Reconstruction and analysis of the lncRNA–miRNA–mRNA network based on competitive endogenous RNA reveal functional lncRNAs in rheumatoid arthritis

2017 ◽  
Vol 13 (6) ◽  
pp. 1182-1192 ◽  
Author(s):  
Hui Jiang ◽  
Rong Ma ◽  
Shubiao Zou ◽  
Yongzhong Wang ◽  
Zhuqing Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Disease ◽  
General Population ◽  
Unknown Etiology ◽  
Competitive Endogenous Rna

Rheumatoid arthritis (RA) is an autoimmune disease with an unknown etiology, occurring in approximately 1.0% of general population.

scholarly journals Specificity of Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis

Antibodies ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 37 ◽  
Author(s):  
Nicole H. Trier ◽  
Bettina E. Holm ◽  
Paul R. Hansen ◽  
Ole Slot ◽  
Henning Locht ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Amino Acids ◽  
Autoimmune Disease ◽  
Unknown Etiology ◽  
Specific Nature ◽  
Citrullinated Protein ◽  
Disease Specific

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. The majority of individuals with RA are positive for the disease-specific anti-citrullinated protein antibodies (ACPAs). These antibodies are primarily of cross-reactive nature, hence, the true autoantigen to ACPA remains unidentified. In this study, we analyzed the reactivity of RA sera to several post-translationally modified epitopes, in order to further characterize the specific nature of ACPAs by immunoassays. Substituting citrulline with other amino acids, e.g., D-citrulline, homo-citrulline and methyl-arginine illustrated that ACPAs are utmost specific for citrullinated targets. Collectively, these findings support that ACPAs and citrullinated targets are specific for RA, making citrulline-containing peptide targets the most effective assays for detection of ACPAs.

scholarly journals Rheumatoid Arthritis-Associated Mechanisms of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans

2019 ◽  
Vol 8 (9) ◽  
pp. 1309 ◽  
Author(s):  
Eduardo Gómez-Bañuelos ◽  
Amarshi Mukherjee ◽  
Erika Darrah ◽  
Felipe Andrade
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Disease ◽  
Porphyromonas Gingivalis ◽  
Aggregatibacter Actinomycetemcomitans ◽  
Unknown Etiology ◽  
Preventive Interventions ◽  
Periodontal Pathogens ◽  
Periodontal Bacteria ◽  
Immune Mediated

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology characterized by immune-mediated damage of synovial joints and antibodies to citrullinated antigens. Periodontal disease, a bacterial-induced inflammatory disease of the periodontium, is commonly observed in RA and has implicated periodontal pathogens as potential triggers of the disease. In particular, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans have gained interest as microbial candidates involved in RA pathogenesis by inducing the production of citrullinated antigens. Here, we will discuss the clinical and mechanistic evidence surrounding the role of these periodontal bacteria in RA pathogenesis, which highlights a key area for the treatment and preventive interventions in RA.

Novel Nano Carriers for the Treatment of Progressive Auto Immune Disease Rheumatoid Arthritis

2020 ◽  
Vol 26 ◽  
Author(s):  
Ritu Mishra ◽  
Swati Gupta
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Autoimmune Disease ◽  
Drug Delivery Systems ◽  
Clinical Manifestations ◽  
Adaptive Immune Response ◽  
Delivery Systems ◽  
Current Therapy ◽  
Genetic And Environmental Factors ◽  
Novel Drug

Background: Rheumatoid arthritis (RA) is the most common occurring progressive, autoimmune disease, affecting 1% of the population and the ratio of affected women is three times as compared to men in most developing countries. Clinical manifestations of RA are the presence of anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) in blood, tendered joints and soreness of the muscles. Some other factors which may lead to chronic inflammation are genetic and environmental factors as well as adaptive immune response. Several conventional drugs are available for the treatment of RA but have their own drawbacks which can be overcome by the use of novel drug delivery systems. : The objective of the present review is to focus on the molecular pathogenesis of the disease and its current conventional treatment with special reference to the role of novel drug delivery systems encapsulating anti rheumatic drugs and herbal drugs in passive and receptor mediated active targeting against RA. On reviewing the conventional and current therapeutics agains RA, we conclude that, although the current therapy for the treatment of RA is capable enough, yet more advances in the field of targeted drug delivery will sanguinely result in effective and appropriate treatment of this autoimmune disease.

Evaluation of Serum Calprotectin Level and Disease Activity in Patients with Rheumatoid Arthritis

2019 ◽  
Vol 15 (4) ◽  
pp. 316-320
Author(s):  
Mir Amir Aghdashi ◽  
Seyedmostafa Seyedmardani ◽  
Sholeh Ghasemi ◽  
Zohre Khodamoradi
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Arthritis ◽  
Unknown Etiology ◽  
Tender Joint Count ◽  
Serum Samples ◽  
Tender Joint ◽  
Cross Sectional ◽  
Calprotectin Level ◽  
Remission Phase

Background: Rheumatoid Arthritis (RA) is the most common type of chronic inflammatory arthritis with unknown etiology marked by a symmetric, peripheral polyarthritis. Calprotectin also can be used as a biomarker of disease activity in inflammatory arthritis and other autoimmune diseases. Objective: In this study, we evaluated the association between serum calprotectin level and severity of RA activity. Methods: A cross-sectional study was conducted on 44 RA patients with disease flare-up. Serum samples were obtained from all patients to measure calprotectin, ESR, CRP prior to starting the treatment and after treatment period in the remission phase. Based on Disease Activity Score 28 (DAS28), disease activity was calculated. Results: Of 44 RA patients, 9(20.5%) were male and 35(79.5%) were female. The mean age of our cases was 53±1.6 years. Seventeen (38.6%) patients had moderate DAS28 and 27(61.4%) had high DAS28. The average level of calprotectin in the flare-up phase was 347.12±203.60 ng/ml and 188.04±23.58 ng/ml in the remission phase. We did not find any significant association between calprotectin and tender joint count (TJC; P=0.22), swollen joint count (SJC; P=0.87), and general health (GH; P=0.59), whereas significant associations were found between the calprotectin level and ESR (p=0.001) and DAS28 (p=0.02). The average calprotectin level in moderate DAS28 (275.21±217.96 ng/ml) was significantly lower than that in high DAS28 (392.4±183.88 ng/ml) (p=0.05). Conclusion: We showed that the serum level of calprotectin can be a useful and reliable biomarker in RA activity and its severity. It also can predict treatment response.

scholarly journals Solar Radiation and Vitamin D: Mitigating Environmental Factors in Autoimmune Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Gerry K. Schwalfenberg
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Inflammatory Bowel Disease ◽  
Vitamin D ◽  
Type 1 Diabetes ◽  
Autoimmune Disease ◽  
Solar Radiation ◽  
Inflammatory Bowel

This paper looks at the environmental role of vitamin D and solar radiation as risk reduction factors in autoimmune disease. Five diseases are considered: multiple sclerosis, type 1 diabetes, rheumatoid arthritis, autoimmune disease of the thyroid, and inflammatory bowel disease. Clinical relevant studies and factors that may indicate evidence that autoimmune disease is a vitamin D-sensitive disease are presented. Studies that have resulted in prevention or amelioration of some autoimmune disease are discussed. An example of the utility of supplementing vitamin D in an unusual autoimmune disease, idiopathic thrombocytic purpura, is presented.

scholarly journals AB0533 ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA) IN GENERAL POPULATION WITHOUT ANCA ASSOCIATED VASCULITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1563.3-1563
Author(s):  
H. Tamaki ◽  
S. Fukui ◽  
T. Nakai ◽  
G. Kidoguchi ◽  
S. Kawaai ◽  
...  
Keyword(s):  
Risk Factors ◽  
Autoimmune Disease ◽  
General Population ◽  
Granulomatosis With Polyangiitis ◽  
Dietary Habits ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
Anca Associated Vasculitis ◽  
The Mean

Background:Currently it is hypothesized that many systemic autoimmune diseases occur due to environmental risk factors in addition to genetic risk factors. Anti-Neutrophil Cytoplasmic Antibody (ANCA) is mainly associated with three systemic autoimmune disease including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA). It is known that ANCA can be positive before clinical symptoms in patients with known diagnosis of GPA and ANCA titers rise before clinical manifestations appear. However, prevalence of ANCA among general population is not well known. It has not been described as well how many of people with positive ANCA eventually develop clinical manifestations of ANCA associated Vasculitis.Objectives:This study aims to estimate prevalence of ANCA in general population without ANCA associated Vasculitis. It also describes natural disease course of people with positive ANCA without ANCA associated Vasculitis. Risk factors for positive ANCA are also analyzed.Methods:This is a single center retrospective study at Center for Preventive Medicine of St. Luke’s International Hospital in Tokyo. ANCA was checked among the patients who wished to between 2018 and 2019. St. Luke’s Health Check-up Database (SLHCD) was utilized to collect the data. The patients whose serum was measured for ANCA were identified. The data for basic demographics, social habits, dietary habits and laboratory data were extracted. The charts of the patients with positive ANCA were reviewed.Results:Sera of total 1204 people were checked for ANCA. Of these 1204 people, 587 (48.8%) are male and the mean age was 55.8 years (32.6 to 79). There were total 11 patients with positive ANCA. Myeloperoxidase ANCA (MPO-ANCA) was positive for 3 patients and proteinase 3 ANCA (PR3-ANCA) was positive for 8 patients. Of these 11 patients, 5 were male (45.5%) and the mean age was 54.6 years. Two patients had history of autoimmune disease (primary biliary cirrhosis and ulcerative colitis). Five patients were evaluated by rheumatologists with the median follow-up period of 274 days. None of them developed clinical signs and symptoms of ANCA associated Vasculitis. Four out of five patients had ANCA checked later, two of which turned negative. The prevalence of ANCA in this cohort was 0.9% (95% confidence interval [95% CI]: 0.5% to 1.6%). Univariate analysis was performed to identify risk factors of positive ANCA. The variables analyzed include age, gender, body mass index (BMI), smoking habits, alcohol intake, dietary habits (fruits, fish, red meat), hypertension, dyslipidemia, and laboratory data. None of these variables demonstrated statistically significant differences except for positive rheumatoid factor (ANCA positive group: 33 % vs ANCA negative group: 9.1%, p value = 0.044).Conclusion:The prevalence of ANCA in this cohort was 0.9% (95% CI: 0.5% to 1.6%). None of them who had a follow-up developed ANCA associated Vasculitis during the follow-up period. Longer follow-up and more patients are necessary to determine natural course of people with positive ANCA.Disclosure of Interests:None declared

scholarly journals FRI0550 CAN CYTOKINE GENE POLYMORPHISMS BE USEFUL FOR THE THERAPEUTIC CHOICE IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 876.2-877
Author(s):  
S. Tsujimoto ◽  
M. Shigesaka ◽  
A. Tanaka ◽  
Y. Ozaki ◽  
T. Ito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Disease ◽  
Gene Polymorphisms ◽  
Therapeutic Response ◽  
Bone Erosion ◽  
Japanese Patients ◽  
Cartilage Degradation ◽  
Cytokine Gene ◽  
Biological Dmards ◽  
Cytokine Gene Polymorphisms

Background:Rheumatoid arthritis (RA) is a common autoimmune disease. It is characterized by systemic synovitis with bone erosion and joint cartilage degradation(1). Production of autoantibody is important for autoimmune disease. Cytokines play crucial roles in its pathogenesis(2). SNP distribution varies between races. Few studies have examined SNP targeted at Japanese patients. The analysis of cytokine gene polymorphisms is important factor of pathophysiology and treatment.Objectives:This analysis was aimed to investigate the association between cytokine gene polymorphisms and autoantibody and therapeutic response in Japanese RA patients.Methods:This study subjects consisted of 100 RA patients and 50 healthy controls. We extracted data on patient sex, age, disease duration, rheumatoid factor (RF), anti cyclic citrullinated peptide (anti-CCP) antibody and therapeutic response including methotrexate (MTX) and biological DMARDs. Genomic DNA was isolated from peripheral blood, these were genotyped for TNFα, TGFβ1, IL-6, IL-10 and IFNγ polymorphisms. We analyzed these data using a chi-square test.Results:IL-10 (-819 C/T and -592 C/A) revealed that there were significant decrease in the frequency of IL-10 (-819) CC genotype and (-592) CC genotype as compared to controls in RA patients. Genotyping of IL-10 showed that there was significant decrease ACC/ACC genotype (Table 1).IFNγ (+874 A/T) revealed that there was significant decrease in the frequency of TT genotype as compared to controls (Table 1).No significant differences in TNFα, TGFβ1and IL-6 genotypes and alleles frequency were observed between RA patients and control.TGFβ1(+869 A/T) in patients with anti-CCP antibody positive revealed that there was significant decrease in the frequency of TT genotype as compared to patients with anti-CCP antibody negative (Table 2).No significant association between RF and any cytokine gene polymorphism.Analyzing cytokine gene polymorphisms could be useful for treatment with MTX and biological DMARDs.Table 1.Table 2.Conclusion:IL-10 (-819 C/T, -592 C/A) and IFNγ (+874 A/T) polymorphism might be related to RA in Japanese population. In addition, TGFβ1(+869 A/T) polymorphism might be associated with the production of anti-CCP antibody. These results suggest that the analyzing cytokine gene polymorphisms may offer promise as useful factors in the choice of treatment for Japanese RA patients.References:[1] Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010; 376: 1094–108.[2] McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007 Jun;7(6):429-42.Disclosure of Interests:None declared

scholarly journals AB0925-PARE A NARRATIVE REVIEW ASSESSING THE ROLE OF DIETARY SALT AS AN ENVIRONMENTAL RISK FACTOR FOR THE ONSET AND SEVERITY OF RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1484.1-1484
Author(s):  
S. Ahmed ◽  
E. Nikiphorou ◽  
J. Bayliss
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factor ◽  
Autoimmune Disease ◽  
Environmental Risk ◽  
Narrative Review ◽  
Environmental Risk Factor ◽  
T Helper ◽  
Dietary Salt ◽  
Salt Consumption

Background:The role of dietary salt consumption in the etiopathogenesis of Rheumatoid Arthritis (RA), and autoimmune disease in general, has received renewed interest. This has been fueled by the increased prevalence of autoimmune disease worldwide correlating with western diets and heightened consumption of salt rich foods and also studies at the cellular level demonstrating induction of IL 17 producing T helper cells (Th17) by dietary salt.Objectives:To conduct a narrative review of observational studies and clinical trials on the role of dietary salt as an environmental risk factor for the onset and development of RA.Methods:A comprehensive search was done of the literature from 2010 to 2021, using the search terms dietary salt and RA; the native interfaces EBSCO and Ovid were used. Databases searched included Pubmed, Embase, EMCare, Medline and CINAHL using a Population, Exposure and Outcome framework; the MESH terms RA, risk factors, nutrition and salt were used. Data was extracted by an independent reviewer.Results:Out of the 72 studies initially identified, 50 were included in this review. Studies in murine models have demonstrated that high concentrations of sodium chloride promote the differentiation of T helper lymphocytes, via the serum- and glucocorticoid- inducible kinase 1 (SGK1) mediator towards the proinflammatory Th17 driven immune response. Six studies were carried out in human subjects. Study design ranged from cross sectional observational to nested case control studies. Sodium intake amongst participants characterized as having high intake, or being placed in the higher quartiles, ranged from 4.5-5grams per day. 5 out of 6 studies demonstrated that increased dietary salt consumption is associated with earlier onset RA. One study suggested an association between high salt intake and erosive disease at diagnosis and the development of anti-citrullinated protein antibodies (ACPA), although evidence was weak and from a single study only. Another study found that increased consumption of salt was only associated with risk of RA in smokers, highlighting the need to explore confounding variables further.Conclusion:This narrative review of the literature provides some evidence that supports a role of excess dietary salt consumption as a risk factor for the onset and severity of RA.Disclosure of Interests:None declared

scholarly journals AB0048 ENZYMATIC PATTERN OF CIRCULATING PRO- AND ANTIOXIDANT ENZYMES IN RHEUMATOID ARTHRITIS PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1056.2-1057
Author(s):  
S. Bedina ◽  
E. Mozgovaya ◽  
A. Trofimenko ◽  
S. Spitsina ◽  
M. Mamus
Keyword(s):  
Rheumatoid Arthritis ◽  
Antioxidant Enzymes ◽  
Disease Activity ◽  
Neutrophil Extracellular Traps ◽  
Unknown Etiology ◽  
Antioxidant Enzyme Activities ◽  
Reference Ranges ◽  
Sod Activity ◽  
Low Disease Activity ◽  
Extracellular Traps

Background:Rheumatoid arthritis (RA) is an autoimmune rheumatic disease of unknown etiology characterized by chronic erosive arthritis and systemic organ involvement resulting in early disability and shorter life expectancy. Neutrophils are suggested to play a substantial role in the induction and promotion of autoimmune inflammation in RA. This ability can be based on newly discovered feature of neutrophils to release neutrophil extracellular traps (NETs) during specific type cell death called NETosis. Hyperproduction of reactive oxygen species (ROS) is one of the factors promoting NETs production. With this background, the study of pro- and antioxidant enzymatic activities in RA patients can be of great interest.Objectives:To assess plasma activities of essential prooxidant and antioxidant enzymes in RA patients.Methods:The research was carried out in agreement with the WMA Declaration of Helsinki principles. 71 RA patients (46 women and 25 men) were enrolled in the study. The diagnosis was verified using ACR/EULAR criteria (2010). RA activity was measured using the Disease Activity Score of 28 joints (DAS28). 30 healthy persons comprise control group. Plasma xanthine oxidase (XO; ЕС 1.17.3.2), xanthine dehydrogenase (XDH; ЕС 1.17.1.4) and superoxide dismutase (SOD; ЕС 1.15.1.1) activities were measured using spectrophotometric technique. XO and XDG activities were expressed as nmol/ml/min, SOD activity – as units of action. Statistical analysis was performed using Statistica 6.0 software package. Differences were considered significant when p<0.05. Reference ranges were calculated as means ±2SD.Results:Mean age of patients was 43.2±3.6 years, mean RA duration was 11.9±2.6 years. 24 (33.8%) RA patients had low disease activity, and 6 (8.5%) patients had high one. Extra-articular manifestations were found in 30 (42.2%) patients. 30% of them had cardiovascular involvement, 23.3% – pulmonary lesions, and 23.3% had renal involvement. Reference ranges for XO, XDG, and SOD activities were 2.28-5.12 nmol/min/ml, 3,96-7,24 nmol/min/ml, and 3,13-6,58 units, respectively. We examined activities of these enzymes in circulation of RA patients with different patterns of clinical manifestations as well as relationship between RA activity and XO, XDG, and SOD activities. RA patients had increased both mean XO and mean SOD activities (p<0.001 for both enzymes). XO activity reached its highest values at maximum disease activity and overt extra-articular involvements, while SOD activity did it in moderate and high disease activities as well as in patients with joint manifestations. XDG activity was increased in low disease activity (р<0.001) and solely joint lesions (р=0.011), while moderate or high disease activities (р=0.008) and extra-articular involvements (р=0.025) were characterized by decreased activity of this enzyme.Conclusion:We have revealed substantial multidirectional changes of plasma XO and XDG activities in RA. Plasma enzymatic pattern in RA patients is characterized by activation of both oxidant and antioxidant metabolic pathways. Activities of XO and SOD were positively correlated with RA activity, while XDG activity was negative correlated with RA activity. The differences between selective articular RA type and RA form with extraarticular manifestations were also revealed. Changes in oxidant and antioxidant enzyme activities can be connected with anticitrulline autoimmunity in RA via production of citrulline-rich neutrophil extracellular traps, thus enhancing rheumatoid autoimmunity.Disclosure of Interests:None declared

scholarly journals Mortality rate in rheumatoid arthritis-related interstitial lung disease: the role of radiographic patterns

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maria A. Nieto ◽  
Maria J. Rodriguez-Nieto ◽  
Olga Sanchez-Pernaute ◽  
Fredeswinda Romero-Bueno ◽  
Leticia Leon ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Mortality Rate ◽  
General Population ◽  
Lung Disease ◽  
Interstitial Pneumonia ◽  
Usual Interstitial Pneumonia ◽  
Multiple Regression Model ◽  
Multicentric Study

Abstract Background To assess mortality rate (MR) and standardized mortality rate (SMR) of rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients and to evaluate the role of radiographic patterns in mortality. Methods A longitudinal multicentric study was conducted in RA-ILD patients from 2005 to 2015 and followed-up until October 2018 in Madrid. Patients were included in the Neumologia-Reumatología y Enfermedades Autoinmunes Registry, from diagnosis of ILD. The main outcome was all-cause mortality. The radiographic pattern at baseline [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), or others] was the independent variable. Covariables included sociodemographic and clinical data. Survival techniques were used to estimate MR, expressed per 1000 persons-year with their 95% confidence intervals [CI]. Cox multiple regression model was run to examine the influence of radiographic patterns on survival. SMR [CI] was calculated comparing MR obtained with MR expected in the general population of Madrid by indirect age-gender standardization. Results 47 patients were included with a follow-up 242 patients-year. There were 16 (34%) deaths, and most frequent causes were acute ILD exacerbation and pneumonia. MR was 64.3 [39.4–104.9], and 50% of the patients died at 8.3 years from ILD diagnosis. After adjusting for confounders, (UIP compared to NSIP was associated with higher mortality risk. The overall SMR was 2.57 [1.4–4.17]. Women of 60–75 years of age were the group with the highest SMR. Conclusions RA-ILD is associated with an excess of mortality compared to general population. Our results support that UIP increases the risk of mortality in RA-ILD, regardless other factors.

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