Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 34347945 | Activated Peripheral Blood B Cells in Rheumatoid Arthritis and Their Relationship to Anti- | 2022 Feb | OBJECTIVE: B cells can become activated in germinal center (GC) reactions in secondary lymphoid tissue and in ectopic GCs in rheumatoid arthritis (RA) synovium that may be tumor necrosis factor (TNF) and lymphotoxin (LT) dependent. This study was undertaken to characterize the peripheral B cell compartment longitudinally during anti-TNF therapy in RA. METHODS: Participants were randomized in a 2:1 ratio to receive standard dosing regimens of etanercept (n = 43) or adalimumab (n = 20) for 24 weeks. Eligible participants met the American College of Rheumatology 1987 criteria for RA, had clinically active disease (Disease Activity Score in 28 joints >4.4), and were receiving stable doses of methotrexate. The primary mechanistic end point was the change in switched memory B cell fraction from baseline to week 12 in each treatment group. RESULTS: B cell subsets remained surprisingly stable over the course of the study regardless of treatment group, with no significant change in memory B cells. Blockade of TNF and LT with etanercept compared to blockade of TNF alone with adalimumab did not translate into significant differences in clinical response. The frequencies of multiple activated B cell populations, including CD21- double-negative memory and activated naive B cells, were higher in RA nonresponders at all time points, and CD95+ activated B cell frequencies were increased in patients receiving anti-TNF treatment in the nonresponder group. In contrast, frequencies of transitional B cells-a putative regulatory subset-were lower in the nonresponders. CONCLUSION: Overall, our results support the notion that peripheral blood B cell subsets are remarkably stable in RA and not differentially impacted by dual blockade of TNF and LT with etanercept or single blockade of TNF with adalimumab. Activated B cells do associate with a less robust response. | |
| 35268033 | Improvements in Body Composition after a Proposed Anti-Inflammatory Diet Are Modified by E | 2022 Mar 2 | Rheumatoid Arthritis (RA) is an autoimmune disease affecting peripheral joints. Chronic activation of inflammatory pathways results in decreased function and the development of comorbidities, such as loss of lean mass while retaining total body mass. The objective of this report was to assess whether dietary manipulation affects body composition in patients with RA as a secondary outcome. Fifty patients were included in a randomized controlled crossover trial testing a proposed anti-inflammatory Mediterranean-style diet compared to a Western diet. Body composition was measured by bioelectrical impedance spectroscopy in patients without implants (n = 45). Regardless of treatment, fat-free mass increased and fat mass percentage decreased during weight stability, but no differences between intervention and control in the whole group (n = 42, all p > 0.20) were found. Interaction analysis revealed that participants who were non-employed (n = 15) significantly decreased in fat mass (-1.767 kg; 95% CI: -3.060, -0.475, p = 0.012) and fat mass percentage (-1.805%; 95% CI: -3.024, -0.586, p = 0.008) from the intervention compared to the control period. A Mediterranean-style diet improved body composition in non-employed participants (n = 15). The group as a whole improved regardless of dietary allocation, indicating a potential to treat rheumatoid cachexia by dietary manipulation. | |
| 34923285 | Cost-Effectiveness Analysis of Etanercept 25 mg Maintenance Therapy After Treatment With E | 2022 Mar | OBJECTIVES: To use Markov modeling to estimate the cost-effectiveness of treatment with etanercept 25 mg once weekly plus methotrexate (MTX) in Japanese patients with rheumatoid arthritis who had achieved remission or low disease activity with etanercept 50 mg once weekly plus MTX. METHODS: Effectiveness data were estimated based on results from a clinical trial (PRESERVE) in patients with rheumatoid arthritis who had achieved remission or low disease activity and who were then randomized to receive etanercept 25 mg plus MTX or placebo plus MTX. A Markov model was established and included flare rates of 21% and 62% in the etanercept 25 mg and placebo groups, respectively. EQ-5D was calculated using an ordinary least-squares model that included the health assessment questionnaire disability index and pain visual analog scale. Worsening of the health assessment questionnaire score over 1 year was estimated to be 0.047 for patients with flare, and when associated with radiographic progression it was estimated to increase by 0.006 and 0.025 in the etanercept 25 mg and placebo groups, respectively. A cycle length of 1 year was applied to calculate the cumulative cost and effectiveness for a 10-year time span. RESULTS: Compared with the placebo group, the quality-adjusted life-years for the etanercept 25 mg group was increased by 0.841. The incremental cost-effectiveness ratio was ¥6 173 772. CONCLUSION: These results suggest that maintenance treatment with etanercept 25 mg is cost-effective. | |
| 35572839 | Single-Cell Transcriptome Analysis Reveals the Importance of IRF1/FSTL1 in Synovial Fibrob | 2022 | OBJECTIVES: This study aimed to investigate the potential role of synovial fibroblasts (SFs) in the development of rheumatoid arthritis (RA) to identify potential molecular targets and provide a theoretical basis for the treatment of RA. METHODS: GSE109449, a fibroblast transcriptome dataset of synovial tissue from RA and osteoarthritis (OA), were obtained from the GEO database. After standard cell quality control, this single-cell transcriptome data was used to perform routine single-cell analysis processes. After completing dimensionality reduction, clustering, and cell subset identification of fibroblasts, the SCENIC analysis helped calculate the significant gene regulatory networks in fibroblasts and their subsets. From these computed gene regulatory networks, the regulon in which follistatin-like protein 1 (FSTL1) resides was extracted and used to analyze the transcriptional regulatory status of fibroblasts. Finally, the gene set enrichment analysis (GSEA) was used to calculate the respective enriched gene sets of IRF1 and FSTL1. RESULTS: Three SF subgroups were identified from the single-cell transcriptome analysis; SF subset 3 was more abundant in RA than in OA (p < 0.001). From the SCENIC analysis, we obtained 269 regulons and the corresponding gene regulatory networks in SF from the RA datasets. Next, we screened and obtained a regulon-containing FSTL1, where IRF1 was the major transcription factor. The top five regulons in SF subset 3 were TWIST1, MECOM, KLF6, MAFB, and RUNX1. Among the 3 SF subsets, IRF1 regulon was ranked the highest in SF subset 3. Differential analysis of pseudobulk RNA-seq showed that IRF1 was up-regulated in RA compared to OA. Between the three SF subgroups, IRF1 and FSTL1 expression was more up-regulated in SF subset 3 compared to the other two subgroups. CONCLUSIONS: IRF1 was found to regulate the invasiveness of SFs by regulating FSTL1, which may influence the disease progression of RA. | |
| 33938500 | The Expression Level of FOXO3a in Patients With Autoimmune Diseases: A Meta-analysis. | 2022 Jan 1 | METHODS: PubMed, Web of Science, and China National Knowledge Infrastructure were used to retrieve relevant articles. The pooled standard mean difference with 95% confidence interval was calculated. RESULTS: Totally, 10 studies from 7 publications were included. The levels of FOXO3a were significantly decreased in patients with autoimmune diseases compared with healthy controls (standard mean difference, -1.045; 95% confidence interval, -1.892 to -0.197). When stratified by disease, FOXO3a levels were significantly decreased in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), but were significantly increased in systemic lupus erythematosus. FOXO3a levels of specific tissues or cells in patients with autoimmune diseases were significantly decreased, but no significant difference was observed in the subgroup of peripheral blood mononuclear cells. In the subgroup analysis combining disease and sample, significant differences of FOXO3a were observed in non-PMBCs of RA and IBD patients. CONCLUSIONS: Our study indicated that FOXO3a were significantly decreased in patients with autoimmune diseases. FOXO3a levels was a potential therapeutic target of autoimmune diseases. | |
| 35270012 | Inflammation and Bone Metabolism in Rheumatoid Arthritis: Molecular Mechanisms of Joint De | 2022 Mar 6 | Rheumatoid arthritis (RA) is an inflammatory disease characterized by a variety of symptoms and pathologies often presenting with polyarthritis. The primary symptom in the initial stage is joint swelling due to synovitis. With disease progression, cartilage and bone are affected to cause joint deformities. Advanced osteoarticular destruction and deformation can cause irreversible physical disabilities. Physical disabilities not only deteriorate patients' quality of life but also have substantial medical economic effects on society. Therefore, prevention of the progression of osteoarticular destruction and deformation is an important task. Recent studies have progressively improved our understanding of the molecular mechanism by which synovitis caused by immune disorders results in activation of osteoclasts; activated osteoclasts in turn cause bone destruction and para-articular osteoporosis. In this paper, we review the mechanisms of bone metabolism under physiological and RA conditions, and we describe the effects of therapeutic intervention against RA on bone. | |
| 34607792 | Baseline predictors of different types of treatment success in rheumatoid arthritis. | 2022 Feb | OBJECTIVE: To perform a comprehensive analysis on predictors of achieving disease activity outcomes by change, response and state measures. METHODS: We used data from three rheumatoid arthritis (RA) trials (one for main analysis, two for validation) to analyse the effect of patient and disease characteristics, core set measure and composite indices on the achievement of different outcomes: response outcomes (% of patients achieving a relative response margin); state outcomes (remission or low disease activity, LDA) and change outcomes (numerical change on metric scales). RESULTS: We included patients from the ASPIRE trial (for analysis) and from the ATTRACT and GO-BEFORE trials (for validation). While lower disease activity components at baseline-except acute phase reactants-were associated with achievement of state outcomes (such as LDA by the Simplified Disease Activity Index, SDAI), higher baseline values were associated with change outcomes (such as SDAI absolute change). A multivariate analysis of the identified predictors of state outcomes identified best prediction by a combination of shorter disease duration, male gender and lower disease activity. For prediction of response, no consistently significant predictors were found, again, with exception of C reactive protein, for which higher levels at baseline were associated with better responses. CONCLUSION: Prediction of treatment success is limited in RA. Particularly in early RA, prediction of state targets can be achieved by lower baseline levels of diseases activity. Gender and disease duration may improve the predictability of state targets. In clinical trials, included populations and choice of outcomes can be coordinated to maximise efficiency from these studies. | |
| 35209238 | Functional Analysis of Autoantibody Signatures in Rheumatoid Arthritis. | 2022 Feb 21 | For the identification of antigenic protein biomarkers for rheumatoid arthritis (RA), we conducted IgG profiling on high density protein microarrays. Plasma IgG of 96 human samples (healthy controls, osteoarthritis, seropositive and seronegative RA, n = 24 each) and time-series plasma of a pristane-induced arthritis (PIA) rat model (n = 24 total) were probed on AIT's 16k protein microarray. To investigate the analogy of underlying disease pathways, differential reactivity analysis was conducted. A total of n = 602 differentially reactive antigens (DIRAGs) at a significance cutoff of p < 0.05 were identified between seropositive and seronegative RA for the human samples. Correlation with the clinical disease activity index revealed an inverse correlation of antibodies against self-proteins found in pathways relevant for antigen presentation and immune regulation. The PIA model showed n = 1291 significant DIRAGs within acute disease. Significant DIRAGs for (I) seropositive, (II) seronegative and (III) PIA were subjected to the Reactome pathway browser which also revealed pathways relevant for antigen presentation and immune regulation; of these, seven overlapping pathways had high significance. We therefore conclude that the PIA model reflects the biological similarities of the disease pathogenesis. Our data show that protein array analysis can elucidate biological differences and pathways relevant in disease as well be a useful additional layer of omics information. | |
| 35220565 | Long Non-coding RNAs in Rheumatology. | 2022 | The last decade has seen an enormous increase in long non-coding RNA (lncRNA) research within rheumatology. LncRNAs are arbitrarily classed as non-protein encoding RNA transcripts that exceed 200 nucleotides in length. These transcripts have tissue and cell specific patterns of expression and are implicated in a variety of biological processes. Unsurprisingly, numerous lncRNAs are dysregulated in rheumatoid conditions, correlating with disease activity and cited as potential biomarkers and targets for therapeutic intervention. In this chapter, following an introduction into each condition, we discuss the lncRNAs involved in rheumatoid arthritis, osteoarthritis and systemic lupus erythematosus. These inflammatory joint conditions share several inflammatory signalling pathways and therefore not surprisingly many commonly dysregulated lncRNAs are shared across these conditions. In the interest of translational research only those lncRNAs which are strongly conserved have been addressed. The lncRNAs discussed here have diverse roles in regulating inflammation, proliferation, migration, invasion and apoptosis. Understanding the molecular basis of lncRNA function in rheumatology will be crucial in fully determining the inflammatory mechanisms that drive these conditions. | |
| 34344706 | Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate | 2022 Apr | OBJECTIVE: To evaluate the efficacy and safety of olokizumab (OKZ) in patients with active rheumatoid arthritis despite treatment with methotrexate (MTX). METHODS: In this 24-week multicentre, placebo-controlled, double-blind study, patients were randomised 1:1:1 to receive subcutaneously administered OKZ 64 mg once every 2 weeks, OKZ 64 mg once every 4 weeks, or placebo plus MTX. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. The secondary efficacy endpoints included percentage of subjects achieving Disease Activity Score 28-joint count based on C reactive protein <3.2, Health Assessment Questionnaire Disability Index at week 12, ACR50 response and Clinical Disease Activity Index ≤2.8 at week 24. Safety and immunogenicity were assessed throughout the study. RESULTS: A total of 428 patients were randomised. ACR20 responses were more frequent with OKZ every 2 weeks (63.6%) and OKZ every 4 weeks (70.4%) than placebo (25.9%) (p<0.0001 for both comparisons). There were significant differences in all secondary efficacy endpoints between OKZ-treated arms and placebo. Treatment-emergent serious adverse events (TESAEs) were reported by more patients in the OKZ groups compared with placebo. Infections were the most common TESAEs. No subjects developed neutralising antidrug antibodies. CONCLUSIONS: Treatment with OKZ was associated with significant improvement in signs, symptoms and physical function of rheumatoid arthritis without discernible differences between the two regimens. Safety was as expected for this class of agents. Low immunogenicity was observed. Trial registration number NCT02760368. | |
| 35012522 | Exploring drug cost and disease outcome in rheumatoid arthritis patients treated with biol | 2022 Jan 10 | BACKGROUND: In Norway, an annual tender system for the prescription of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) has been used since 2007. This study aimed to explore annual b/tsDMARDs costs and disease outcomes in Norwegian rheumatoid arthritis (RA) patients between 2010 and 2019 under the influence of the tender system. METHODS: RA patients monitored in ordinary clinical practice were recruited from 10 Norwegian centers. Data files from each center for each year were collected to explore demographics, disease outcomes, and the prescribed treatment. The cost of b/tsDMARDs was calculated based on the drug price given in the annual tender process. RESULTS: The number of registered RA patients increased from 4909 in 2010 to 9335 in 2019. The percentage of patients receiving a b/tsDMARD was 39% in 2010 and 45% in 2019. The proportion of b/tsDMARDs treated patients achieving DAS28 remission increased from 42 to 67%. The estimated mean annual cost to treat a patient on b/tsDMARDs fell by 47%, from 13.1 thousand euros (EUR) in 2010 to 6.9 thousand EUR in 2019. The mean annual cost to treat b/tsDMARDs naïve patients was reduced by 75% (13.0 thousand EUR in 2010 and 3.2 thousand EUR in 2019). CONCLUSIONS: In the period 2010-2019, b/tsDMARD treatment costs for Norwegian RA patients were significantly reduced, whereas DAS28 remission rates increased. Our data may indicate that the health authorities' intention to reduce treatment costs by implementing a tender system has been successful. | |
| 34142111 | Efficacy and safety of switching from reference adalimumab to CT-P17 (100 mg/ml): 52-week | 2022 Apr 11 | OBJECTIVE: To compare the safety and efficacy of switching from reference adalimumab to adalimumab biosimilar CT-P17 with continuing reference adalimumab/CT-P17 in active RA. METHODS: This double-blind, phase III study randomized (1:1) subjects with active RA to receive 40 mg (100 mg/ml) CT-P17 or European Union-sourced reference adalimumab subcutaneously every 2 weeks (Q2W) until week (W) 24 [treatment period (TP) 1]. Thereafter, subjects receiving reference adalimumab were randomized (1:1) to continue reference adalimumab or switch to CT-P17 from W26 (both Q2W until W48; TP2). Subjects receiving CT-P17 in TP1 continued CT-P17. W0-W24 results were previously reported; we present W26-W52 findings. End points were efficacy (including joint damage progression), pharmacokinetics, safety and immunogenicity. RESULTS: Of 607 subjects who initiated TP2 treatment, 303 continued CT-P17, 153 continued reference adalimumab and 151 switched to CT-P17. Efficacy improvements up to W24 were maintained during TP2; efficacy was comparable among groups. At W52, 20% improvement in ACR response rates were 80.5% (continued CT-P17), 77.8% (continued reference adalimumab) and 82.2% (switched to CT-P17). Joint damage progression was minimal. Mean trough serum adalimumab concentrations were similar among groups. CT-P17 and reference adalimumab safety profiles were numerically similar and switching did not affect immunogenicity. At W52, 28.4% (continued CT-P17), 27.0% (continued reference adalimumab) and 28.3% (switched to CT-P17) of subjects were anti-drug antibody-positive. CONCLUSION: Efficacy, pharmacokinetics, safety and immunogenicity of CT-P17 and reference adalimumab were comparable after 1 year of treatment, including after switching from reference adalimumab to CT-P17. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT03789292. | |
| 35211187 | Maximal Information Coefficient-Based Testing to Identify Epistasis in Case-Control Associ | 2022 | Interactions between genetic variants (epistasis) are ubiquitous in the model system and can significantly affect evolutionary adaptation, genetic mapping, and precision medical efforts. In this paper, we proposed a method for epistasis detection, called EpiMIC (epistasis detection through a maximal information coefficient (MIC)). MIC is a promising bivariate dependence measure explicitly designed for rapidly exploring various function types equally and for interpreting and comparing them on the same scale. Most epistasis detection approaches make assumptions about the form of the association between genetic variants, resulting in limited statistical performance. Based on the notion that if two SNPs do not interact, their joint distribution in all samples and in only cases should not be substantially different. We developed a statistic that utilizes the difference of MIC as a signal of epistasis and combined it with a permutation resampling strategy to estimate the empirical distribution of our statistic. Results of simulation and real-world data set showed that EpiMIC outperformed previous approaches for identifying epistasis at varying degrees of heredity. | |
| 35287902 | Targeted delivery of methotrexate by modified yeast β-glucan nanoparticles for rheumatoid | 2022 May 15 | The linear β-(1, 3)-glucans from yeast (BYGs) with good biocompatibility and targetability to macrophages were used for fabricating BYG-based nanoparticles to deliver methotrexate with systemic toxicity for treatment of rheumatoid arthritis. Methoxy poly (ethylene glycol) (mPEG) was successfully grafted onto BYGs chains, followed by chemical crosslinking to get the crosslinked copolymer (cBP) with amphiphilicity, which could self-assemble into spherical nanoparticles (ca.52.9 nm in diameter). The methotrexate-loaded cBP nanoparticles (cBPM) with the drug loading efficiency of 23.7% was proved to linearly release methotrexate due to reduction of disulfide bonds by glutathione. Cell experiments demonstrate that cBP nanoparticles were effectively internalized into macrophages due to the targetability. Animal experiments show that cBPM were highly targeted to the inflamed tissue, leading to macrophage transformation from M1 to M2 type and reduction of pro-inflammatory factors. This work provides an alternative safe strategy for the clinical treatment of rheumatoid arthritis with β-glucan nanoparticles as carrier. | |
| 35112979 | Long non-coding RNA TSPEAR Antisense RNA 2 is downregulated in rheumatoid arthritis and in | 2022 Feb | Long non-coding RNA (lncRNA) TSPEAR-AS2 (TSPEAR Antisense RNA 2) participates in many human diseases, while its roles in rheumatoid arthritis (RA) are unknown. Plasma expression levels of TSPEAR-AS2 and microRNA (miR)-212-3p in both RA patients and healthy controls were measured by RT-qPCR. Diagnostic potentials of plasma TSPEAR-AS2 and miR-212-3p were assessed by ROC curve analysis. Normalized expression levels of TSPEAR-AS2 and miR-212-3p were subjected to Pearson's correlation coefficient to evaluate their corrections. TSPEAR-AS2 was significantly downregulated in RA patients, while plasma expression levels of miR-212-3p were significantly increased in RA patients. The expression of TSPEAR-AS2 and miR-212-3p showed promising diagnostic value for RA. Plasma expression levels of TSPEAR-AS2 and miR-212-3p were significantly and inversely correlated in RA patients but not in healthy controls. Besides, overexpression of TSPEAR-AS2 decreased the apoptosis of RA HFLSs, while miR-212-3p increased cell apoptosis. In addition, miR-212-3p attenuated the effects of overexpression of TSPEAR-AS2. Overexpression of TSPEAR-AS2 decreased the expression levels of miR-212-3p in HFLS, while overexpression of miR-212-3p did not affect the expression of TSPEAR-AS2. In conclusion, TSPEAR-AS2 is downregulated in RA and its overexpression can decrease the apoptosis of RA HFLSs by downregulating miR-212-3p. | |
| 34904598 | Folate-modified triptolide liposomes target activated macrophages for safe rheumatoid arth | 2022 Jan 18 | Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial joint hyperplasia, joint inflammation, cartilage erosion and bone destruction. Macrophages play an essential role in the pathogenesis of RA, and folate receptor β (FR-β) is highly expressed on the surface of activated synovial macrophages in RA patients. Triptolide (TP) has anti-inflammatory properties, and it can protect the cartilage matrix, but its clinical application has been limited due to poor solubility, low bioavailability and systemic toxicity. Therefore, we constructed folate-modified triptolide liposomes (FA-TP-Lips) to target macrophages, thereby treating RA in a safe and effective way. The experiments indicated that FA-TP-Lips had properties of small particle size, uniform particle size distribution, high drug encapsulation and long circulation. Furthermore, FA-TP-Lips showed reduced cytotoxicity, increased cellular uptake and significant anti-inflammatory effects in vitro. It also inhibited osteoclastogenesis. In vivo experiments revealed that liposomes could prolong the circulation of TP in the body, as well as exhibit significant cartilage-protective and anti-inflammatory effects with lower toxicity compared with the free TP group, thereby providing a promising new approach for the treatment of RA. | |
| 34688020 | Systemic effects of IL-6 blockade in rheumatoid arthritis beyond the joints. | 2022 Jan | Interleukin (IL)-6 is produced locally in response to an inflammatory stimulus, and is able to induce systemic manifestations at distance from the site of inflammation. Its unique signaling mechanism, including classical and trans-signaling pathways, leads to a major expansion in the number of cell types responding to IL-6. This pleiotropic cytokine is a key factor in the pathogenesis of rheumatoid arthritis (RA) and is involved in many extra-articular manifestations that accompany the disease. Thus, IL-6 blockade is associated with various biological effects beyond the joints. In this review, the systemic effects of IL-6 in RA comorbidities and the consequences of its blockade will be discussed, including anemia of chronic disease, cardiovascular risks, bone and muscle functions, and neuro-psychological manifestations. | |
| 35367217 | Mechanism of Lycopodii herba for RA-ILD using integrated metabolomics and network pharmaco | 2022 Jul 1 | Interstitial lung disease (ILD) is the most common complication of rheumatoid arthritis (RA), which highly increases the morbidity and mortality of RA. Lycopodii herba (SJC) has been used as a widespread traditional Chinese medicine to treat RA and the related complications for more than 500 years. However, its therapeutic effect on RA-ILD and related mechanisms are not clear. The purpose of this work was to confirm the efficacy of SJC for RA-ILD and clarify its mechanism. In this study, we first determined the efficacy of SJC on RA-ILD. Then, 15 potential biomarkers of SJC were identified by metabolomics in rat serum, which were mainly associated with ether lipid metabolism and arachidonic acid metabolism. 21 pathways were related to SJC by network pharmacology. Combined with the results of metabolomics and network pharmacology and real-time PCR (RT-PCR) validation, the mechanism of SJC for RA-ILD may be related to the Ras signaling pathway and PI3K-Akt signaling pathway by regulating the expression of PLA2G1B and PI3KCA. This work preliminary confirmed the preventive and therapeutic effects of SJC on RA-ILD and elucidated the mechanism from the metabolic perspective. | |
| 34561701 | Long-term use of glucocorticoid exacerbates bone lesions in postmenopausal women with rheu | 2022 Jan 7 | Glucocorticoid-induced osteoporosis is osteoporosis arising due to long-term use of glucocorticoids. Despite decades of intense research, the effects of long-term use of glucocorticoids in humans on bone cells and bone structural changes remain unclear. We performed post-mortem histomorphometric analysis of bone from two female patients with rheumatoid arthritis aged 64 and 85 years. Our two patients had been treated with glucocorticoids for 19 and 14 years, respectively. In Case 1, all markers of cancellous bone volume were markedly decreased compared with the age-matched reference range. Connectivity of cancellous bone trabecula was absent. Only a few island bones were noted. There was prominent thinning of the cortical bone and extension of the bone marrow cavity into the cortical bone with prominent cortical porosis. Cortical nodes between the endocortical surface and the trabecula disappeared due to endocortical resorption. Stoppage of lamellar structure was observed because the bone resorption by osteoclasts surpassed bone formation by osteoblasts. Empty lacunae characterised by disappearance of osteocytes were visible. In Case 2, all volume markers of cancellous bone were decreased to the same extent as Case 1. However, cortical porosis was more prominent than Case 1. These two cases suggest that use of glucocorticoid therapy >10 years can induce severe osteoporosis in elderly rheumatoid arthritis women with higher disease activity and that the disappearance of cancellous bone is the common characteristic. The 85-year-old woman was characterised by cortical porosis. | |
| 33356682 | Association of Toll-like Receptor 4 Rs7873784 G/C Polymorphism with Rheumatoid Arthritis R | 2022 Apr | BACKGROUND: The purposes of this study were to explore whether the Toll-like receptor 4 (TLR4) gene rs7873784 G/C polymorphism was related to the risk of rheumatoid arthritis (RA) and to the clinical features of the disease in Chinese subjects. MATERIALS AND METHODS: We examined the TLR4 rs7873784 G/C polymorphism in 805 Chinese RA patients and 1095 healthy controls. Genotype was determined with a custom-by-design 48-Plex single nucleotide polymorphism scan™ Kit. Blood plasma levels of TLR4 in 170 RA patients and 170 matched controls were measured by ELISA. RESULTS: The TLR4 gene rs7873784 G/C polymorphism was related to a reduced risk for RA. By stratified analysis, we found a dramatically reduced risk for RA in patients who were female, CRP-positive, RF-positive, DAS28 ≥ 3.20, or ESR ≥ 25. Compared with the controls, the average level of TLR4 protein in plasma of RA patients was increased. In addition, RA patients exhibited higher levels of TLR4 mRNA than controls (P < .05). CONCLUSION: These results demonstrate the TLR4 rs7873784 G/C polymorphism to relate to a decreased risk for RA in a Chinese population. |