenotypes or support treatment decisions. Such algorithms already exist for rheumatological diseases. Automated image recognition and disease prediction in rheumatoid arthritis are the most advanced; however, these have not yet been sufficiently tested or integrated into existing decision support systems. Rather than dictating the AI-assisted choice of treatment to the doctor, future clinical decision systems are seen as hybrid decision support, always involving both the expert and the patient. There is also a great need for security through comprehensible and auditable algorithms to sustainably guarantee the quality and transparency of AI-assisted treatment recommendations in the long term.
34401710 The potential role of glycosaminoglycans in serum amyloid A fibril formation by in silico 2021 Dec Serum amyloid A (SAA) is actively involved in such pathological processes as atherosclerosis, rheumatoid arthritis, cancer and Alzheimer's disease by its aggregation. One of the factors that can attenuate its aggregation and so affects its physiological role is its interactions with glycosminoglycans (GAGs), linear anionic periodic polysaccharides. These molecules located in the extracellular matrix of the cell are highly variable in their chemical composition and sulfation patterns. Despite the available experimental evidence of SAA-GAG interactions, no mechanistic details at atomic level have been reported for these systems so far. In our work we aimed to apply diverse computational tools to characterize SAA-GAG complexes formation and to answer questions about their potential specificity, energetic patterns, particular SAA residues involved in these interactions, favourable oligomeric state of the protein and the potential influence of GAGs on SAA aggregation. Molecular docking, conventional and replica exchange molecular dynamics approaches were applied to corroborate the experimental knowledge and to propose the corresponding molecular models. SAA-GAG complex formation was found to be electrostatics-driven and rather unspecific of a GAG sulfation pattern, more favorable for the dimer than for the monomer when binding to a short GAG oligosaccharide through its N-terminal helix, potentially contributing to the unfolding of this helix, which could lead to the promotion of the protein aggregation. The data obtained add to the specific knowledge on SAA-GAG systems and deepen the general understanding of protein-GAG interactions that is of a considerable value for the development of GAG-based approaches in a broad theurapeutic context.
33981931 Autoimmune regulation of chronic pain. 2021 Chronic pain is an unpleasant and debilitating condition that is often poorly managed by existing therapeutics. Reciprocal interactions between the nervous system and the immune system have been recognized as playing an essential role in the initiation and maintenance of pain. In this review, we discuss how neuroimmune signaling can contribute to peripheral and central sensitization and promote chronic pain through various autoimmune mechanisms. These pathogenic autoimmune mechanisms involve the production and release of autoreactive antibodies from B cells. Autoantibodies-ie, antibodies that recognize self-antigens-have been identified as potential molecules that can modulate the function of nociceptive neurons and thereby induce persistent pain. Autoantibodies can influence neuronal excitability by activating the complement pathway; by directly signaling at sensory neurons expressing Fc gamma receptors, the receptors for the Fc fragment of immunoglobulin G immune complexes; or by binding and disrupting ion channels expressed by nociceptors. Using examples primarily from rheumatoid arthritis, complex regional pain syndrome, and channelopathies from potassium channel complex autoimmunity, we suggest that autoantibody signaling at the central nervous system has therapeutic implications for designing novel disease-modifying treatments for chronic pain.
33968085 Partners in Leaky Gut Syndrome: Intestinal Dysbiosis and Autoimmunity. 2021 The intestinal surface is constitutively exposed to diverse antigens, such as food antigens, food-borne pathogens, and commensal microbes. Intestinal epithelial cells have developed unique barrier functions that prevent the translocation of potentially hostile antigens into the body. Disruption of the epithelial barrier increases intestinal permeability, resulting in leaky gut syndrome (LGS). Clinical reports have suggested that LGS contributes to autoimmune diseases such as type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and celiac disease. Furthermore, the gut commensal microbiota plays a critical role in regulating host immunity; abnormalities of the microbial community, known as dysbiosis, are observed in patients with autoimmune diseases. However, the pathological links among intestinal dysbiosis, LGS, and autoimmune diseases have not been fully elucidated. This review discusses the current understanding of how commensal microbiota contributes to the pathogenesis of autoimmune diseases by modifying the epithelial barrier.
33585138 Etiological Association Between Psoriasis and Thyroid Diseases. 2021 Jan 12 Psoriasis is a chronic relapsing/remitting autoimmune disease affecting skin and fingernails. It is associated with many other autoimmune diseases such as rheumatoid arthritis, celiac disease, Crohn's disease, and thyroid diseases. Two important autoimmune thyroid diseases - Hashimoto's thyroiditis (hypothyroidism) and Grave's disease (hyperthyroidism) - affect the body's significant organs such as the brain, muscles, digestive function, and the skin. Although some studies have established the connection between psoriasis and thyroid diseases with autoimmunity, our article provides an in-depth analysis of the connection between these two diseases and other common etiological factors associated with them, along with autoimmunity. We reviewed articles from PubMed using regular keywords and Medical Subject Headings (MeSH) keywords and finalized 45 articles to find an association between these two diseases. These articles showed that this association is more prevalent in obese patients and late-onset psoriasis. Most of the articles showed a positive association, but few articles showed no connection between them. However, there is no concrete explanation to prove the association due to limited research; additional studies are necessary. It requires the attention of both clinicians and researchers to develop a universal drug that will work on both diseases, and also thyroid evaluation could be included in psoriatic patient care so that there is a possibility to decrease cost and efforts while treating these diseases.
33584321 The Effect of Inflammation on Bone. 2020 Bone remodeling is the continual process to renew the adult skeleton through the sequential action of osteoblasts and osteoclasts. Nuclear factor RANK, an osteoclast receptor, and its ligand RANKL, expressed on the surface of osteoblasts, result in coordinated control of bone remodeling. Inflammation, a feature of illness and injury, plays a distinct role in skewing this process toward resorption. It does so via the interaction of inflammatory mediators and their related peptides with osteoblasts and osteoclasts, as well as other immune cells, to alter the expression of RANK and RANKL. Such chemical mediators include TNFα, glucocorticoids, histamine, bradykinin, PGE2, systemic RANKL from immune cells, and interleukins 1 and 6. Conditions, such as periodontal disease and alveolar bone erosion, aseptic prosthetic loosening, rheumatoid arthritis, and some sports related injuries are characterized by the result of this process. A thorough understanding of bone response to injury and disease, and ability to detect such biomarkers, as well as imaging to identify early structural and mechanical property changes in bone architecture, is important in improving management and outcomes of bone related pathology. While gut health and vitamin and mineral availability appear vitally important, nutraceuticals also have an impact on bone health. To date most pharmaceutical intervention targets inflammatory cytokines, although strategies to favorably alter inflammation induced bone pathology are currently limited. Further research is required in this field to advance early detection and treatments.
33461110 Modulation of inflammatory responses by gastrointestinal Prevotella spp. - From associatio 2021 Feb Numerous studies have associated alterations in the gut microbiota composition with almost every known inflammatory disease. However, proving the biological relevance of distinct microbial signatures and linking specific microorganisms to host phenotypes, remains a considerable challenge. Correspondingly, increased abundance of members of Prevotella genus within microbial communities colonizing distinct mucosal surfaces has been found in individuals diagnosed with rheumatoid arthritis, periodontitis, metabolic disorders, and intestinal and vaginal dysbiosis. Still, the role of Prevotella spp. in the incidence of these diseases continues to be debated. For many years, poor understanding of Prevotella biology could be in large part attributed to the lack of experimental tools. However, in the recent years significant advances have been made towards overcoming these limitations, including increased number of isolates and improved understanding of genetic diversity. Besides discussing the most relevant associations between Prevotella spp. and inflammatory disorders, in the present review we examine the recent efforts to expand the Prevotella experimental "toolbox" and we highlight remaining experimental challenges that should advance future research and our understanding of Prevotella-host interplay.
34273245 Using Parallel Streams of Evidence to Inform Guideline Development: The Case of the 2021 A 2021 Sep OBJECTIVE: We aim to describe an evidence synthesis approach using parallel streams of evidence that informed the development of the 2021 American College of Rheumatology (ACR) guideline for the management of rheumatoid arthritis (RA). METHODS: We developed the evidence synthesis approach using parallel streams of evidence in multiple rounds of discussion, piloting, feedback, and revisions. A number of working groups involving ACR staff, content experts, and methodologists coordinated to develop and implement the approach. RESULTS: We used a major stream of evidence that identified evidence specific to the clinical questions being addressed in the guideline (ie, we were able to match relevant articles to specific questions). We also used additional streams that identified data that applied across multiple questions. We describe in this article the different steps of the major stream, ie, screening and tagging, matching articles to question clusters, matching articles to individual questions, data abstraction and analysis, and Grading of Recommendations Assessment, Development and Evaluation (GRADEing). We then describe how we packaged the parallel streams of evidence into standardized structured tables to facilitate formulating the recommendations. These tables included information for the following factors: desirable effects, undesirable effects, certainty of evidence, valuation of outcomes, cost of interventions, and cost-effectiveness of interventions. The approach allowed us to match eligible articles for 47 of 81 clinical questions. We identified no eligible articles that addressed the remaining 34 questions. CONCLUSION: We were successful in using parallel streams of evidence to inform the development of the 2021 ACR guideline for the management of RA.
34124987 Topical Erythropoietin for Treatment of Scleral Necrosis. 2021 Jun 14 Purpose: To investigate the safety and efficacy of topical erythropoietin for the treatment of scleral necrosis.Methods: This study enrolled eight consecutive patients with scleral necrosis due to previous ocular surgery, rheumatoid arthritis-associated necrotizing anterior scleritis, and thermal and chemical burns. Conventional treatments failed to heal avascular scleral lesions in all eyes. Patients were treated with topical erythropoietin (3000 IU/mL) four times a day.Results: The mean patient age was 37.6 ± 15.5 years. The interval between the development of scleral necrosis and initiation of topical erythropoietin was 25.6 ± 12.0 days. The necrotic sclera completely healed within 31.9 ± 16.9 days in all patients. The avascular lesions did not recur, and there was no evidence of side effects during the study.Conclusion: Our results showed that topical erythropoietin could be safely used to manage scleral necrosis. Randomized clinical trials are needed to further explore the efficacy of this intervention in patients with avascular scleral lesions.
33971346 CCR6-CCL20 axis as a therapeutic target for autoimmune diseases. 2021 Jul Chemokine receptor CCR6 is expressed on various cells such as B cells, immature dendritic cells, innate lymphoid cells (ILCs), regulatory CD4 T cells, and Th17 cells. CCL20 is the only known high-affinity ligand that binds to CCR6 and drives CCR6(+) cells' migration in tissues. CCL20 is mainly produced by epithelial cells, and its expression is increased by several folds under inflammatory conditions. Genome-wide association studies (GWAS) in patients with inflammatory bowel disease (IBD), psoriasis (PS), rheumatoid arthritis (RA), and multiple sclerosis (MS) showed a very strong correlation between the expression of CCR6 and disease severity. It has been shown that disruption of CCR6-CCL20 interaction by using antibodies or antagonists prevents the migration of CCR6 expressing immune cells at the site of inflammation and reduces the severity of the disease. This review discussed the importance of the CCR6-CCL20 axis in IBD, PS, RA, and MS, and recent advances in targeting the CCR6-CCL20 in controlling these autoimmune diseases.
33208614 Not All Heart Uptakes on 99mTc-DPD Scintigraphy Are Amyloidosis: Chloroquine-Induced Cardi 2021 Apr 1 This was the case of a 61-year-old woman with a medical history significant for hypertension and rheumatoid arthritis treated with chloroquine for the last 10 years. She was admitted to our hospital for heart failure symptoms. Echocardiography revealed severe concentric left ventricular hypertrophy. Serum and urine immunofixation electrophoresis and serum light chain assay were negative. No late gadolinium enhancement was observed on cardiovascular magnetic resonance. 99mTc-99mTc-DPD (3,3-diphosphono-1,2-propanodicarboxylic acid) scintigraphy showed myocardial uptake (Perugini score 2/3). Genetic testing excluded hereditary transthyretin cardiac amyloidosis. Endomyocardial biopsy analysis did not show findings suggestive of amyloidosis but consistent with chloroquine toxicity. Chloroquine-mediated cardiotoxicity is rare, and there are very few reports about bone scintigraphy imaging features.
34840840 Management of a Complex Supracondylar Periprosthetic Femur Fracture with Intramedullary St 2021 Supracondylar periprosthetic femoral fractures occurring above total knee replacements have been considered a rare entity. However, they continue to increase in frequency with the increasing number of arthroplasties and the improvement in morbidity and mortality in the concerned patient population. The management of periprosthetic distal femoral fractures is a challenging orthopedic problem. In this brief communication, a case of 49-year-old woman with rheumatoid arthritis who sustained a low distal comminuted periprosthetic femoral fracture is presented. Her fracture was eventually managed with an intramedullary fibular strut allograft and bilateral locking plate placement reaching satisfactory healing and restoration of alignment. The primary aim of this report is to provide insight into this novel technique as a successful alternative to other standard surgical options.
34833168 A Review of the Effects of Collagen Treatment in Clinical Studies. 2021 Nov 9 Collagen, an abundant extracellular matrix protein, has been found to have a lot of pharmaceuticals, medicine, food, and cosmetics applications. Increased knowledge of collagen sources, extraction techniques, structure, and properties in the last decades has helped develop more collagen-based products and tissue engineering biomaterials. Collagen products have been playing an important role in benefiting the health of the human body, especially for aging people. In this paper, the effects of collagen treatment in different clinical studies including skin regeneration, bone defects, sarcopenia, wound healing, dental therapy, gastroesophageal reflux, osteoarthritis, and rheumatoid arthritis have been reviewed. The collagen treatments were significant in these clinical studies. In addition, the associations between these diseases were discussed. The comorbidity of these diseases might be closely related to collagen deficiency, and collagen treatment might be a good choice when a patient has more than one of these diseases, including the coronavirus disease 2019 (COVID-19). It concludes that collagen-based medication is useful in treating comorbid diseases and preventing complications.
34589505 IL-33 in Rheumatic Diseases. 2021 Interleukin-33 (IL-33) is a nuclear factor mainly expressed in barrier epithelium, endothelial cells, and fibroblast reticular cells. Some inflammatory cells also express IL-33 under certain conditions. The important role of IL-33 in allergic reactions, helminth infection, cancer, tissue fibrosis, chronic inflammation, organ transplantation, and rheumatic immune diseases has been extensively studied in recent years. IL-33 primarily activates various circulating and tissue-resident immune cells, including mast cell, group 2 innate lymphoid cell (ILC2), regulatory T cell (Treg), T helper 2 cell (Th2), natural killer cell (NK cell), and macrophage. Therefore, IL-33 plays an immunomodulatory role and shows pleiotropic activity in different immune microenvironments. The IL-33/serum stimulation-2 (ST2) axis has been shown to have a detrimental effect on rheumatoid arthritis, systemic lupus erythematosus, and other rheumatic diseases. Interestingly, IL-33 also plays a protective role in the repair of barrier epithelium and the activation of Tregs. Therefore, the role of IL-33/ST2 depends on the underlying pathological conditions in rheumatic diseases. This review focuses on the dual role of the IL-33/ST2 axis in rheumatic diseases.
34445929 Dysregulated translational factors and epigenetic regulations orchestrate in B cells contr 2021 Aug 27 B cells play a crucial role in antigen presentation, antibody production and pro-/anti-inflammatory cytokine secretion in adaptive immunity. Several translational factors including transcription factors and cytokines participate in the regulation of B cell development, with the cooperation of epigenetic regulations. Autoimmune diseases are generally characterized with autoreactive B cells and high-level pathogenic autoantibodies. The success of B cell depletion therapy in mouse model and clinical trials has proven the role of B cells in pathogenesis of autoimmune diseases. The failure of B cell tolerance in immune checkpoints results in accumulated autoreactive naïve B (B(N)) cells with aberrant B cell receptor signaling and dysregulated B cell response, contributing to self-antibody-mediated autoimmune reaction. Dysregulation of translational factors and epigenetic alterations in B cells has been demonstrated to correlate with aberrant B cell compartment in autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren's syndrome, multiple sclerosis, diabetes mellitus and pemphigus. This review is intended to summarize the interaction of translational factors and epigenetic regulations that are involved with development and differentiation of B cells, and the mechanism of dysregulation in the pathogenesis of autoimmune diseases.
34213828 Drivers of phenotypic variation in cartilage: Circadian clock genes. 2021 Aug Endogenous homeostasis and peripheral tissue metabolism are disrupted by irregular fluctuations in activation, movement, feeding and temperature, which can accelerate negative biological processes and lead to immune reactions, such as rheumatoid arthritis (RA) and osteoarthritis (OA). This review summarizes abnormal phenotypes in articular joint components such as cartilage, bone and the synovium, attributed to the deletion or overexpression of clock genes in cartilage or chondrocytes. Understanding the functional mechanisms of different genes, the differentiation of mouse phenotypes and the prevention of joint ageing and disease will facilitate future research.