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ID PMID Title PublicationDate abstract
30007097 Relationship of MR imaging of submandibular glands to hyposalivation in Sjögren's syndrom 2019 Jan OBJECTIVE: We analysed the correlation between magnetic resonance images of the parotid and submandibular glands and the salivary flow rate in patients with Sjögren's syndrome. METHODS: We retrospectively reviewed magnetic resonance images (heterogeneous signal-intensity distribution and gland volume on T1- and fat-suppressed T2-weighted images, and multiple high-signal-intensity spots on magnetic resonance sialograms in the parotid and submandibular glands) obtained from 66 patients who were diagnosed with Sjögren's syndrome. We evaluated the relationship between these imaging features and their salivary flow rates in stimulated and unstimulated conditions. RESULTS: We found that as the disease progressed, both the heterogeneous signal-intensity distribution and the volumes of the parotid and the submandibular glands were significantly related to the stimulated and the unstimulated salivary flow rate. These imaging features were more highly correlated in assessments of the submandibular gland than in those of the parotid gland for both stimulated and unstimulated salivary flow rates. CONCLUSIONS: Magnetic resonance image features of heterogeneity and smaller volume in the submandibular gland are reliable for predicting hyposalivation related to the progression of Sjögren's syndrome.
30189853 Rheumatoid meningitis presenting with a stroke-like attack treated with recombinant tissue 2018 Sep 6 BACKGROUND: Rheumatoid meningitis presenting with a stroke-like attack (RMSA) is a rare manifestation of rheumatoid arthritis (RA). When the patients arrive within the time-window for recombinant tissue plasminogen activator (rt-PA) infusion therapy, no diagnostic protocol has been established. CASE PRESENTATION: A 55-year-old woman was brought by ambulance to our hospital with complaints of sudden-onset dysarthria and left arm numbness. The National Institutes of Health Stroke Scale (NIHSS) score was 5, and the Alberta Stroke Program Early CT Score was 8. She was diagnosed with acute embolic stroke. At 4 h, 6 min after onset, intravenous administration of rt-PA (alteplase, 0.6 mg/kg) was started. Her neurological deficits improved rapidly, and her NIHSS score was 1. Brain MRI was then performed. There was no hemorrhagic transformation, but the MRI findings were not compatible with ischemic stroke. She had a past history of RA diagnosed 6 months earlier, and she had been treated with methotrexate (10 mg daily). She was diagnosed with RMSA, and continuous infusion of methylprednisolone 1000 mg daily was started for 3 days. The high signal intensity on the FLAIR image disappeared. CONCLUSION: CT-based decision-making for rt-PA injection is reasonable, but MRI is needed for the early diagnosis of RMSA. In this case, it is particularly important that neither adverse events nor bleeding complications were observed, suggesting the safety of CT-based thrombolytic therapy in RMSA.
29302763 Reduced myofilament component in primary Sjögren's syndrome salivary gland myoepithelial 2018 Apr Primary Sjögren's syndrome (pSS) is a solitary poorly understood autoimmune inflammatory disease by involvement of the salivary and lacrimal glands resulting in dry mouth and dry eyes. Myoepithelial cells (MECs) are cells knowing for its hybrid epithelial and mesenchymal phenotype that are important components of the salivary gland (SGs) structure aiding the expulsion of saliva from acinar lobules. In this study we investigate possible alteration in the myofilament component of MECs in SGs specimens obtained from pSS patients in comparison with healthy subjects, to evaluate MECs hypothetical involvement in the pathogenesis of pSS. The expression of alpha-smooth muscle actin (α-SMA) and p63, as MECs markers, was evaluated in bioptic specimens from pSS and healthy labial SGs through immunohistochemistry and immunofluorescence analyses; the distribution of MECs markers was quantified using Aperio ScanScope and ImageScope software to provide quantitative assessments of staining levels. Our observations demonstrated that p63 nuclear labeling in pSS MECs is preserved whereas α-SMA cytoplasmic staining is strongly and significantly reduced when compared with healthy SGs; the digital images analysis quantification of the expression of labeled α-SMA and p63 protein in the healthy and pSS MECs salivary tissues, led to results suggesting a loss of mechanical support for acini and ducts in pSS, correlated, probably, with the reduction of salivary flow that features one important aspect of pSS disease.
29517701 Evaluation of a new matrix regenerating agent in patients with Sjögren syndrome and super 2018 Mar RATIONALE: Sjögren syndrome (SS) is frequently associated with ulcerative keratitis, which is difficult to treat due to lacrimal tear deficiency and inflammation of the ocular surface. PATIENT CONCERNS: We report the successful additive effect of a matrix regenerating agent (RGTA, Cacicol) in SS patients with severe superficial ulcerative keratitis resistant to conventional therapy. DIAGNOSES: Retrospective, noncomparative case series of patients with primary or secondary SS associated with chronic diffuse keratitis. INTERVENTIONS: All patients (3 women, aged 46, 59, and 84 years) had several years of dry-eye disease history and recurrent keratitis despite having used maximal dose topical therapies including artificial tear substitutes, topical vitamin A, and cyclosporine 0.05% emulsion. All patients suffered from dry, diffuse, and chronic superficial keratitis of at least 75% of the corneal surface, with no sign of corneal neovascularization or opacity. OUTCOMES: RGTA treatment led to a rapid and marked decrease of ocular pain, burning, irritation, foreign body sensation, and improvement of visual acuity. Total diffuse keratitis healing occurred after several months of treatment. Discontinuation of RGTA administration led to the recurrence of severe keratitis; re-introduction of RGTA was successful. No local or systemic adverse effects related to treatment were reported. LESSONS: RGTA treatment was effective and safe in this small series of 3 patients suffering from SS associated with recurrent or chronic superficial ulcerative keratitis resistant to conventional therapy.
30522943 Prevalence and Demographic Characteristics of Sjögren's Syndrome in Colombia, Based on In 2020 Jul OBJECTIVE: To calculate the prevalence and describe the main demographic characteristics of Sjögren's syndrome in adults in Colombia. MATERIAL AND METHODS: Descriptive cross-sectional study which utilized data from the Integral Information System of Social Protection of the Ministry of Health of the Republic of Colombia during the years 2012 to 2016. RESULTS: 58,680 cases of Sjögren's syndrome were identified, with a prevalence in those over 18 years of age of 0.12%; 82% were women, with a female:male ratio of 4.6:1, with a higher prevalence in the age group of 65 to 69 years. The departments with the highest numbers of cases were Bogotá DC (24,885), Antioquia (9,040) and Valle del Cauca (5,277); however, the departments with the highest prevalences were Caldas (0.42%), Bogotá DC (0.32%) and Antioquia (0.14%). CONCLUSIONS: We present demographic and epidemiological information on Sjögren's syndrome in Colombia. There are very few epidemiological studies of this disorder. However, a prevalence similar to that reported in countries of the region such as Brazil (0.17%) and Argentina (0.17%) was documented.
30148469 Tooth loss in Sjögren's syndrome patients compared to age and gender matched controls. 2018 Sep 1 BACKGROUND: To analyze the prevalence and location of tooth loss in Sjögren's syndrome (SS) patients and compare them with an age- and gender-matched control group. MATERIAL AND METHODS: Dental charts and x-rays of 108 (SS) patients were retrieved from an academic dental center and special care dentistry department. For each SS patient, an age- and gender-matched non-SS patient was randomly selected. Medication, number of extractions and date and location of extractions were assessed. Differences between SS and non-SS patients were analyzed using Mann-Whitney U tests, Chi-square tests and Fisher's exact tests. RESULTS: Significantly more SS patients were edentulous compared to the non-SS group (14.8% versus 1.9%, p = 0.001). SS patients had a 61% higher risk to have experienced one or more extractions than control patients. In the SS group, there was a non-significant tendency for more maxillary teeth to have been extracted than mandibular teeth (42:34). In the control group, the number of extractions in the maxilla and mandible were comparable (21:20). When divided into sextants, the number of SS patients with one or more extractions was significantly higher than for non-SS patients for each sextant (p = 0.001 to p = 0.032). The largest difference in the proportion of patients with one or more extractions between the SS and non-SS patients occurred in the upper anterior sextant (3.4 times more frequent). CONCLUSIONS: SS patients are more prone to experience dental extractions compared to patients without SS. It could be speculated that this is related to a decreased salivary secretion.
29735923 The Spleen as an Optimal Site for Islet Transplantation and a Source of Mesenchymal Stem C 2018 May 7 This review demonstrates the unique potential of the spleen as an optimal site for islet transplantation and as a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy used to treat severe diabetes mellitus; however, its clinical outcome is currently unsatisfactory. Selection of the most appropriate transplantation site is a major factor affecting the clinical success of this therapy. The spleen has long been studied as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity, and it has recently also been shown to contribute to the regeneration of transplanted islets. However, the efficacy of transplantation in the spleen is lower than that of intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established to allow the spleen to be used for clinical transplantation. The spleen is also of interest as a mesenchymal stem cell reservoir. Splenic mesenchymal stem cells contribute to the repair of damaged tissue, and their infusion may thus be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.
29507913 Magnetic Resonance Sialography and Salivary Gland Scintigraphy of Parotid Glands in Sjögr 2018 OBJECTIVE: To assess the correlation between conventional magnetic resonance (MR) imaging and MR sialography of parotid glands with salivary gland scintigraphy in patients with Sjögren's syndrome. METHODS: A retrospective study was conducted on eight patients with Sjögren's syndrome who underwent MR imaging and salivary gland scintigraphy. Conventional MR imaging techniques, such as T1-weighted images (T1WI), T2-weighted images (T2WI), and short TI inversion recovery images (STIR) were used for changes of fat signal in the parotid gland, while the MR sialography were used for ducts dilation of the parotid gland. Regarding scintigraphy, time-activity curves of each parotid gland were analysed. The salivary gland excretion fraction was defined as A (before stimulation test (counts/20 s)) and B (after stimulation test (counts/20 s)). RESULTS: Regarding characteristic appearances of fat signal, the A/B of parotid gland with homogeneous intensity distribution (3.51 ± 0.75) was higher than that with heterogeneous intensity distribution (1.56 ± 0.66, P = 0.001). Regarding MR sialographic stages, the A/B of parotid gland with stage 0 (3.51 ± 0.75) was higher than that with stage 1 (2.03 ± 0.86, P = 0.009) and with stage 2 (1.26 ± 0.25, P = 0.000). CONCLUSION: The results suggest that MR sialography of the parotid glands is a useful noninvasive tool for evaluating the decrease of salivary gland excretion in patients with Sjögren's syndrome.
29278009 Beneficial use of serum ferritin and heme oxygenase-1 as biomarkers in adult-onset Still's 2018 Sep BACKGROUND: Heme oxygenase (HO)-1 is a heme-degrading enzyme highly expressed in monocyte/macrophage, serum levels of which may be promising biomarker for adult-onset Still's disease (AOSD). We here report data on the use of serum ferritin and HO-1 levels in AOSD. METHODS: Under the Hypercytokinemia Study Group collaboration, we collected sera from a total of 145 AOSD patients. Three independent experts judged whether the patients were definite AOSD depending on the clinical information. These 91 'definite AOSD' patients were further divided into active, remission, and relapse groups. Forty-six cases of systemic vasculitis, sepsis, etc. were included as disease controls. Serum ferritin and HO-1 levels were measured using ELISA. Associations between clinical symptoms, serum ferritin, and HO-1 were explored. Multivariate regression analysis was performed to identify independent variables associated with definite AOSD diagnosis. RESULTS: Serum ferritin and HO-1 levels were significantly higher in active and relapsed AOSD cases compared to disease controls, and were reduced by the treatment. Although a significant correlation was found between serum ferritin and HO-1 levels, a discrepancy was found in some cases such as iron-deficiency anemia. Receiver operating characteristic analysis identified optimal levels of serum ferritin (>819 ng/ml; sensitivity 76.1% and specificity 73.8%), and serum HO-1 (>30.2 ng/ml; sensitivity 84.8% and specificity 83.3%) that differentiated AOSD from controls. Interestingly, 88.9% of patients with AOSD who relapsed exceeded the cut-off value of serum HO-1 > 30.2 ng/ml, but only 50.0% exceeded serum ferritin >819 ng/ml (p = .013), suggesting that serum HO-1 levels may be a convenient indicator of AOSD disease status. Multivariate analysis identified neutrophilia, RF/ANA negativity, sore throat, and elevated serum HO-1 as independent variables associated with AOSD diagnosis. CONCLUSION: We confirmed that serum ferritin and HO-1 serve as highly specific and sensitive biomarkers for AOSD. A future prospective study with large sample size is necessary to determine whether these biomarkers could be included in Yamaguchi's Criteria.
30701893 The efficacy of rituximab in the therapy of neuromyelitis optica in a patient with Sjogren 2018 May 11 This case is the first description of the successful anti-B-cell therapy with rituximab in a patient with Sjogren's syndrome and neuromyelitis optica spectrum disorder in Russia. This article contains the literature data on clinical manifestations and methods of the diagnosis of neuromyelitis optica spectrum disorder. Furthermore, contemporary view on the pathogenesis of the combination of this disease with Sjogren's syndrome are presented here.
30312344 Severity of clinical dry eye manifestations influences protein expression in tear fluid of 2018 Ocular dryness is a characteristic feature of primary Sjögren's syndrome (pSS). This may result in dry eye disease (DED), leading to damage of the ocular surface. Additional, non-invasive diagnostic techniques are needed when evaluating pSS patients. Hence, screening for disease-specific biomarkers in biological fluid could be promising. We have previously examined the proteome of tear fluid from pSS patients through Liquid chromatography-mass spectrometry (LC-MS), and conducted a thorough ocular evaluation of patients with pSS. In this study we further explored the association between dry eye manifestations and protein expression in tear fluid of pSS patients. Medical history of 27 patients and 32 healthy controls was gathered. Subjective complaints were registered through questionnaires. Objective findings including tear osmolarity, tear film break up time (TFBUT), Schirmer's test, and ocular and corneal surface staining were also recorded. LC-MS was conducted formerly on tear fluid from all subjects in order to generate proteomic biomarker profiles. Scaffold was employed to analyse the LC-MS data for quantitative differences between patient and control groups, and the mean spectral counts were calculated for the five most upregulated proteins in relation to DED manifestations. Dysregulated cellular processes were identified in pSS patients using FunRichv3 enrichment analysis. The five most upregulated proteins previously identified in pSS patients were DNA (apurinic or apyrimidinic site) lyase (APEX1), thioredoxin-dependent peroxidase reductase (PRDX3), copine (CPNE1), aconitate hydratase (ACO2), and LIM domain only protein 7 (LMO7), in descending order. A significant increase in mean spectral counts for these proteins were observed in pSS patients with pathological DED manifestations compared to healthy controls (p<0.0001). Consequently, dysregulated cellular pathways involving innate and adaptive immunity were also detected. In conclusion, our observations suggest a relationship between presence of dry eye signs and upregulated proteins in tear fluid from patients with pSS. Further studies are needed in order to replicate the concepts explored and analyses performed in a greater cohort of pSS patients, where sensitivity and specificity of the methods conducted can also be verified further.
30284704 PF-06438179/GP1111: An Infliximab Biosimilar. 2018 Dec PF-06438179/GP1111 (Zessly(®); Ixifi(®)) [hereafter referred to as GP1111] is a biosimilar of the reference monoclonal anti-TNF-α antibody infliximab, and is approved in the EU and USA for the same indications as the reference drug, including rheumatoid arthritis (RA), Crohn's disease, ulcerative colitis (including paediatric ulcerative colitis in the EU), ankylosing spondylitis, psoriatic arthritis and plaque psoriasis; GP1111 is also approved in Japan. GP1111 has similar physicochemical characteristics and pharmacodynamic properties to those of reference infliximab, and the pharmacokinetic similarity of the agents has been shown in healthy volunteers and patients with moderate-to-severe RA despite methotrexate therapy. GP1111 demonstrated clinical efficacy equivalent to that of reference infliximab in patients with moderate-to-severe RA, despite methotrexate therapy, and was generally well tolerated in this population. The tolerability, immunogenicity and safety profiles of GP1111 were similar to those of reference infliximab, and switching from reference infliximab to GP1111 had no impact on safety, efficacy or immunogenicity. The role of reference infliximab in the management of autoimmune inflammatory conditions is well established and GP1111 provides an effective biosimilar alternative for patients requiring infliximab therapy.
29788127 Herpes Zoster in Patients Receiving JAK Inhibitors For Ulcerative Colitis: Mechanism, Epid 2018 Sep 15 Increased risk of herpes zoster (HZ) has been observed in patients with immune-mediated diseases, including rheumatoid arthritis (RA), psoriasis (PsO), and inflammatory bowel disease; this risk can be further increased by the use of immunosuppressive therapy. One advancing modality of therapy for these diseases is Janus kinase (JAK) inhibition. Tofacitinib is an oral JAK inhibitor for the treatment of RA and psoriatic arthritis, which is currently under investigation for the treatment of ulcerative colitis (UC) and was previously investigated for psoriasis. JAK inhibitors have been associated with HZ events in patients across a number of indications. The pathogenesis underlying this risk of HZ is currently unknown. An increased risk of HZ has been noted in patients receiving immunosuppressive therapies for UC, including tofacitinib. In clinical trials, there was a dose-dependent risk of HZ (higher dose linked with increased risk). However, the majority of HZ cases are nonserious and noncomplicated, mild to moderate in severity, and manageable without permanent discontinuation of treatment. This review will discuss HZ risk in patients receiving JAK inhibitors, focusing on tofacitinib with respect to the potential mechanisms and epidemiology of HZ. Current guidelines for the prevention of HZ will be highlighted, and proposed management reviewed.
29749497 miR‑486‑5p is upregulated in osteoarthritis and inhibits chondrocyte proliferation and 2018 Jul Osteoarthritis (OA) is the most common form of arthritis and is caused by the breakdown of joint cartilage. The present study aimed to investigate an effective method for the treatment of OA. It was demonstrated that, compared with other patients, patients with OA exhibited lower mRNA expression levels of SMAD family member 2 (SMAD2). MicroRNA (miR)‑486‑5p was predicted to bind with SMAD2, which was verified by dual‑luciferase reporter assay. Compared withcontrol patients who had no known history of OA or rheumatoid arthritis, patients with OA exhibited higher miR‑486‑5p expression level. Treatment with miR‑486‑5p mimics inhibited proliferation and migration of CHON‑001 human chondrocytes, and also inhibited the expression levels of type II collagen and aggrecan. However, treatment with a miR‑486‑5p inhibitor promoted proliferation and migration, and the expression of type II collagen and aggrecan. Short interfering RNA‑directed silencing of SMAD2 reversed the upregulated proliferation and migration and the expression level of type II collagen and aggrecan induced by the miR‑486‑5p inhibitor. In conclusion, the results of the present study indicated that miR‑486‑5p was upregulated in OA and may inhibit chondrocyte proliferation and migration by suppressing SMAD2.
30217258 Vitis amurensis Rupr: A review of chemistry and pharmacology. 2018 Oct 1 PURPOSE: Vitis amurensis Rupr. from the family Vitaceae, is a grape species native to the Asian continent. It is a highly attractive plant, used widely worldwide. It has been used for several hundred years as a traditional Chinese herb. The review focuses on the botanical description, traditional uses, phytochemistry, and the biological activities of Vitis amurensis Rupr. to evaluate its therapeutic potential uses. METHODS: This review summarizes the published data concerning the botanical aspects, traditional usage, phytochemistry, and pharmacology of Vitis amurensis Rupr., to evaluate its therapeutic potential as an important source of natural compounds with effect activities that benefit human health. RESULTS: Vitis amurensis Rupr. has been used for several hundred years as a traditional Chinese herb to treat stranguria, rheumatoid arthritis-associated edema, chronic hepatitis, nephritis, chronic arthritis and traumatic hemorrhage. It is a particularly rich source of the oligostilbenes, flavonoids, and anthocyanins, phytochemicals that are associated with antioxidant, anti-inflammatory, antibacterial and cardioprotective activities. Due to the presence of a multitude of bioactives, a wide array of pharmacological activities have been ascribed to different parts of this herb and individual compounds, which include antioxidant, antimicrobial, anti-inflammatory, anticancer, anti-aging, anti-melanogenic, anti-allergic and anti-viral. CONCLUSION: From a health perspective, Vitis amurensis Rupr. presents excellent options for treating various diseases due to its bioactive compounds (drug candidates) that exhibit important activities or for developing new products.
29872954 Altered microRNA expression signature in Chikungunya-infected mammalian fibroblast cells. 2018 Aug Chikungunya virus (CHIKV) infection can cause severe arthralgia and chronic arthritis in humans. MicroRNAs (miRNA) have demonstrated their potential use as biomarker in variety of human pathologies and infections. This study was conducted to understand the miRNA signature in early CHIKV infection stages. In the current study, we used TaqMan-based quantitative PCR method to identify the miRNA signature of host response upon CHIKV infection in human and mouse fibroblast cells. The GO enrichment analysis suggests that the putative target genes of these differentially expressed miRNAs are to be involved in RIG-I pathway, TGF-beta-signaling pathway, JAK-STAT-signaling pathway, MAPK-signaling pathway, cytokine-cytokine receptor interactions, and Fc gamma R-mediated phagocytosis. The results obtained in the current study and earlier studies indicate the potential use of miR15, miR-16, miR-17, let-7e, miR-125, miR-99, and miR-23a as a biomarker in CHIKV infection. miRNAs such as miR-15a, miR-16, miR-140, miR-146a, miR-155, miR203, miR223, miR-499, and miR-363 which are implicated in rheumatoid arthritis showed differential regulation in CHIKV infection. The data obtained in this study provide valuable information on CHIKV-induced miRNA expression in mammalian fibroblast cells, and suggest that CHIKV may establish infection by regulating miRNA expression profile.
29687787 Drug Induced Thrombotic Microangiopathy with Certolizumab Pegol. 2018 Sep 21 BACKGROUND: Certolizumab pegol is used to treat ankylosing spondylitis, Crohn’s disease, psoriatic arthritis, and rheumatoid arthritis. Unlike other monoclonal antibodies such as infliximab and adalimumab, certolizumab does not contain an Fc fraction and hence does not induce complement activation. In this report, we describe the case of a patient with thrombotic microangiopathy caused due to certolizumab pegol, with a brief description about the pathophysiological approach to thrombotic microangiopathy. CASE REPORT: A-39-year-old man suffering from ankylosing spondylitis for the past 10 years presented with fatigue. He had been on certolizumab pegol treatment for 6 months, starting with 400 and 200 mg every 2 weeks. He had significant nonimmune hemolytic anemia and thrombocytopenia without a disseminated intravascular coagulopathy. Schistocytes were observed in more than 10% of the erythrocytes per field. Plasma exchange along with corticosteroid treatment was started. There was a dramatic improvement within a week, and after 10 sessions of plasma exchange, the patient was discharged on corticosteroids with a tapering plan. ADAMTS13 enzyme activity was determined to be normal. CONCLUSION: The development of drug-induced thrombotic microangiopathy may be either immune-mediated or dose-dependent toxicity-mediated Anti-drug antibodies and their immunological aspects are still unclear and yet to be elucidated.
29782055 Clinical and immunological effects of adsorptive myeloid lineage leukocyte apheresis in pa 2018 Aug Adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn(®) is an extracorporeal treatment, which uses cellulose acetate (CA) beads as adsorptive leukocytapheresis carriers designed to remove elevated and potentially activated myeloid lineage leukocytes. Reports on the clinical efficacy of GMA in patients with skin lesions have appeared in the published work. Dermatological diseases, which are known to respond to GMA, include pyoderma gangrenosum, skin lesions of Behçet's disease, rheumatoid arthritis, pustular psoriasis, psoriatic arthritis, adult-onset Still's disease, Sweet's syndrome, cutaneous allergic vasculitis and systemic lupus erythematosus rashes. In association with clinical studies, efforts to understand the mechanisms of GMA have made significant progress. GMA selectively depletes elevated myeloid lineage leukocytes through binding between blood immunoglobulin G or complement iC3b, which form on the surface of CA beads and the Fcγ receptors or complement receptors expressed on the myeloid lineage cells. However, GMA has immunomodulatory effects including down-modulation of inflammatory cytokine profile, changes in leukocyte surface receptors and induction of regulatory T cells. These actions render GMA a unique non-pharmacological treatment option for patients with chronic dermatoid conditions, which are difficult to treat with pharmacological preparations.
29670999 Mechanisms involved in normal and pathological osteoclastogenesis. 2018 Jul Osteoclasts are bone-resorbing cells that play an essential role in bone remodeling. Defects in osteoclasts result in unbalanced bone remodeling and are linked to many bone diseases including osteoporosis, rheumatoid arthritis, primary bone cancer, and skeletal metastases. Receptor activator of NF-kappaB ligand (RANKL) is a classical inducer of osteoclast formation. In the presence of macrophage-colony-stimulating factor, RANKL and co-stimulatory signals synergistically regulate osteoclastogenesis. However, recent discoveries of alternative pathways for RANKL-independent osteoclastogenesis have led to a reassessment of the traditional mechanisms that regulate osteoclast formation. In this review, we provide an overview of signaling pathways and other regulatory elements governing osteoclastogenesis. We also identify how osteoclastogenesis is altered in pathological conditions and discuss therapeutic targets in osteoclasts for the treatment of skeletal diseases.
29526808 Association of NOX2 subunits genetic variants with autoimmune diseases. 2018 Sep A single nucleotide polymorphism in Ncf1 has been found with a major effect on chronic inflammatory autoimmune diseases in the rat with the surprising observation that a lower reactive oxygen response led to more severe diseases. This finding was subsequently reproduced in the mouse and the effect operates in many different murine diseases through different pathogenic pathways; like models for rheumatoid arthritis, encephalomyelitis, lupus, gout, psoriasis and psoriatic arthritis. The human gene is located in an unstable region with many variable sequence repetitions, which means it has not been included in any genome wide associated screens so far. However, identification of copy number variations and single nucleotide polymorphisms has now clearly shown that major autoimmune diseases are strongly associated with the Ncf1 locus. In systemic lupus erythematosus the associated Ncf1 polymorphism (leading to an amino acid substitution at position 90) is the strongest locus and is associated with a lower reactive oxidative burst response. In addition, more precise mapping analysis of polymorphism of other NOX2 genes reveals that these are also associated with autoimmunity. The identified genetic association shows the importance of redox control and that ROS regulate chronic inflammation instead of promoting it. The genetic identification of Ncf1 polymorphisms now opens for relevant studies of the regulatory mechanisms involved, effects that will have severe consequences in many different pathogenic pathways and understanding of the origin of autoimmune diseases.