Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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33953620 | Improvement of HbA1c in Patients with Type 2 Diabetes Mellitus and Rheumatoid Arthritis Tr | 2021 | OBJECTIVE: The aim of our study was to evaluate the possible role of biological treatments for rheumatoid arthritis (RA) in improving the glycemic profile in patients affected not only by RA but also by type 2 diabetes mellitus (2TDM). METHODS: An observational retrospective study was conducted using data from patients referred to our Rheumatology Unit. Patients with active RA despite standard DMARDs therapy and concomitant 2TDM were selected into one of five exposure groups to first-line bDMARDs (adalimumab, golimumab, etanercept, tocilizumab, sarilumab) and observed for the outcome of CRP, ESR, DAS28CRP and glycated hemoglobin (HbA1c) variations. RESULTS: After the start of treatment, there was a significant reduction in the values of acute phase reactants ESR and CRP (p<0.01), DAS28-CRP (p<0.01) and HbA1C (p<0.05), in the absence of any confounding factors such as a reduction in BMI or a change in steroid doses. There was no statistically significant difference between the various treatments. Anti-IL6 drugs appear to be associated with a slightly greater reduction in HbA1c values, bordering on statistical significance (p=0.047). CONCLUSION: Initiation of a bDMARD appears to be associated with an improvement in concomitant 2TDM in patients with active RA, which, in the first hypothesis, is linked with a reduction of the inflammatory milieu. | |
33776780 | Dysregulation of lncRNAs in Rheumatoid Arthritis: Biomarkers, Pathogenesis and Potential T | 2021 | Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology, mainly manifested by persistent abnormal proliferation of fibroblast-like synoviocytes (FLSs), inflammation, synovial hyperplasia and cartilage erosion, accompanied by joint swelling and joint destruction. Abnormal expression or function of long noncoding RNAs (lncRNAs) are closely related to human diseases, including cancers, mental diseases, autoimmune diseases and others. The abnormal sequence and spatial structure of lncRNAs, the disorder expression and the abnormal interaction with the binding protein will lead to the change of gene expression in the way of epigenetic modification. Increasing evidence demonstrated that lncRNAs were involved in the activation of FLSs, which played a key role in the pathogenesis of RA. In this review, the research progress of lncRNAs in the pathogenesis of RA was systematically summarized, including the role of lncRNAs in the diagnosis of RA, the regulatory mechanism of lncRNAs in the pathogenesis of RA, and the intervention role of lncRNAs in the treatment of RA. Furthermore, the activated signal pathways, the role of DNA methylation and other mechanism have also been overview in this review. | |
33451719 | The use of digital tomosynthesis in rheumatology: a systematic review of the literature fo | 2021 Mar | BACKGROUND AND AIMS: Digital tomosynthesis has proven useful in the evaluation of damage to joints. This study aims to describe the most common digital tomosynthesis findings for four rheumatological entities and to compare the usefulness of this technique with that of other imaging techniques. MATERIALS AND METHODS: Following the PRISMA guidelines, we systematically searched the literature for articles about the use of digital tomosynthesis in rheumatoid arthritis, osteoarthritis, spondyloarthritis, and gout. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) criteria to evaluate the quality of the articles included. RESULTS: We included 13 articles. For rheumatoid arthritis, osteoarthritis, and spondyloarthritis, digital tomosynthesis detected bone abnormalities better than plain-film X-rays; however, for gout, the results were variable. CONCLUSIONS: Digital tomosynthesis can play an important role in the evaluation of skeletal abnormalities in rheumatological disease, especially compared to plain-film X-rays. | |
34751783 | Impact of Concomitant Chronic Kidney Disease on Hospitalized Infections and Remission in P | 2021 Nov 9 | OBJECTIVE: To investigate the impact of concomitant chronic kidney disease (CKD) on unfavourable clinical events and remission in Japanese patients with rheumatoid arthritis (RA). METHODS: We included 5,103 patients with RA with CKD from the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort in 2012. CKD stages were classified into four groups: CKD with normal eGFR ≥60 ml/min/1.73 m2 and proteinuria; mild CKD, eGFR ≥45-<60; moderate CKD, eGFR ≥30-<45; and severe CKD, eGFR <30. We assessed the association between concomitant CKD and the occurrence of unfavourable clinical events or achieving remission during a 5-year observational period. RESULTS: Of the 5,103 patients with RA, 686 (86.6%) had CKD. Concomitant CKD was associated with hospitalized infections (adjusted hazard ratio [aHR] 1.52, 95% confidence interval [CI] 1.07-2.13, p=0.02), especially in the moderate to severe CKD group (aHR 1.93, 95% CI 1.12-3.13, p=0.02). Of all subjects, 2,407 (47.2%) had active RA at baseline and 401 (16.7%) had CKD. Concomitant CKD was also associated with failure of achieving remission (aHR 0.82, 95% CI 0.68-0.99, p=0.04). CONCLUSION: Concomitant CKD was a risk factor for hospitalized infections in Japanese patients with RA and failure of achieving remission in patients with active RA. | |
34095413 | Disease-associated reference intervals for twenty laboratory tests in patients with rheuma | 2021 May | BACKGROUND: Population based reference intervals are fundamental for interpreting results for quantitative laboratory tests. In patients with a specific chronic disorder, however, results of various tests may regularly be different than in healthy individuals. Health-associated reference intervals may therefore have limited value in such patients. Instead, disease-associated reference intervals may be useful, as they describe the results distribution in populations resembling the specific patients. Few disease-associated reference intervals are available in the literature. The aim of this study was to estimate reference intervals for common laboratory tests for patient populations with rheumatoid arthritis, Crohn's disease or ulcerative colitis without significant comorbidity, using a novel algorithm. MATERIAL AND METHODS: Laboratory test results and hospital discharge diagnoses were collected for relevant patients. An algorithm was developed to identify discharge diagnoses significantly associated with high or low results for specific tests. After excluding patients with such diagnoses, reference intervals were estimated, representing results distributions in patients with each of the specific chronic disorders, but without significant comorbidity. RESULTS: Disease-associated reference intervals were estimated for 20 common laboratory tests. Most of the estimated reference limits were significantly different from corresponding health-associated reference limits. Thirty percent of the estimated reference intervals were different from estimates based on crude patient populations, indicating that the algorithm applied managed to exclude patients with relevant comorbidity. CONCLUSION: Disease-associated reference intervals could be estimated for a number of tests in patients with rheumatoid arthritis, ulcerative colitis or Crohn's disease using a highly automated algorithm based on routinely recorded patient data. | |
34046564 | Change of ARASHI scores for large joints in rheumatoid arthritis patients treated with aba | 2021 Mar | OBJECTIVES: This study aims to investigate large joint damage progression using the assessment of rheumatoid arthritis by scoring of large joint destruction and healing in radiographic imaging (ARASHI) score in patients with rheumatoid arthritis (RA) treated with abatacept for three years. PATIENTS AND METHODS: A total of 71 consecutive patients with RA (7 males, 64 females; median age 68 years; range, 41 to 81 years) and joint lesions (141 shoulders, 139 elbows, 141 hips, 134 knees, and 142 ankles) treated with abatacept for three years were examined. Radiographic changes were assessed using the ARASHI score, and factors associated with radiographic progressive damage of large joints were analyzed using multivariate logistic regression. RESULTS: The three-year radiographic progressive damage rates for the upper and lower limb large joints were 18.3% and 22.5%, respectively. Rates for the shoulder and knee decreased significantly (p=0.025 and 0.039, respectively), whereas rate for the ankle increased significantly (p=0.043). Multivariate logistic regression analysis identified the baseline ARASHI status score as an independent predictor of progressive damage of upper limb large joints within three years (p=0.004; odds ratio, 1.17). The cutoff value of the ARASHI status score for the upper limb large joints was 4, as determined from the receiver operating characteristics curve. No significant predictors of progressive damage were identified in the lower limb large joints within three years. CONCLUSION: The greatest suppression of the radiographic progressive damage of large joints was achieved for the shoulders and knees. Meanwhile, ankle damage progressed. Therefore, ankle joint damage should be monitored even in patients treated with abatacept. In the upper limbs, prescribing abatacept to patients with RA depending on their state of upper limb large joint damage may suppress damage progression. | |
33976462 | Selected psychological factors and medication adherence in patients with rheumatoid arthri | 2021 | OBJECTIVES: The aim of the study was to determine the relationship between medication adherence (MA) and selected psychological factors in a group of patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: The cross-sectional study was conducted in four rheumatology outpatient clinics in Silesia, Poland. The tests used were the Medication Adherence Questionnaire (MAQ), the Multidimensional Health Locus of Control Scale (MHLC), the Coping Inventory for Stressful Situations (CISS), and the Mindful Attention Awareness Scale (MAAS). The analysis involved 106 adult patients diagnosed with RA at least 6 months before, who were prescribed medication, with disease at any stage and with stable comorbidities. Software was used to perform analyses of frequency, basic descriptive statistics, including the Kolmogorov-Smirnov test, Student's t-test for independent samples, intergroup univariate variance, Pearson's r correlation coefficient, Spearman's rank correlation Ï coefficient, Fisher's exact test and stepwise linear regression. RESULTS: Powerful Others Health Locus of Control (PHLC), Internal Health Locus of Control (IHLC) and age of the subjects, F(3, 102) = 8.05; p < 0.001 explained 16.8% of the variation in the adherence level for the entire group. In the group of women PHLC and IHLC, F(2, 80) = 10.04; p < 0.001 were included in the model, which explained 18.1% of variation in MA. PHLC was the most significant factor in the group of women (β = 0.55; p < 0.001) and in the entire group (β = 0.48; p < 0.001). In the group of men, Social Diversion Style (SDS), F(1, 21) = 5.81; p = 0.02 was included in the model, which explained 17.9% of the variation in the MA level. CONCLUSIONS: The study identified some psychological predictors of adherence, which explained 16.8% of the variability. Factors increasing the likelihood of medication adherence in patients with rheumatoid arthritis include a strong belief in the power of others, low level of internal health locus of control, and advanced age. | |
34540433 | Non-Articular Felty Syndrome Refractory to Granulocyte Colony-Stimulating Factor Therapy. | 2021 Aug | Felty syndrome (FS), an uncommon manifestation seen in patients with rheumatoid arthritis (RA), usually presents as a triad of erosive arthritis, splenomegaly, and neutropenia. It is extremely rare for RA to present as FS or develop after initially presenting as neutropenia and splenomegaly. In this report, we describe a case of a 55-year-old woman who initially presented with fever and vaginal pain. Her sepsis workup revealed genital herpes in the setting of leukopenia, with an incidental finding of splenomegaly on imaging. The patient was managed with filgrastim and valacyclovir. Two weeks later, she presented again with pleuritic chest pain and worsening leukopenia. This led to an extensive workup by the hematology team to diagnose and confirm the diagnosis of FS. We also engage in a review of the existing literature of such cases and emphasize the importance of serological testing for RA in patients with leukopenia and splenomegaly, even in the absence of joint symptoms or prior diagnosis of RA. The management should be guided towards treating the infection, correcting the neutropenia, and treating the underlying chronic disease. | |
34918127 | Differences in patients' population and efficacy/effectiveness of biologic disease-modifyi | 2021 Sep 10 | OBJECTIVES: To evaluate the differences in patients' population and efficacy/effectiveness of biological disease-modifying antirheumatic drugs (bDMARDs) between randomized controlled trials (RCTs) and clinical practice in patients with rheumatoid arthritis. METHODS: We reviewed inclusion criteria in Phase II or III RCTs of bDMARDs conducted in Japan. The Institute of Rheumatology, Rheumatoid Arthritis study participants during the period when each RCT was conducted (Cohort A) and new bDMARD users at our institute in 2016 (Cohort B) were assessed for the fulfilment of the inclusion criteria. The effectiveness of bDMARDs in our cohort and their efficacy in RCTs were compared using the inverse-variance method. RESULTS: Nineteen RCTs were selected. The mean proportions of patients fulfilling all inclusion criteria of each RCT in Cohorts A and B were 2.3% and 7.6%, respectively. The pooled proportion ratios (95% confidence interval) for achieving the American College of Rheumatology 20 (ACR20), ACR50, ACR70, and disease activity score 28 remission in non-eligible cases for eight RCTs versus all corresponding RCTs were 0.38 (0.30-0.51), 0.41 (0.30-0.57), 0.54 (0.35-0.82), and 1.28 (1.10-1.56), respectively. CONCLUSIONS: Few rheumatoid arthritis patients fulfilled the inclusion criteria of the RCTs in clinical settings. There was a difference in the efficacy/effectiveness of bDMARDs between RCTs and clinical practice. | |
33654690 | Sudden Hearing Loss and Multiple Cranial Nerve Palsies in Autoimmune disease: A Case Repor | 2021 Jan | INTRODUCTION: The relationship between autoimmune disease and sensorineural loss is well documented in literature. Immune mediated sudden hearing loss is asymmetric, bilateral and rapidly progressive but responds well to steroid therapy. However association of cranial nerve neuropathies with sudden hearing loss is rare. CASE REPORT: A 41 year old female presented with sudden mixed hearing loss and developed multiple cranial nerve palsies within a month. Blood and Cerebrospinal fluid analysis revealed an undiagnosed rheumatoid arthritis. She responded well to definitive therapy with cyclophosphamide and azathioprine. CONCLUSION: If sudden hearing loss is associated with cranial neuropathy, an autoimmune work-up is highly recommended. | |
34743757 | Decentralizing healthcare in Norway to improve patient-centered outpatient clinic manageme | 2021 Nov 8 | A growing population of older adults and improved effective treatments for inflammatory rheumatic diseases will increase the demand for more healthcare resources that already struggle with staggering outpatient clinic waiting times. Transformative delivery care models that provide sustainable healthcare services are urgently needed to meet these challenges. In this mini-review article, a proposed Lifelong Treatment Model for a decentralized follow-up of outpatient clinic patients living with rheumatoid arthritis is presented and discussed.Our conceptual model follows four steps for a transformative care delivery model supported by an Integrated Practice Unit; (1) Diagnosis, (2) Treatment, (3) Patient Empowered Disease Management, and (4) Telehealth. Through an Integrated Practice Unit, a multidisciplinary team could collaborate with patients with rheumatoid arthritis to facilitate high-value care that addresses most important outcomes of the patients; (1) Early Remission, (2) Decentralization, (3) Improved Quality of Life, and (4) Lifelong Sustain Remission.The article also addresses the growing challenges for the healthcare delivery system today for patients with rheumatoid arthritis and proposes how to reduce outpatient clinic visits without compromising quality and safety. | |
34692791 | PCSK9/LDLR System and Rheumatoid Arthritis-Related Atherosclerosis. | 2021 | Background/Aims: Rheumatoid arthritis (RA) is associated with the emergence of cardiovascular disease, while chronic inflammation is considered a common denominator for their parallel progression. The Proprotein convertase subtilisin/kexin type 9 (PCSK9)/LDL-Receptor (LDLR) system is of high importance during atherogenesis, via regulating the clearance of LDL from the circulation; nevertheless the role of this molecular mechanism during RA-related atheromatosis is not known. Methods: Herein, high-resolution ultrasound measurements for arterial hypertrophy, atheromatosis and arterial stiffness as well as comprehensive biochemical profiling were performed in 85 RA patients. The circulating levels of PCSK9 and LDLR were measured and their potential associations as well as of the PCSK9/LDLR ratio with patients' characteristics and the degree of atherosclerosis were investigated. Results: Increased LDLR levels and decreased PCSK9/LDLR ratio were found in RA patients with at least 2 atheromatic plaques as compared to the ones without any plaques. In addition the levels of both PCSK9 and LDLR were positively correlated with the presence of atheromatic plaques as an age- and gender- adjusted multivariate analysis revealed. Conclusions: Our data imply that the PCSK9/LDLR system plays a significant role during RA-related atherosclerosis and may therefore be used as a screening tool for disease progression in the future. | |
34522877 | Causal risk and protective factors in rheumatoid arthritis: A genetic update. | 2021 | The characterization of risk and protective factors in complex diseases such as rheumatoid arthritis (RA) has evolved from epidemiological studies, which test association, to the use of Mendelian randomization approaches, which test direct relationships. Indeed, direct associations with the mucosal origin of RA are retrieved with periodontal disease (Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans predominantly), interstitial lung involvement, tobacco smoking and air pollutants. Next, factors directly associated with an acquired immune response include genetic factors (HLA DRB1, PTPN22), capacity to produce anti-modified protein antibodies (AMPA), and relatives with a history of autoimmune diseases. Finally, factors can be also classified according to their direct capacity to interfere with the IL-6/CRP/sIL-IL6R proinflammatory pathway as risk factor (body fat, cardiometabolic factors, type 2 diabetes, depressive syndrome) or either as protective factors by controlling of sIL-6R levels (higher education level, and intelligence). Although some co-founders have been characterized (e.g. vitamin D, physical activity, cancer) the direct association with sex-discrepancy, pregnancy, and infections among other factors remains to be better explored. | |
34443836 | Biogenic Selenium Nanoparticles: Potential Solution to Oxidative Stress Mediated Inflammat | 2021 Aug 5 | Rheumatoid arthritis (RA) is a common chronic inflammation-mediated disorder having systematic complications. RA triggers a self-directed inflammatory and immunological cascade that culminates in joint destruction. Though a range of treatment options are available, none of them are without adverse effects and this has led researchers to search for alternative solutions. Nanomedicine has emerged as a powerful therapeutic alternative, and selenium (Se) is an essential micronutrient trace element that has a crucial role in human health and disease. Selenium nanoparticles (SeNPs) derived from biological sources, such as plants, bacteria, fungi, and proteins, have exhibited remarkable candidate properties and toxicological profiles, and hence have shown potential to be used as antirheumatic agents. The potential of SeNPs can be attributed to the effect of functional groups bound to them, concentration, and most importantly to their nano range size. The antirheumatic effect of SeNPs is considerable due to its potential in amelioration of oxidative stress-mediated inflammation via downregulation of radical and nonradical species, markers of inflammation, and upregulation of inherent antioxidant defenses. The size and concentration impact of SeNPs has been shown in the subsequent antioxidant and anti-inflammatory properties. Moreover, the article emphasizes the role of these biogenic SeNPs as a notable option in the nanomedicine arena that needs to be further studied as a prospective remedial alternative to cure RA and medication-related adverse events. | |
34335264 | Nanomaterials Manipulate Macrophages for Rheumatoid Arthritis Treatment. | 2021 | Rheumatoid arthritis (RA) is a chronic, progressive, and systemic inflammatory autoimmune disease, characterized by synovial inflammation, synovial lining hyperplasia and inflammatory cell infiltration, autoantibody production, and cartilage/bone destruction. Macrophages are crucial effector cells in the pathological process of RA, which can interact with T, B, and fibroblast-like synovial cells to produce large amounts of cytokines, chemokines, digestive enzymes, prostaglandins, and reactive oxygen species to accelerate bone destruction. Therefore, the use of nanomaterials to target macrophages has far-reaching therapeutic implications for RA. A number of limitations exist in the current clinical therapy for patients with RA, including severe side effects and poor selectivity, as well as the need for frequent administration of therapeutic agents and high doses of medication. These challenges have encouraged the development of targeting drug delivery systems and their application in the treatment of RA. Recently, obvious therapeutic effects on RA were observed following the use of various types of nanomaterials to manipulate macrophages through intravenous injection (active or passive targeting), oral administration, percutaneous absorption, intraperitoneal injection, and intra-articular injection, which offers several advantages, such as high-precision targeting of the macrophages and synovial tissue of the joint. In this review, the mechanisms involved in the manipulation of macrophages by nanomaterials are analyzed, and the prospect of clinical application is also discussed. The objective of this article was to provide a reference for the ongoing research concerning the treatment of RA based on the targeting of macrophages. | |
34257966 | Are antibodies to fine specificities of citrullinated peptides/proteins useful for stratif | 2021 | BACKGROUND: In rheumatoid arthritis (RA), antibodies to citrullinated protein (ACPA) are believed to be heterogeneous and patient stratification by antibody profiling raised clinical interest for patient management. However, heterogeneity might be partially artificial because of the use of heterogeneous methods for ACPA detection. In recent work instead, we found that ACPA were mainly directed towards a single fibrin-derived peptide, β60-74BiotNt, but a comparative analysis with the presence of other ACPA specificities is still lacking. OBJECTIVES: To present an overview of RA patients' stratification based on the detection of the main ACPA fine specificities with the same method as compared to that of anti-β60-74BiotNt antibodies. METHODS: Over 4500 measurements were performed with more than 22 standardised ELISAs, sera from 180 RA patients and 200 to 436 non-RA rheumatic disease controls. RESULTS: Four to 81% of RA patients had ACPA towards various targets, confirming the heterogeneity of ACPA specificities. However, the subgroups of patients overlapped up to 97% with ACPA levels of correlation coefficients up to 0.8, showing redundancy of some targets. Multiplexing decreased diagnostic specificity from 95% to 64%. Instead, anti-β60-74BiotNt detection identified almost all ACPA-positive patients. CONCLUSIONS: Antibodies to citrullinated protein multiplexing shows some degree of redundancy and is not suitable for diagnostic purposes. ACPA fine specificities might be less heterogeneous than perceived by sera testing on multiple peptides. Patient stratification largely depends on detection methods and requires standardisation. | |
33897281 | E2F2 stimulates CCR4 expression and activates synovial fibroblast-like cells in rheumatoid | 2021 | AIM OF THE STUDY: E2F transcription factor 2 (E2F2) has increased expression in synovial tissues of rheumatoid arthritis (RA) and stimulates interleukin (IL)-1 α and IL-β production in cultured RA synovial fibroblast-like cells (RASF), which supports the importance of E2F2 in RA pathogenesis. This study investigated the effect and mechanism of E2F2 in RA. MATERIAL AND METHODS: Cultured RASF were transfected with anti-E2F2 siRNA, and the expression profile was analyzed with an inflammatory response and autoimmunity PCR array loaded with 84-relative genes to explore the pathogenic pathway of E2F2. Apoptosis, migration and tube-like structure formation in the RASF with transfection of anti-E2F2 siRNA or E2F2-expressing plasmids were examined using flow cytometry, transwell assays and Matrigel assays, respectively. RESULTS: Significantly decreased expression of chemokine receptor 4 (CCR4) was detected in RASF with inhibited E2F2 expression, and the CCR4 expression was increased in RASF with transfection of E2F2-expressing plasmids. Silencing E2F2 expression stimulated apoptosis, but retarded migration and tube-like structure formation in RASF. The opposite observation was obtained in RASF with E2F2 overexpression. CONCLUSIONS: High E2F2 expression decreases apoptosis and increases migration and tube-like structure ability in RASF and might perform this role by up-regulating CCR4 expression, which ultimately contributes to the disease progression of RA synovial tissues. | |
34485183 | Bruton's Tyrosine Kinase Inhibition for the Treatment of Rheumatoid Arthritis. | 2021 | Bruton's tyrosine kinase (BTK) inhibitors are an emerging class of drugs that inhibit B cell receptor activation, FC-γ receptor signaling, and osteoclast proliferation. Following on approval for treatment of hematologic malignancies, BTK inhibitors are now under investigation to treat a number of different autoimmune diseases, including rheumatoid arthritis (RA). While the results of BTK inhibitors in RA animal models have been promising, the ensuing human clinical trial outcomes have been rather equivocal. This review will outline the mechanisms of BTK inhibition and its potential impact on immune mediated disease, the types of BTK inhibitors being studied for RA, the findings from both preclinical and clinical trials of BTK inhibitors in RA, and directions for future research. | |
33643380 | Coupling of Co-expression Network Analysis and Machine Learning Validation Unearthed Poten | 2021 | Rheumatoid arthritis (RA) is an incurable disease that afflicts 0.5-1.0% of the global population though it is less threatening at its early stage. Therefore, improved diagnostic efficiency and prognostic outcome are critical for confronting RA. Although machine learning is considered a promising technique in clinical research, its potential in verifying the biological significance of gene was not fully exploited. The performance of a machine learning model depends greatly on the features used for model training; therefore, the effectiveness of prediction might reflect the quality of input features. In the present study, we used weighted gene co-expression network analysis (WGCNA) in conjunction with differentially expressed gene (DEG) analysis to select the key genes that were highly associated with RA phenotypes based on multiple microarray datasets of RA blood samples, after which they were used as features in machine learning model validation. A total of six machine learning models were used to validate the biological significance of the key genes based on gene expression, among which five models achieved good performances [area under curve (AUC) >0.85], suggesting that our currently identified key genes are biologically significant and highly representative of genes involved in RA. Combined with other biological interpretations including Gene Ontology (GO) analysis, protein-protein interaction (PPI) network analysis, as well as inference of immune cell composition, our current study might shed a light on the in-depth study of RA diagnosis and prognosis. | |
33585033 | A genome-wide association study identifying the SNPs predictive of rapid joint destruction | 2021 Mar | Rheumatoid arthritis (RA) is a common chronic autoimmune disease leading to joint destruction. The aim of the present study was to identify the genomic factors predictive of susceptibility to joint destruction in patients with RA by performing a genome-wide association study of genetic variants, including single nucleotide polymorphisms (SNPs). The study sample included 228 patients with a diagnosis of RA in the past 5 years. Patients were classified into rapid (total Sharp score/years of RA, ≥50) and slow (total Sharp score/years of RA, <50) joint destruction groups for analysis. The association between the genome-wide SNP analysis and joint destruction was evaluated. The following SNPs were strongly associated with rapid radiographic joint destruction: rs2295926 (P<1x10(-7)), belonging to the N-acetylgalactosaminyltransferase 12 (GALNT12) gene and rs11958855 (P<1x10(-6)), belonging to the KCNN2 gene (associated with the potassium calcium-activated channel subfamily). The identification of genetic predictors of rapid joint destruction in RA (GALNT12 and KCNN2) may provide information regarding potential therapeutic targets, and this information may be used to assist in the management RA disease progression, thereby improving the functional outcomes for patients. |