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ID PMID Title PublicationDate abstract
31870059 [Curative effect analysis of ipsilateral total knee and hip arthroplasty at stage I]. 2019 Nov 25 OBJECTIVE: To explore clinical results of ipsilateral total knee and hip arthroplasty at stage I for the treatment of ipsilateral hip and knee diseases. METHODS: From January 2008 to September 2016, 7 patients with ipsilateral knee and hip disease were treated by simultaneous total knee and hip arthroplasty at stage I, including 4 males and 3 females aged from 47 to 68 years old, the courses of disease ranged from 6 to 29 years; 3 patients with rheumatoid arthritis, 3 patients with ankylosing spondylitis, and 1 patient with senile hip and knee arthritis. Operation time, intraoperative blood loss and local wounds during hospitalization were observed and recorded, and Harris hip score and HSS knee score were used to evaluate therapeutic effects. RESULTS: Seven patients were followed up from 6 to 24 months, operative time ranged from 297 to 362 min, blood loss ranged from 300 to 780 ml. Harris hip score before operation ranged from 27.67 to 39.11, 75.32 to 85.10 at 6 months after operation; 3 patients were good and 4 patients moderate. HSS knee score before operation ranged from 40.90 to 51.36, and 73.56 to 85.33 at 6 months after operation; 1 patients were excellent and 6 patients good. No periprosthetic fracture, aseptic loosening and periprosthetic infection occurred in 7 patients. CONCLUSIONS: Ipsilateral total knee and hip arthroplasty at stage I for the treatment of hip and knee disease could restore hip and knee function as soon as possible and recover function of hip and knee to the maximum degree, make patients get down the bed earlier, effectively reduce the complications caused by long-term bedridden, and improve patient's quality and satisfaction of life. While the quality of double-joint arthroplasty at stage I need higher technical requirements which should strengthen the management of the perioperative period, and strictly grasped indications.
31323333 Cardiovascular profile in osteoarthritis: a meta-analysis of cardiovascular events and ris 2019 Nov INTRODUCTION: Higher cardiovascular risk found in rheumatoid arthritis or psoriatic arthritis is largely due to systemic inflammation. In osteoarthritis (OA), occurrence of systemic inflammation has already been sometimes reported, but the possible association between OA and increased cardiovascular risk remains unclear. In this meta-analysis, we aimed to assess the incidences of myocardial infarction (MI) and stroke, and the cardiovascular risk factors in OA patients. METHODS: We searched PubMed, EMBase, and the Cochrane Library to find references of interest up to June 2018. MI and stroke incidence were calculated using meta-proportion analysis. Differences in cardiovascular risk factors between OA patients and controls were expressed as standardized mean differences using the inverse of variance method. RESULTS: The reviewed studies reported 227 MIs in 3550 OA patients (incidence, 7.5%; 95% CI: 3.0-13.8%) and 616 MIs among 12,444 control subjects (incidence, 6.0%; 95% CI: 2.8-10.3%). Meta-analysis of the three longitudinal studies revealed a significantly increased MI risk among OA patients (RR=1.22; 95% CI: 1.02-1.45). We also found a significantly increased stroke risk in OA patients (RR=1.43; 95% CI: 1.38-1.48). Concerning cardiovascular risk factors, OA patients exhibited a pro-atherogenic lipid and glycemic profile including high levels of fasting glucose, total cholesterol, and LDL cholesterol and a high body mass index. Concerning atherosclerosis markers, OA patients exhibited a higher risk of metabolic syndrome, and increased pulse wave velocity. CONCLUSION: Our meta-analysis results revealed higher cardiovascular risk in OA patients. This highlights the importance of cardiovascular risk factor management in OA.
31699619 [Methotrexate in juvenile idiopathic arthritis. Adverse effects and associated factors]. 2020 Mar INTRODUCTION: Methotrexate (MTX) is the drug of choice for juvenile idiopathic arthritis. Its clinical efficacy is limited due to the development of adverse effects (AEs). PATIENTS AND METHODS: A retrospective observational study was conducted on the AEs associated with MTX therapy in children diagnosed with juvenile idiopathic arthritis followed-up in a tertiary hospital between 2008 and 2016. RESULTS: The study included a total of 107 patients, of whom 71 (66.3%) were girls (66.3%). The median age at diagnosis was 6.4 years (IQR 3.1-12.4), with a median follow-up of 45.7 months (IQR 28.8-92.4). There were 48 patients (44.9%) with oligoarthritis, and 26 children (24.3%) with rheumatoid-factor negative polyarthritis. Of these, 52/107 (48.6%) developed AEs, with the most frequent being gastrointestinal symptoms (35.6%) and behavioural problems (35.6%). An age older than 6 years at the beginning of therapy increased the risk of developing AEs, both in the univariate (OR=3.5; 95% CI: 1.5-7.3) and multivariate (12% increase per year) analyses. The doses used, administration route, or International League of Associations for Rheumatology (ILAR) classification, were not associated with the development of AEs. Twenty children required a dosage or route of administration modification, which resolved the AE in 11 (55%) cases. MTX was interrupted due to the development of AEs in 37/107 patients (34.6%), mainly due to increased plasma transaminases (n=14, 37.8%), gastrointestinal symptoms (n=9, 24.3%) and behavioural problems (n=6, 16.3%). CONCLUSIONS: MTX is the therapy of choice for patients with juvenile idiopathic arthritis, but 50% of the children develop some form of AE. Although the AEs are not severe, they lead to interruption of therapy in 35% of the children.
31661985 Autoantigen-specific B cells and plasma cells are prominent in areas of fatty infiltration 2019 Nov Salivary and lacrimal gland involvement is a characteristic feature of primary Sjögren's syndrome (pSS), where tissue destruction is mediated by mononuclear cell infiltration, resulting in lacrimal and salivary gland impairment. We have previously shown distinct prevalence of adipose tissue replacement in the minor salivary gland tissue from pSS patients. The salivary gland microenvironment was further examined through microarray analysis, identifying signalling pathways that promoted adipose tissue development, inflammation, and lymphoma. As B cells may also contribute to disease progression, we now aimed to study the B cell pattern with regard to adipocyte development in pSS. Double immunohistochemical staining of paraffin-embedded salivary gland tissue from 22 pSS patients and 11 non-SS tissue controls was employed, using the characteristic pSS autoantigens Ro52 or Ro60, alongside CD27. Additional CD138/CD20 double staining was also performed to identify the plasma- and general B- cell pattern. Our results demonstrated CD27-positive Ro52 and Ro60 specific cells observed within and in close proximity to the adipose tissue. CD138-positive plasma cells were also seen in areas of adipose tissue replacement, while the CD20(+) cells were located within focal infiltrates, forming distinct B cell zones. The quantification of CD138(+) and CD20(+) cells revealed elevated numbers of CD138(+) cells in areas of fatty infiltration, and also interstitially, in the salivary glands of pSS patients when compared to non-SS controls. A significant increase (p < .01) in CD138(+) cells close to areas of fatty infiltration, and interstitially, with increasing fatty infiltration and focus score was further observed in pSS patients. A correlation between the number of CD20(+) B cell zones/mm(2) of salivary gland tissue and focus score values was also witnessed in the patients (r(2) = 0.6047, p < .001). In conclusion, autoantigen-specific B cells and plasma cells appear prominent in areas of fatty infiltration in salivary glands of pSS patients, where an increase in CD138(+) plasma cells and CD20(+) B cells, in relation to both fatty and focal infiltration, suggests their active involvement in promoting inflammation. Further studies are needed to assess whether these adipocytes are also a result of tissue repair.
31695690 Characterization of cxorf21 Provides Molecular Insight Into Female-Bias Immune Response in 2019 Background: Ninety percent of systemic lupus erythematosus (SLE) patients are women. X chromosome-dosage increases susceptibility to SLE and primary Sjögren's syndrome (pSS). Chromosome X open reading frame 21 (CXorf21) escapes X-inactivation and is an SLE risk gene of previously unknown function. We undertook the present study to delineate the function of CXorf21 in the immune system as well as investigate a potential role in the sex bias of SLE and pSS. Methods: Western blot protein analysis, qPCR, BioPlex cytokine immunoassay, pHrodo™ assays, as well as in vitro CRISPR-Cas9 knockdown experiments were employed to delineate the role of CXorf21 in relevant immunocytes. Results: Expressed in monocytes and B cells, CXorf21 basal Mrna, and protein expression levels are elevated in female primary monocytes, B cells, and EBV-transformed B cells compared to male cells. We also found CXorf21 mRNA and protein expression is higher in both male and female cells from SLE patients compared to control subjects. TLR7 ligation increased CXorf21 protein expression and CXorf21 knockdown abrogated TLR7-driven increased IFNA1 mRNA expression, and reduced secretion of both TNF-alpha and IL-6 in healthy female monocytes. Similarly, we found increased pH in the lysosomes of CXorf21-deficient female monocytes. Conclusion: CXorf21 is more highly expressed in female compared to male cells and is involved in a sexually dimorphic response to TLR7 activation. In addition, CXorf21 expression regulates lysosomal pH in a sexually dimorphic manner. Thus, sexually dimorphic expression of CXorf21 skews cellular immune responses in manner consistent with expected properties of a mediator of the X chromosome dose risk in SLE and pSS.
31641939 Regulation of JAK/STAT signal pathway by miR-21 in the pathogenesis of juvenile idiopathic 2020 Oct BACKGROUND: Overexpression of the components of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is the key factor of the pathogenic mechanisms underlying systemic juvenile idiopathic arthritis (sJIA). The study aims to investigate the association between miR-21 and the JAK/STAT signal pathway in JIA. METHODS: Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) in active JIA patients. The relative expressions of miR-21, STAT3 and suppressor of cytokine signalling 3 in PBMCs were measured by real-time polymerase chain reaction and their expressions were measured by western blotting and dual-luciferase reported assay. Rheumatoid arthritis fibroblast-like synovial cell (RASF) was stimulated to become to osteoclasts using macrophage colony-stimulating factor (M-CSF) and factors that can impact on their differentiation ability were identified through the transfection of LV3-miR-21. The expression of STAT3/p-STAT3 was measured by western blot, and the levels of interleukin (IL)-17A, p65, matrix metalloproteinases (MMP)-3, MMP-4 and receptor activator of nuclear factor-κB after the LV3-miR-21 transfection were tested by enzyme-linked immunosorbent assay. Finally, the miR-21 targeted STAT3 gene was detected by the dual-luciferase reported assay. RESULTS: The expression of miR-21 was significantly lower in JIA patients than in healthy control (P < 0.05). The level of STAT3 was increased in PBMCs of JIA group compared with control group (P < 0.05). Furthermore, the expression levels of miR-21 in sJIA and polyarticular JIA groups were negatively correlated with STAT3 (r = - 0.5854/r = - 0.6134, P < 0.05). The expression of STAT3 changed little in PBMCS after the stimulation of IL-6 and not in RASFs with transfection of LV3-miR-21. The expression of p-STAT3 decreased after the stimulation of IL-6 in RASFs transfected by LV3-miR-21 (P < 0.05). RASFs were induced into osteoclasts using M-CSF. The number of osteoclasts as determined by tartrate-resistant acid phosphatase staining was significantly lower in group miR-21 mimics as compared with the negative control group (P < 0.05). CONCLUSIONS: We showed that expression of miR-21 was significantly lower in JIA patients compared with healthy control. MiR-21 might affect the JAK/STAT signal pathway by suppressing the expression of STAT3 and phosphorylation of STAT3. MiR-21 could inhibit the production of osteoclasts induced from RASFs by M-CSF.
31095909 Berunda Polypeptides: Biheaded Rapamycin Carriers for Subcutaneous Treatment of Autoimmune 2019 Jul 1 The USFDA-approved immunosuppressive drug rapamycin (Rapa), despite its potency, is limited by poor bioavailability and a narrow therapeutic index. In this study, we sought to improve bioavailability of Rapa with subcutaneous (SC) administration and to test its therapeutic feasibility and practicality in a murine model of Sjögren's syndrome (SS), a systemic autoimmune disease with no approved therapies. To improve its therapeutic index, we formulated Rapa with a carrier termed FAF, a fusion of the human cytosolic FK506-binding protein 12 (FKBP12) and an elastin-like polypeptide (ELP). The resulting 97 kDa FAF (i) has minimal burst release, (ii) is "humanized", (iii) is biodegradable, (iv) solubilizes two Rapa per FAF, and (v) avoids organic solvents or amphiphilic carriers. Demonstrating high stability, FAF remained soluble and monodisperse with a hydrodynamic radius of 8 nm at physiological temperature. A complete pharmacokinetic (PK) analysis of FAF revealed that the bioavailability of SC FAF was 60%, with significantly higher blood concentration during the elimination phase compared to IV FAF. The plasma concentration of Rapa delivered by FAF was 8-fold higher with a significantly increased plasma-to-whole blood ratio relative to free Rapa, 24 h after injection. To evaluate therapeutic effects, FAF-Rapa was administered SC every other day for 2 weeks to male non-obese diabetic (NOD) mice, which develop an SS-like autoimmune-mediated lacrimal gland (LG) inflammation and other characteristic features of SS. Both FAF-Rapa and free Rapa exhibited immunomodulatory effects by significantly suppressing lymphocytic infiltration, gene expression of IFN-γ, MHC II, type I collagen and IL-12a, and cathepsin S (CTSS) activity in LG compared to controls. Serum chemistry and histopathological analyses in major organs revealed no apparent toxicity of FAF-Rapa. Given its improved PK and equipotent therapeutic efficacy compared to free Rapa, FAF-Rapa is of further interest for systemic treatments for autoimmune diseases like SS.
31816084 Frequency and distribution of various rheumatic disorders associated with checkpoint inhib 2019 Dec 1 Immune checkpoint inhibitors have advanced the treatment paradigm of various cancers, achieving remarkable survival benefits. However, a myriad of immune-related adverse events (irAE) has been recognized in almost every organ system, presumably because of persistent immune system activation. Rheumatic symptoms such as arthralgia or myalgia are very common. More specific irAE are increasingly being reported. The most frequent ones are inflammatory arthritis, polymyalgia-like syndromes, myositis and sicca manifestations. These rheumatic irAE can develop in ∼5-10% of patients treated with immune checkpoint inhibitors, although true incidence rates cannot be estimated given the lack of prospective cohort studies, and likely underreporting of rheumatic irAE in oncology trials. In this review, we will provide a summary of the epidemiologic data reported for these rheumatic irAE, until more robust prospective longitudinal studies become available to further define the true incidence rate of rheumatic irAE in patients receiving these novel cancer therapies.
30784921 Opuntioside, opuntiol and its metallic nanoparticles attenuate adjuvant-induced arthritis: 2019 Apr Rheumatoid arthritis (RA) is a chronic autoimmune disease of synovial inflammation and joint destruction. This study reports anti-arthritic potential of opuntioside-I opuntiol, and its gold and silver nanoparticles (NPs) against Complete Freund's Adjuvant (CFA)-induced arthritic rats. The mechanistic studies were performed targeting TLRs (TLR-2 and TLR-4) and cytokines (IL-1β and TNF-α) expressions to validate their anti-inflammatory and immuno-modulatory response. The nano-formulations were successfully characterized employing Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) analysis. Opuntiol and opuntioside (OP and OPG: 10, 50 and 100 mg/kg) and opuntiol-coated silver and gold NPs (OP-AgNPs and OP-AuNPs: 0.5, 1 and 3 mg/kg) treatments in arthritic rat have shown minimal arthritic score exhibiting mild to moderate articular changes and tissue swelling in ankle joints. Radiographic examination reveals significant reduction in synovitis with improvement in joints degenarative changes in the presence of aforementioned treatments. Likewise, histology of rat ankle joints depicted comparatively lesser influx of inflammatory cells and diminished granulamatous inflammation. Moreover, treatment groups suppressed protein and mRNA expressions of TLRs (TLR-2 and TLR-4) and cytokines (IL-1β and TNF-α) levels were also significantly declined in the presence of OPG, OP and its NPs comparing to arthritic control. This investigation concludes, the tested compounds and nano-formulations successfully restored the disease progression in CFA-induced arthritic rat owing to their immunomodulatory and anti-inflammatory potentials and can be considered for RA targeted therapy to address the utmost challenges of the disease.
31345742 Disseminated cryptococcosis with granuloma formation in idiopathic CD4 lymphocytopenia. 2020 Feb Idiopathic CD4 lymphocytopenia (ICL) is a rare disease characterized by marked loss of CD4 T-cells without human immunodeficiency virus infection. CD4 T-cells play an important role in granuloma formation in cryptococcal infection. Thus far, among ICL patients, it has not been concluded definitely whether granuloma is formed or not. We report the case of a 39-year-old woman with ICL and disseminated cryptococcal infection with granuloma formation. She was referred to our department because of a lung mass, osteolytic lesion, and a subcutaneous mass identified on a computed tomography scan, and an elevated C-reactive protein level. Cryptococcus neoformans was isolated from the tissues. She also had marked CD4 lymphocytopenia (33 cells/μL), without human immunodeficiency virus infection. In a biopsy specimen of the lung mass, granulomas containing CD4 T-cells were observed. The cryptococcosis was treated with liposomal amphotericin B followed by fluconazole and she was found to be cured. The CD4 T-cell count was persistently low. This case showed that granulomas containing CD4 T-cells can be formed in ICL patients with cryptococcal infection despite very low CD4 T-cell counts.
31998129 Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteocla 2019 Postmenopausal osteoporosis (PMOP) is a metabolic bone disease characterized by decreased bone density and strength due to the imbalance between osteogenesis and osteoclastogenesis. Postmenopausal estrogen withdrawal increases proinflammatory cytokines and increases the serum level of Receptor activator of NF-kB ligand (RANKL)/Osteoprotegerin (OPG), which then leads to the overactivation of osteoclastogenesis. Tetrandrine, a bis-benzylisoquinoline alkaloid, has been widely used in the treatment of rheumatoid arthritis clinically in China. Here, we demonstrate that tetrandrine significantly prevented ovariectomy-induced bone loss and inhibited RANKL-induced osteoclastogenesis. In vivo, we found that intraperitoneal injection of tetrandrine (30 mg/kg) every other day markedly reduced bone loss in ovariectomized mice and the serum levels of TRAcp5b, TNF-a, IL-6, CTX-I, and RANKL/OPG were significantly decreased. In vitro, we found that tetrandrine significantly inhibited osteoclast differentiation in bone marrow monocytes (BMMs) and RAW264.7 cells according to the results of osteoclastogenesis-related gene expression, tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption assay. Mechanistically, tetrandrine inhibited RANKL-induced osteoclastogenesis by suppressing NF-kB, Ca2(+), PI3K/AKT, and MAPKs signaling pathways. Taken together, our findings suggest that tetrandrine suppresses osteoclastogenesis through modulation of multiple pathways and has potential value as a therapeutic agent for PMOP, especially for those suffering from RA and PMOP at the same time.
31890337 Analytical methodologies for determination of methotrexate and its metabolites in pharmace 2019 Dec Methotrexate (MTX) is a folate antagonist drug used for several diseases, such as cancers, various malignancies, rheumatoid arthritis (RA) and inflammatory bowel disease. Due to its structural features, including the presence of two carboxylic acid groups and its low native fluorescence, there are some challenges to develop analytical methods for its determination. MTX is metabolized to 7-hydroxymethotrexate (7-OH-MTX), 2,4-diamino-N10-methylpteroic acid (DAMPA), and the active MTX polyglutamates (MTXPGs) in the liver, intestine, and red blood cells (RBCs), respectively. Additionally, the drug has a narrow therapeutic range; hence, its therapeutic drug monitoring (TDM) is necessary to regulate the pharmacokinetics of the drug and to decrease the risk of toxicity. Due to environmental toxicity of MTX; its sensitive, fast and low cost determination in workplace environments is of great interest. A large number of methodologies including high performance liquid chromatography equipped with UV-visible, fluorescence, or electrochemical detection, liquid chromatography-mass spectroscopy, capillary electrophoresis, UV-visible spectrophotometry, and electrochemical methods have been developed for the quantitation of MTX and its metabolites in pharmaceutical, biological, and environmental samples. This paper will attempt to review several published methodologies and the instrumental conditions, which have been applied to measure MTX and its metabolites within the last decade.
31881715 Biological Applications of Thiocarbohydrazones and Their Metal Complexes: A Perspective Re 2019 Dec 25 Although organic compounds account for more than 99% of currently approved clinical drugs, the established clinical use of cisplatin in cancer or auranofin in rheumatoid arthritis have paved the way to several research initiatives to identify metal-based drugs for a wide range of human diseases. Nitrogen and sulfur donor ligands, characterized by different binding motifs, have been the subject in recent years of one of the main research areas in coordination chemistry. Among the nitrogen/sulfur compounds, very little is known about thiocarbohydrazones (TCH), the higher homologues of the well-known thiosemicarbazones (TSC), and their metal complexes. The extra hydrazine moiety provides the ligands of variable metal binding modes, structural diversity and promising biological implications. The interesting coordination chemistry of TCH has mainly been focused on symmetric derivatives, which are relatively simple to synthesize while few examples of asymmetric ligands have been reported. This informative review on TCHs and their metal complexes will be helpful for improving the design of metal-based pharmaceuticals for applications ranging from anticancer to antinfective therapy.
31776035 A review on anti-inflammatory activity of green synthesized zinc oxide nanoparticle: Mecha 2020 Jan Inflammation plays a very important role in the pathogenesis of various diseases like atherosclerosis, rheumatoid arthritis, asthma, and cancer. Lack of anti-inflammatory drugs and vectors provokes the need for developing new molecules for the management of inflammatory disorders. Nanotechnology has emerged as a wonderful research area in the past decade owing to its enhanced properties than bulk counterparts. This paper discusses the green synthesis of zinc oxide nanoparticle (ZnO NPs) and various characterization tools employed to comprehend the physiochemical properties of nanoparticles. ZnO NPs interaction with cells and its pharmacokinetic behavior inside the cells has also been discussed. The anti-inflammatory activity of ZnO NPs has been elucidated with the mechanism-based approach. A concise literature review has been included which summarizes the size, shape of ZnO NPs and the inflammatory model used for analyzing the anti-inflammatory activity of ZnO NPs. ZnO NPs potential offering towards anti-inflammatory activity like stable nature, selective targeting has been discussed briefly. The present study highlights the potential of ZnO NPs as an anti-inflammatory drug molecule or a vector for drug delivery.
31736479 An Ex Vivo Tissue Culture Model of Cartilage Remodeling in Bovine Knee Explants. 2019 Nov 3 Ex vivo culture systems cover a broad range of experiments dedicated to studying tissue and cellular function in a native setting. Cartilage is a unique tissue important for proper function of the synovial joint and is constituted by a dense extracellular matrix (ECM), rich in proteoglycan and type II collagen. Chondrocytes are the only cell type present within cartilage and are widespread and relatively low in number. Altered external stimuli and cellular signalling can lead to changes in ECM composition and deterioration, which are important pathological hallmarks in diseases such as osteoarthritis (OA) and rheumatoid arthritis. Ex vivo cartilage models allow 1) profiling of chondrocyte mediated alterations of cartilage tissue turnover, 2) visualizing the cartilage ECM composition, and 3) chondrocyte rearrangement directly in the tissue. Profiling these alterations in response to stimuli or treatments are of high importance in various aspects of cartilage biology, and complement in vitro experiments in isolated chondrocytes, or more complex models in live animals where experimental conditions are more difficult to control. Cartilage explants present a translational and easily accessible method for assessing tissue remodeling in the cartilage ECM in controllable settings. Here, we describe a protocol for isolating and culturing live bovine cartilage explants. The method uses tissue from the bovine knee, which is easily accessible from the local butchery. Both explants and conditioned culture medium can be analyzed to investigate tissue turnover, ECM composition, and chondrocyte function, thus profiling ECM modulation.
31511872 Post-transcriptional regulation of inflammation by RNA-binding proteins via cis-elements o 2019 Nov 1 In human genome, there are approximately 1,500 RNA-binding proteins (RBPs). They can regulate mRNA stability or translational efficiency via ribosomes and these processes are known as 'post-transcriptional regulation'. Accumulating evidences indicate that post-transcriptional regulation is the determinant of the accurate levels of cytokines mRNAs. While transcriptional regulation of cytokines mRNAs has been well studied and found to be important for the rapid induction of mRNA and regulation of the acute phase of inflammation, post-transcriptional regulation by RBPs is essential for resolving inflammation in the later phase, and their dysfunction may lead to severe autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus. For post-transcriptional regulation, RBPs recognize and directly bind to cis-regulatory elements in 3' untranslated region of mRNAs such as AU-rich or constitutive decay elements and play various roles. In this review, we summarize the recent findings regarding the role of RBPs in the regulation of inflammation.
31498665 Systemic sclerosis. 2019 Sep 2 Systemic sclerosis is a complex autoimmune connective tissue disease which carries a significant burden of disease-related morbidity including potentially life-threatening complications. Systemic sclerosis can affect all the major organs and therefore, although the disease is uncommon, many hospital-based specialists are involved in patient care. Vascular disease (e.g. Raynaud's phenomenon) is an almost universal symptom in patients with systemic sclerosis and is often the earliest manifestation of the disease. Systemic sclerosis not uncommonly can overlap with other rheumatological conditions (e.g. rheumatoid arthritis and myositis). During the past few decades there have been major advances in understanding the pathogenesis of systemic sclerosis and these are driving advances in treatment. There are now a number of effective treatments to manage many of the different organ-based complications. Autologous haemopoietic stem cell transplantation is a potential treatment option in highly selected patients. This review updates the clinician about epidemiology, pathogenesis, differential diagnosis, the wide clinical spectrum of disease, and current and emerging treatments for systemic sclerosis.
31365389 Clustering of immune-mediated diseases in sarcoidosis. 2019 Sep PURPOSE OF REVIEW: Sarcoidosis is an immune-mediated disease of unknown cause. Immune-mediated diseases appear to cluster in patients and in families. We review what is known on this topic for sarcoidosis, and what factors may underlie disease clustering. RECENT FINDINGS: In populations of patients with sarcoidosis, relative risk estimates of Sjögren's syndrome, systemic lupus erythematosus, autoimmune hepatitis, ankylosing spondylitis, multiple sclerosis (MS), celiac disease, autoimmune thyroid disease, and ulcerative colitis, varied between 2.1 and 11.6. In relatives of patients with sarcoidosis, relative risk estimates varied between 1.3 and 5.8 for sarcoidosis, MS, celiac disease, type 1 diabetes, Graves' disease, rheumatoid arthritis, Crohn's disease, and ulcerative colitis. Shared risk loci in key immunological pathways provide evidence for a contribution to development of multiple diseases. Identical changes in the immune status, epigenetic alterations, and environmental triggers have been detected in several diseases, and drug-induced disease is likely responsible for a small portion of co-occurring disease. SUMMARY: Clustering of sarcoidosis and other immune-mediated diseases in patients and in their relatives occurs for sarcoidosis, MS, celiac disease, Graves' disease, and ulcerative colitis. Further research is needed to substantiate causal links and risk estimates in patients and their relatives.
31292397 Synchronous Occurrence of Bazex Syndrome and Remitting Seronegative Symmetrical Synovitis 2019 Nov 15 A 69-year-old man developed bilateral polyarthritis, edematous extremities, and skin desquamation on the fingers and ears. He did not meet the criteria for any connective tissue disease, including rheumatoid arthritis. An examination revealed advanced lung cancer. His systemic manifestations were attributed to paraneoplastic Bazex syndrome and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Treatment with pembrolizumab (an anti-programmed death-1 antibody) for lung cancer relieved his symptoms and shrank the lung tumor. Bazex and RS3PE syndromes are rare paraneoplastic diseases. We herein report this unique case of synchronous development of these two paraneoplastic syndromes in the presence of advanced lung cancer.
31261552 The incidence of spondyloarthritis in Slovenia. 2019 Jun Epidemiological studies of spondyloarthritides (SpA) are rare and data for our country are lacking. We aimed to determine the incidence of SpA in a well-defined region in Slovenia.We performed a retrospective chart review of adults diagnosed with SpA between January 2014 and December 2016 at an integrated secondary/tertiary medical center, which provides rheumatology services to almost a half of the adult national population, that is, 700,000 adults. Potential cases were ascertained by searching the electronic medical records for ICD-10 codes M02, M07, M13, M45, M 46.1, K50, K51, and L40. SpA cases were stratified as axial and peripheral SpA and then the annual incidence rates of SpA overall and both subsets were estimated.During the 3-year period we identified 302 SpA cases (55.0% males, median [interquartile range] age 46.7 [35.0-57.5] years). 98 (32.5%) of them had predominantly axial SpA and the remainder peripheral SpA. The estimated annual incidence rate per 100,000 adults in our region was 14.3 (95% confidence interval [CI] 12.8-16.0) for SpA overall, 4.6 (95% CI 3.8-5.6) for axial SpA, and 9.6 (95% CI 8.4-11.1) for peripheral SpA.The estimated annual incidence rate of 14.3 cases per 100,000 adults in SpA overall was comparable to that of rheumatoid arthritis in our population. The peripheral SpA was twice as common as axial SpA.