Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 33304142 | Association study of CCR6 rs3093024 with Rheumatoid Arthritis in a Pakistani cohort. | 2020 Dec | C-C Chemokine receptor 6 (CCR6), an important protein in inflammatory and immunological responses, has been previously reported to be associated with rheumatoid arthritis (RA). Therefore, in order to replicate these findings, a case-control study was conducted on 500 subjects (including 250 RA patients and 250 healthy controls) of Pakistani origin. The aim of this study was to determine the association of CCR6 rs3093024 variant with RA and identify its role in splicing events using bioinformatics tools. The clinical and demographic characteristics of the patients were collected using a well-designed questionnaire. The genotype frequencies of CCR6 rs3093024 variant were determined using tetra-primer ARMS-PCR (amplification of refractory mutation system-polymerase chain reaction) method. A significant difference was found between CCR6 rs3093024 genotype frequencies [P = 0.0016, χ (2)  = 12.915]. Similarly, a significant difference in the allele frequencies between RA patients and healthy controls was also observed [P = 0.0003 and OR (95% CI) = 0.63 (0.49-0.80)]. The stratification of patients showed that there was a significant increase in AA genotype against AG + GG in patients [P = 0.0014, OR (95% CI) = 2.0 (1.32-3.02)]. Furthermore, using bioinformatics analysis, it was found that CCR6 rs3093024 variant might create a potential splicing enhancer motif (SF2/ASF (IgM-BRCA1) with score of 77.92; Threshold 70.53), which might have important impact on the product of this gene. This study suggests that the A variant of CCR6 rs3093024 variant is significantly associated with RA-risk and its G variant is protective in Pakistani population but a multi-cohort large sized population study is needed to elucidate these results. Moreover, functional studies are needed to highlight the effects of this polymorphism on the function of CCR6 gene. | |
| 33204418 | Renal dysfunction among rheumatoid arthritis patients: A retrospective cohort study. | 2020 Dec | BACKGROUND: Rheumatoid arthritis (RA) is a common rheumatological disease which can involve a variety of different renal manifestations. This may be explained by disease effect itself or by medications used for treatment that may lead to renal dysfunction and its complications.We aimed to identify the prevalence and factors that played a role in renal dysfunction among RA Jordanian patients. METHOD: 285 patients with RA visiting outpatient clinic between March 2016 and March 2017 were included in a retrospective study design. Age, gender, comorbidities, duration of the disease, medications and laboratory results were gathered and scoring of RA activity was done. RESULTS: Data gathered from the 285 patients showed a female predominance with 88.4% female and 11.6% male. The average disease duration was 6.7 years. Age, DM, HTN, and serum CRP were associated with worse renal function on univariate analysis. 44 patients (18.8%) presented with microscopic hematuria, 16 (6.9%) with proteinuria and only 5 (2.1%) patients presented with both microscopic hematuria and proteinuria. Patients with eGFR <60 ml/min had longer disease duration with a mean of 11 years (±7.7) in comparison to 6.4 years (±6.1) for those with eGFR>90 ml/min (P = 0.001). CONCLUSION: Renal dysfunction is not common in RA Jordanian population and has variable presentations. Age and the duration of illness play a major role in the progression of CKD if present. Future prospective studies evaluating renal biopsies in RA patients are needed. | |
| 33167385 | Causal Inference between Rheumatoid Arthritis and Breast Cancer in East Asian and European | 2020 Nov 5 | Previous studies have been reported that the association between rheumatoid arthritis (RA) and breast cancer remains inconclusive. A two-sample Mendelian randomization (MR) analysis can reveal the potential causal association between exposure and outcome. A two-sample MR analysis using the penalized robust inverse variance weighted (PRIVW) method was performed to analyze the association between RA and breast cancer risk based on the summary statistics of six genome-wide association studies (GWAS) targeting RA in an East Asian population along with summary statistics of the BioBank Japan (BBJ), Breast Cancer Association Consortium (BCAC), and Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) targeting breast cancer. We found that the direction of the effect of RA on breast cancer varied among GWAS-summary data from BBJ, BCAC, and CIMBA. Significant horizontal pleiotropy based on a penalized robust MR-Egger regression was observed only for BBJ and CIMBA BRCA2 carriers. As the results of the two-sample MR analyses were inconsistent, the causal association between RA and breast cancer was inconclusive. The biological mechanisms explaining the relationship between RA and breast cancer were unclear in Asian as well as in Caucasians. Further studies using large-scale patient cohorts are required for the validation of these results. | |
| 32983932 | Metabolic Syndrome and Atherogenic Indices in Rheumatoid Arthritis and their Relationship | 2020 Jun | BACKGROUND AND OBJECTIVE: Metabolic syndrome (MetS), a constellation of metabolic abnormalities including hypertension, obesity, glucose intolerance, and dyslipidemia, is highly prevalent in patients with rheumatoid arthritis (RA). Our aim was to assess the magnitude of MetS and its determinants in RA patients and to evaluate different atherogenic indices that are reflective of the risk for future cardiovascular disease. PATIENTS AND METHODS: The study was conducted on 104 RA patients and 103 age- and sex-matched healthy controls. The frequency of MetS was assessed using the guidelines recommended for Asian Indians. RESULTS: A total of 104 RA patients participated with majority being females (85.6%), with a mean age of 43.82 ± 13.32 years. The frequency of MetS in patients with RA (36.5%) was significantly higher than in controls (15.5%). The atherogenic indices were found to be significantly higher in RA patients than controls (P < 0.01). On logistic regression, disease activity score (DAS28) scale for 28 joints and disease duration remained significant independent predictors of the presence of MetS in RA patients (P < 0.01 and 0.05, respectively). CONCLUSIONS: RA is a kind of chronic disease of long course, and MetS and atherogenic indices are often concomitant in these patients. The study showed that the frequency of MetS was higher in patients with RA than in controls, and that DAS28 and disease duration remained significant independent predictors of the presence of MetS in RA patients. | |
| 32766259 | The Role of Vitamin D in Combination Treatment for Patients With Rheumatoid Arthritis. | 2020 | Background: The aim of this study is to evaluate the clinical efficacy of vitamin D (VitD) supplementation in terms of response to treatment and improvement of disease activity in rheumatoid arthritis (RA). Methods: This study analyzed 1180 RA patients' records treated at Mianyang Central Hospital from February 2015 to July 2019. The patients were allocated into VitD group and control group based on their medical regimens. The outcome measures were primary efficacy, defined as treatment response-based EULAR response criteria in RA, and secondary efficacy, defined as improvement in disease activity indicators. Safety was evaluated according to the incidence of all-cause infections. Results: At month 6, the primary efficacy revealed that there were 22.8% good responders and 19.0% moderate responders in the VitD group, and 22.3% good responders and 22.3% moderate responders in the control group; there were no differences between the two groups (p = 0.754). The similar primary efficacy outcomes were observed at months 3, 12, and >12. The secondary efficacy indicated that there were no differences in most indexes between the two groups at months 1, 3, 6, 12, and >12. The subgroups (based on baseline DAS28 (CRP), glucocorticoids use and disease duration) analysis results suggested that VitD group didn't have the advantage for treating RA. The incidence of infections was similar in the two groups. Conclusion: VitD supplementation did not provide additional benefit for anti-rheumatic treatment. These data supported the need for prospective, randomized, controlled trials to evaluate the role of VitD supplementation in treating RA. | |
| 32260259 | Applying Data Mining Techniques for Predicting Prognosis in Patients with Rheumatoid Arthr | 2020 Apr 3 | Rheumatoid arthritis (RA) is a systematic chronic inflammatory disease. The disease mechanism remains unclear and may have resulted from autoimmune problems caused by genetic predisposing and pathogen infection. In clinical practice, selection of the initial treatment is based on the degree of disease activity, and treatment plans will be added gradually according to increased severity of the disease. However, treatment results can be unclear and treatment process uncertain and ambiguous, which can cause healthcare quality to become worse. This study attempts to combine expert opinions to construct various classifiers using a number of data mining techniques to analyze the different prognosis of two patient groups, by predicting whether the inflammatory indicator erythrocyte sedimentation rates of these two groups will be within the normal range with different medication strategies. Clinical data were collected for construction of different classifiers and we evaluate the prediction accuracy rate of each classifier afterwards. The optimum prediction model is selected from these classifiers to predict the prognosis of RA within these treatment strategies and analyze various results. The results show the accuracy rate of the prediction model by Logistic, SVM and DT module were 0.7927, 07829 and 0.9094, respectively. In the RA complications dataset, the accuracy rate of were 0.9393, 0.9290 and 0.9812, respectively. Futhermore, gain ratio was used to further analyze the rules and to discover which branch nodes are the most importance factor. The results of this study are helpful for formulation and development of guidelines for clinical RA treatments, and implementation of a decision support system by using the prediction model can assist medical staff to make correct decisions in the disease's early stage. | |
| 32198574 | Anserine and glucosamine supplementation attenuates the levels of inflammatory markers in | 2020 Mar 20 | Rheumatoid arthritis (RA) is an autoimmune disorder that affects the joint synovium. Anserine is a functional dipeptide containing methylhistidine and β-alanine, and is present in the brain and skeletal muscle of birds and mammals. Glucosamine is an amino sugar used in the synthesis of glycosylated proteins and lipids. We evaluated the effects of anserine and glucosamine on RA. Rats were assigned into the control group, RA group, anserine group (1 mg/kg), glucosamine group (200 mg/kg), or anserine plus glucosamine group (anserine, 1 mg/kg + glucosamine, 200 mg/kg). Treatment was continued for 45 consecutive days and was administered orally. The serum levels of catalase, glutathione peroxidase (Gpx), superoxide dismutase (SOD), reduced glutathione (GSH), lipid peroxidation, uric acid, nitric oxide, ceruloplasmin, zinc, copper, prostaglandin E(2) (PGE(2)), matrix metalloproteinase (MMP)-3, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were assayed. The mRNA and protein levels of nuclear factor (NF)-κB and inducible nitric oxide synthase (iNOS) in synovial tissue were also determined. Anserine plus glucosamine significantly increased the catalase, SOD, Gpx, GSH, and zinc levels compared to the control, anserine, and glucosamine groups. Also, anserine plus glucosamine significantly reduced the PGE(2), MMP-3, TNF-α, IL-1β, and IL-6 levels compared to the control, anserine, and glucosamine groups. Furthermore, anserine plus glucosamine significantly reduced the mRNA and protein levels of NF-κB and iNOS compared to the control, anserine, and glucosamine groups. Therefore, supplementation of anserine plus glucosamine shows therapeutic potential for RA. | |
| 32194408 | Adjunctive Chinese Herbal Products Therapy Reduces the Risk of Ischemic Stroke Among Patie | 2020 | We performed a retrospective cohort study to investigate the association between the risk of ischemic stroke (IS) and the use of Chinese herbal products (CHP) in combination with western medicine (WM) among patients with rheumatoid arthritis (RA). The data were sourced from the registry for beneficiaries, inpatient and ambulatory care claims, and Registry for Catastrophic Illness from the National Health Insurance Research Database (NHIRD) in Taiwan between 1997 and 2011. Patients, who were newly diagnosed with RA between 1997 and 2010, were classified as the CHP group or non-CHP group depending on the presence of absence the adjunctive use of CHP following a diagnosis of RA. A total of 4,148 RA patients were in both the CHP and non-CHP groups after 1:1 matching. Patients in the CHP group had a significantly lower risk of IS compared to patients in the non-CHP group (adjusted hazard ratio [aHR], 0.67; 95% confidence interval [CI], 0.52-0.86). In the CHP group, patients who used CHP for more than 30 days had a lower risk of IS than their counterparts (aHR: 0.61, 95% CI: 0.40-0.91). Gui-Zhi-Shao-Yao-Zhi-Mu-Tang, Shu-Jin-Huo-Xie-Tang, and Du-Huo-Ji-Sheng-Tang might be associated with a lower risk of IS. Finally, the use of CHP in combination with WM was associated with a decreased risk of IS in patients with RA, especially among those who had used CHP for more than 30 days. A further randomized control trial is required to clarify the casual relationship between these results. | |
| 33025881 | Checkpoint inhibition-induced sicca: a type II interferonopathy? | 2020 Jul | The advent of immune checkpoint inhibitor (ICI) therapy for treatment of cancers is unfortunately coupled with a broad panoply of side effects, related to non-specific activation of the immune system. One such side effect is the development of sicca complaints. This culminates in a proportion of patients who, according to the ACR-EULAR 2016 criteria, can be classified as suffering from the autoimmune disease primary Sjögren's syndrome (pSS). Although salivary gland (SG) loss of function is often seen after ICI therapy, the similarities with 'classical' pSS patients would appear to end there. Despite the presence of focal lymphocytic sialadenitis typical for SS in salivary gland biopsies from patients receiving ICI therapy, the nature of the immune infiltration (foci) following ICI use (T-cell dominated) is starkly different to that in pSS (B-cell dominated). The SG parenchyma post-ICI use does not present with germinal centres, lymphoepithelial lesions or IgG plasma cells, which are frequently found in the SG in pSS. Here we review the functional deterioration of SGs following ICI use, the SG parenchyma phenotype associated with this, and ultrasound abnormalities. We conclude by suggesting that ICI-induced SG dysfunction may represent a new interferonopathy, driven by IFNγ, and that this 'pSS' patient cohort may require a different management than classical pSS patients. | |
| 31488308 | AA amyloidosis secondary to adult onset Still's disease: About 19 cases. | 2020 Feb | OBJECTIVE: Adult onset Still's disease (AOSD) is an inflammatory disorder characterized by high spiking fever, evanescent rash, polyarthritis, and many other systemic manifestations. Recurrent or persistent disease can lead to AA amyloidosis (AAA). Our objectives were to present 3 French cases and perform a systematic review of the literature, in order to determine the prevalence, characteristics, predisposing factors, and therapeutic response of AOSD-related AAA. METHODS: A systematic literature review was performed by searching MEDLINE from 1971 to 2018. Two independent investigators selected reports of AAA complicating AOSD. New French cases were identified with the help of the Reference Center for rare Auto-Inflammatory Diseases and Amyloidosis (CEREMAIA). Patients with juvenile idiopathic arthritis were excluded. RESULTS: The prevalence of AAA in AOSD was 0.88% (95%CI [0.49-1.28]) based on 45 articles. In addition to 3 new cases from the CEREMAIA, 16 patients were assessed for clinical presentation, risk factors, and therapeutic response of AOSD-related AAA. Mean age at AOSD onset was 29.6 ± 12.6 years, with a mean delay before AAA diagnosis of 16.75±5.8 years. Renal involvement was the most common manifestation of AAA. The majority of patients presented active AOSD at AAA diagnosis. Various treatments of AOSD-related AAA were attempted including corticosteroids and biotherapies. CONCLUSION: AAA is a rare and severe complication that may occur during the course of uncontrolled active AOSD. It could be prevented by early diagnosis and better control of AOSD, with more frequent use of biotherapies. | |
| 33036832 | Determination of the Voice Parameters in Adult Individuals With Rheumatoid Arthritis and t | 2020 Oct 6 | OBJECTIVES: To assess, through both objective and subjective methods, the complaints of dysphonia among adults with rheumatoid arthritis (RA). The secondary purpose of the study is to determine whether complaints of dysphonia are related to depression and disease activity. STUDY DESIGN: This is a prospective cohort study. METHODS: Eighty subjects (38 RA and 42 healthy volunteers aged 18-65 years old) were included in the study. Participants were evaluated using the Voice Handicap Index-10 (VHI-10) to assess voice complaints. Laryngeal findings of participants with RA were performed by videolaryngoscopy. Maximum phonation time (MPT) measurements and acoustic voice analysis (PRAAT software) were performed to evaluate the presence of objective dysphonia. Disease activity of individuals was calculated by using Disease Activity Score-28 (DAS-28) scale. Beck Depression Inventory (BDI) was applied to evaluate the symptoms of depression in participants. RESULTS: The prevalence of laryngeal symptoms of participants with RA was %42.1. According to the cut-off score of VHI-10, 15.8% of the participants in the study group had voice complaints. Comparing the MPT and acoustic voice analyses values of the study and control group, the MPT of the RA participants were statistically lower (P< 0.05). Perturbation parameters of male participants in the study and control groups were statistically different. 15.8% of participants in RA group had symptoms of depression. However, there was no statistically significant difference between BDI and acoustic voice parameters. CONCLUSIONS: RA may be associated with voice disorders. Male patients with RA had worse jitter parameters, but the number of participants was low. Dysphonia may not be associated with depression and disease activity in RA patients. | |
| 32742333 | Serum COX-2 and FOXO3a in patients with rheumatoid arthritis and correlation with disease | 2020 Aug | Expression levels of serum cyclooxygenase (COX)-2 and forkhead box O3a (FOXO3a) in patients with rheumatoid arthritis (RA) and the correlation with disease activity were investigated. Sixty patients with RA admitted to the People's Hospital of Guangxi Zhuang Autonomous Region (study group; 28 active patients and 32 remissive patients), and further 30 healthy subjects undergoing physical examinations during the same period (control group) were enrolled in this study. RT-qPCR and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression levels of COX-2 and FOXO3a in serum. According to DAS28 score, the patients were divided into active and remissive patients, between whom the expression levels were compared. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic values of COX-2 and FOXO3a for disease activity. Pearson's correlation coefficient was used to analyze the correlation of the two markers with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and DAS28 score. The expression levels of COX-2 and FOXO3a in active and remissive patients were significantly higher than those in the control group (both P<0.05), and those in active patients were significantly higher than those in remissive patients (both P<0.05). The areas under the ROC curves (AUCs) of COX-2 and FOXO3a were 0.748 and 0.802, respectively, suggesting that the two markers have high diagnostic value. The expression levels of COX-2 and FOXO3a were positively correlated with ESR, CRP, and DAS28 score of active and remissive patients (both P<0.05). In conclusion, the expression levels of COX-2 and FOXO3a in patients with RA are upregulated, thus, the two markers may be involved in the development and progression of the disease. The expression levels of COX-2 and FOXO3a are related to the disease activity of RA, and therefore can be used as diagnostic indicators for the disease activity. | |
| 32685594 | A Network Meta-Analysis to Compare Effectiveness of Baricitinib and Other Treatments in Rh | 2020 | BACKGROUND/OBJECTIVES: This article compares the effectiveness of baricitinib (BARI) 4 mg (oral, Janus kinase [JAK] 1/2 inhibitor) versus other targeted synthetic/biologic disease-modifying antirheumatic drugs, in combination with methotrexate (MTX), in moderate-to-severe rheumatoid arthritis patients with inadequate response (IR) to MTX. METHODS: A systematic literature review was conducted to identify randomized controlled trials (RCTs) of the interventions of interest. Bayesian network meta-analyses (NMA) were used to compare American College of Rheumatology (ACR) responses at 24 weeks. A series of prespecified sensitivity analyses addressed the potential impact of, among others, baseline risk, treatment effect modifiers, and trial design on treatment response. RESULTS: Nineteen RCTs were included in the NMA (primary analysis). For ACR20, BARI 4 mg + MTX was found to be more effective than adalimumab (ADA) 40 mg + MTX (Odds Ratio [OR] 1.33), abatacept (ABA) 10 mg + MTX (IV/4 weeks) (OR 1.45), infliximab (IFX) 3 mg + MTX (IV/8 wks) (OR 1.63), and rituximab (RTX) 1000 mg + MTX (OR 1.63). No differences were found on ACR50. For ACR70, BARI 4 mg + MTX was more effective than ADA 40 mg + MTX (OR 1.37), ABA 10 mg + MTX (OR 1.86), and RTX 1000 mg + MTX (OR 2.26). Sensitivity analysis including 10 additional RCTs with up to 20% of patients with prior biologic use showed BARI 4 mg + MTX to be more effective than tocilizumab (TCZ) 8 mg + MTX on ACR20 (OR 1.44). Results for all sensitivity analyses were consistent with the direction and magnitude of the primary results. Key limitations include the time span in which trials were conducted (1999-2017), during which patient characteristics and treatment approaches might have changed. CONCLUSION: This NMA suggests that BARI 4 mg + MTX is an efficacious treatment option in the MTX-IR population as evidenced by the robustness of results. | |
| 32355550 | Role of RP11-83J16.1, a novel long non-coding RNA, in rheumatoid arthritis. | 2020 | This study aimed to explore the effects of long non-coding RNA (lncRNA) expression on rheumatoid arthritis (RA). LncRNA expression profiles were obtained from the synovial tissues of five RA patients and five age-/gender-matched controls by RNA-Seq. Six candidate lncRNAs were then chosen and their levels in synovial fluid further examined in 25 RA patients and 25 health controls using RT-qPCR. The effects of lncRNA RP11-83J16.1 overexpression and knockdown on RA fibroblast-like synoviocytes (RA-FLS) function, inflammation state, and URI1, FRAT1, and β-catenin levels were assessed. After RNA-Seq, lncRNA expression profiles clearly distinguished RA patients from controls, and 190 upregulated lncRNAs and 131 downregulated lncRNAs were identified, which were mainly enriched in proliferative/immune/inflammatory pathways. Results of RT-qPCR showed that the levels of lncRNAs MTCO2P12, KCNQ5-IT1 and RP11-83J16.1 were increased, whereas lncRNAs LINC00570, RP11-342M1.6, and REXO1L4P were decreased in RA patients compared to controls. Notably, lncRNA RP11-83J16.1 correlated with increased inflammation and disease activity in RA patients. Additionally, lncRNA RP11-83J16.1 promoted cell proliferation, migration, invasion and inflammation, reduced apoptosis, and positively regulates cellular URI1, FRAT1 and β-catenin expression in RA-FLS. Rescue experiments revealed that URI1 overexpression compensated for the regulatory effects of lncRNA RP11-83J16.1 knockdown in RA-FLS. In conclusion, lncRNA RP11-83J16.1, a novel lncRNA identified by RNA-Seq, correlates with increased risk and disease activity of RA, and promotes RA-FLS proliferation, migration, invasion and inflammation by regulating URI1 and downstream β-catenin pathway components. | |
| 34138288 | ROS-Responsive Berberine Polymeric Micelles Effectively Suppressed the Inflammation of Rhe | 2020 Mar 20 | Rheumatoid arthritis (RA) is an autoimmune disease, which attacks human joint system and causes lifelong inflammatory condition. To date, no cure is available for RA and even the ratio of achieving remission is very low. Hence, to enhance the efficacy of RA treatment, it is essential to develop novel approaches specifically targeting pathological tissues. In this study, we discovered that RA synovial fibroblasts exhibited higher reactive oxygen species (ROS) and mitochondrial superoxide level, which were adopted to develop ROS-responsive nano-medicines in inflammatory microenvironment for enhanced RA treatment. A selenocystamine-based polymer was synthesized as a ROS-responsive carrier nanoplatform, and berberine serves as a tool drug. By assembling, ROS-responsive berberine polymeric micelles were fabricated, which remarkably increased the uptake of berberine in RA fibroblast and improved in vitro and in vivo efficacy ten times higher. Mechanistically, the anti-RA effect of micelles was blocked by the co-treatment of AMPK inhibitor or palmitic acid, indicating that the mechanism of micelles was carried out through targeting mitochondrial, suppressing lipogenesis and finally inhibiting cellular proliferation. Taken together, our ROS-responsive nano-medicines represent an effective way of preferentially releasing prodrug at the inflammatory microenvironment and improving RA therapeutic efficacy. | |
| 32548059 | Polymorphisms of Pre-miR-499 rs3746444 T/C and Pre-miR-146a rs2910164 C/G in the Autoimmun | 2020 Apr | BACKGROUND: The present research is a case-control study to analyze the influence of pre-miRNA-146a rs2910164 and pre-miRNA-499 rs3746444 polymorphisms as candidate susceptibility factors for both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: Polymorphism in miR146 and miR499 using ARMS-PCR was genotyped on 139 autoimmune disease (AD) patients (89 RA and 50 SLE) referred to Educational Hospitals of Khorramabad, Lorestan Province, west of Iran in 2018-2019 and 237 healthy control subjects. RESULTS: A significant increase in the likelihood of carrying the GC vs. GG of pre-miR146-rs2910164 and T vs C allele of pre-miR499- rs3746444 in patients with RA was found. On the contrary, patients with RA were less likely to carry the TC + CC vs TT genotype and the C vs T allele of pre-miR499- rs374644. In females with the GC vs GG and GC+ CC vs GG genotypes, a significant association was found with the increased risk of RA. Interestingly, the genotypic combination of TC of the pre-miR499-rs374644 with GG of pre-miR146-rs2910164 more strongly decreased the risk of RA. In patients with SLE, no notable associations were found between both pre-miRNA-146a rs2910164 and pre-miRNA-499 rs3746444 with risk of disease. CONCLUSION: Genetic polymorphisms of miR146 rs2910164 is associated with RA susceptibility especially in females. Interestingly, there is a potential in miR499 to reduce the risk with the protective effect of gene-gene interactions on miR146 in RA disease. | |
| 32025586 | Design of an anti-inflammatory diet (ITIS diet) for patients with rheumatoid arthritis. | 2020 Mar | BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects synovial joints, leading to inflammation, joint destruction, loss of function, and disability. Although recent pharmaceutical advances have improved treatment of RA, patients with RA often inquire about dietary interventions to improve RA symptoms, as they perceive rapid changes in their symptoms after consumption of certain foods. There is evidence that some ingredients have pro- or anti-inflammatory effects. In addition, recent literature has shown a link between diet and microbiome changes. Both diet and the gut microbiome are linked to circulating metabolites that may modulate inflammation. However, evidence of the effects of an anti-inflammatory and probiotic-rich diet in patients with RA is scarce. There is also a need for biological data to support its anti-inflammatory effects. METHODS: The main goal of this study is to delineate the design process for a diet tailored to our RA population. To achieve this goal, we collected information on diet, supplements, cooking methods, and intake of different ingredients for each patient. Different groups were interviewed, and their feedback was assessed to design a diet that incorporates suggested anti-inflammatory ingredients in a manner that was easy for patients to adopt based on their lifestyles and backgrounds. RESULTS: We designed a diet that includes a high intake of potential anti-inflammatory ingredients. Feedback from highly motivated patients was critical in constructing an anti-inflammatory diet (ITIS diet) with elevated adherence. CONCLUSION: In order to tailor our diet, we surveyed our patients on several different parameters. We obtained important feedback on how feasible our ITIS diet is for RA patients. Using this feedback, we made minor improvements and finalized the design of the ITIS diet. This diet is being used in an on-going pilot study to determine their anti-inflammatory effect in pain and joint swelling in RA patients. TRIAL REGISTRATION: Not applicable. | |
| 33240258 | Circulating Neutrophil Extracellular Traps Signature for Identifying Organ Involvement and | 2020 | Adult-onset Still's disease (AOSD) is an autoinflammatory disease with multisystem involvement. Early identification of patients with severe complications and those refractory to glucocorticoid is crucial to improve therapeutic strategy in AOSD. Exaggerated neutrophil activation and enhanced formation of neutrophil extracellular traps (NETs) in patients with AOSD were found to be closely associated with etiopathogenesis. In this study, we aim to investigate, to our knowledge for the first time, the clinical value of circulating NETs by machine learning to distinguish AOSD patients with organ involvement and refractory to glucocorticoid. Plasma samples were used to measure cell-free DNA, NE-DNA, MPO-DNA, and citH3-DNA complexes from training and validation sets. The training set included 40 AOSD patients and 24 healthy controls (HCs), and the validation set included 26 AOSD patients and 16 HCs. Support vector machines (SVM) were used for modeling and validation of circulating NETs signature for the diagnosis of AOSD and identifying patients refractory to low-dose glucocorticoid treatment. The training set was used to build a model, and the validation set was used to test the predictive capacity of the model. A total of four circulating NETs showed similar trends in different individuals and could distinguish patients with AOSD from HCs by SVM (AUC value: 0.88). Circulating NETs in plasma were closely correlated with systemic score, laboratory tests, and cytokines. Moreover, circulating NETs had the potential to distinguish patients with liver and cardiopulmonary system involvement. Furthermore, the AUC value of combined NETs to identify patients who were refractory to low-dose glucocorticoid was 0.917. In conclusion, circulating NETs signature provide added clinical value in monitoring AOSD patients. It may provide evidence to predict who is prone to be refractory to low-dose glucocorticoid and help to make efficient therapeutic strategy. | |
| 32471733 | Differences in clinical features between small fiber and sensitive large fiber neuropathie | 2020 Sep | BACKGROUND: To distinguish large (LFN) and small fiber neuropathies (SFN) in Sjögren's syndrome (SS) requires electroneuromyography (EMG) first, but this is time-consuming and has sometimes a limited accessibility, which can lead to a diagnostic delay. We aimed to identify clinical features that could distinguish SFN from sensitive LFN in SS. METHODS: The study included patients with SS who were monitored in the internal medicine and neurology departments at Angers University Hospital between 2010 and 2016, and who were tested for suspected peripheral neuropathy. Patients with clinical motor involvement were excluded. LFN diagnosis was based on EMG. SFN diagnosis was based on intraepidermal nerve fiber density on skin biopsies in patients with no abnormality on EMG. RESULTS: LFN and SFN were diagnosed respectively in 22 (6.9%) and 17 (5.4%) patients among 317 patients with SS. Prevalence of anti-SSA antibodies was lower in the SFN group compared to the LFN group (p=0.002). The types of paresthesia did not differ between the 2 groups. After adjustment for age and sex, SFN was associated with dysautonomia (p=0.01, OR 8.4 [CI 95%: 1.7-42.4]) and without length-dependent topography (p=0.03, OR 0.2 [0.04-0.8] in comparison with the LFN group. CONCLUSIONS: An association of non-length-dependent pattern and dysautonomia seems to predict the absence of LFN in SS and encourages the search for SFN. In contrary, patients with length-dependent involvement and without dysautonomia should be prioritized for EMG. | |
| 32221700 | Early onset primary Sjögren syndrome, clinical and laboratory characteristics. | 2020 Sep | INTRODUCTION/OBJECTIVES: Primary Sjögren syndrome (pSS) is usually encountered between the fourth and sixth decades. It is known that the age of onset in autoimmune diseases may affect the clinical features. In this study, we aimed to investigate the clinical and laboratory characteristics of early onset pSS patients. METHOD: The data of 352 pSS patients were analyzed retrospectively. The patients were divided into two groups as those with the onset age of 35 or younger (early-onset) and those with the onset age of older than 35. The clinical, laboratory, and serological characteristics of the two groups were compared. p < 0.05 was considered statistically significant. RESULTS: Forty patients in the group with an onset age of 35 or younger (11.4%) and 312 patients with an onset age of older than 35 (88.6%) were analyzed. The frequency of skin (22.5% vs 1.9%, p < 0.001) and renal involvement (10% vs 2.2%, p = 0.026) was significantly higher in the early-onset group than the late-onset group. There was no significant difference between the two groups in terms of xerostomia, eye dryness, arthritis, and other systemic involvement. Anti-Ro52 positivity (p = 0.04), elevated serum IgG levels (p = 0.004), and low C4 (p = 0.002) presence were more frequent in the early-onset group. CONCLUSIONS: Consequently, it is seen that the clinical phenotype of early-onset pSS patients may be different to those with later onset. Especially the more frequent observation of poor prognostic factors at early-onset ages shows the necessity to monitor these patients more regularly. KEY POINTS: • The clinical and laboratory features of patients with early-onset primary Sjogren syndrome may differ from late-onset patients. |