Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 35321875 | Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrull | 2022 Mar | BACKGROUND: Rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) are important biomarkers for diagnosis of rheumatoid arthritis (RA). However, there is poor harmonisation of RF and ACPA assays. The aim of this study was to refine RF and ACPA interpretation across commercial assays. MATERIALS AND METHODS: Six total RF isotype-non-specific assays, 3 RF IgM isotype-specific assays and 9 ACPA immunoglobulin G assays of 13 different companies were evaluated using 398 diagnostic samples from patients with RA and 1073 disease controls. RESULTS: Using cut-offs proposed by the manufacturer, there was a large variability in diagnostic sensitivity and specificity between assays. Thresholds of antibody levels were determined based on predefined specificities and used to define test result intervals. Test result interval-specific likelihood ratios (LRs) were concordant across the different RF and ACPA assays. For all assays, the LR for RA increased with increasing antibody level. Higher LRs were found for ACPA than for RF. ACPA levels associated with LRs >80 were found in a substantial fraction (>22%) of patients with RA. CONCLUSION: Defining thresholds for antibody levels and assigning test result interval-specific LRs allows alignment of clinical interpretation for all RF and ACPA assays. | |
| 35000008 | Mendelian randomization study on the causal effects of omega-3 fatty acids on rheumatoid a | 2022 May | OBJECTIVES: To resolve the ongoing debate on the role of plasma omega-3 fatty acids in rheumatoid arthritis (RA), we attempted to identify the association between omega-3 intake and the risk of RA. METHODS: We analyzed data from the largest genome-wide association study (GWAS) for omega-3 fatty acids (N = 114,999 of European ancestry) and RA (14,361 cases and 43,923 controls of European ancestry). Mendelian randomization-egger_intercept, MR-PRESSO, and Cochran's Q test were used to determine pleiotropy and heterogeneity. Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode were used to evaluate the causal association of plasma omega-3 levels on RA. RESULTS: We found no significant pleiotropy, heterogeneity, and bias among the omega-3 genetic instrumental variables (IVs) in RA GWAS datasets. MR analysis demonstrated that as omega-3 levels genetically increased, the risk of MS increased using MR-egger (Beta = 0.137, p = 0.037; OR = 1.146, 95% CI: [1.014, 1.296]), weighted median (Beta = 0.162, p = 0.001; OR = 1.176, 95% CI: [1.070, 1.292]), IVW (Beta = 0.102, p = 0.025; OR = 1.108, 95% CI: [1.013, 1.211]), simple mode (Beta = 0.219, p = 0.149; OR = 1.245, 95% CI: [0.931, 1.665]), and weighted mode (Beta = 0.146, p = 0.006; OR = 1.157, 95% CI: [1.051, 1.274]). CONCLUSIONS: Our analysis suggested a causal association between genetically increased plasma omega-3 levels and the increased risk of RA in populations with European ancestry. Thus, to reduce the risk of RA, those of European descent should reduce omega-3 intake. Key Points • No significant pleiotropy or heterogeneity among the omega-3 genetic IVs in RA GWAS datasets. • Genetically increased plasma omega-3 levels enhanced the risk of RA in European lineages. | |
| 34983485 | Simultaneous occurrence of accelerated nodulosis in lungs, liver, and kidneys, and acute e | 2022 Jan 5 | BACKGROUND: Accelerated nodulosis (ARN) is a rare variant of rheumatoid nodules (RNs) that is characterized by a rapid onset or the worsening of RNs. It generally develops at the fingers in patients with rheumatoid arthritis (RA) receiving methotrexate (MTX). Few case reports have described ARN at an extracutaneous location. CASE PRESENTATION: An elderly patient with long-standing RA was admitted to our hospital with acute respiratory failure. Computed tomography upon admission showed diffuse ground-glass opacities superimposed with subpleural reticular shadowing and honeycombing and multiple nodules in the lungs and liver. Despite the discontinuation of MTX and introduction of an immunosuppressive regimen with pulse methylprednisolone followed by a tapering dose of prednisolone and intravenous cyclophosphamide, the patient died due to the acute exacerbation (AE) of RA-related interstitial lung disease (ILD) following the parallel waxing and waning of a diffuse interstitial shadow and pulmonary and liver nodules. At autopsy, RNs were scattered throughout both lung fields in addition to extensive interstitial changes. RNs were also detected in the liver and kidneys. The foci of cryptococcosis were mainly identified in alveolar spaces. Based on the clinical and pathological findings, these nodules were most consistent with ARN because of acute increases in the size and number of previously detected pulmonary nodules. CONCLUSION: The present case is noteworthy because ARN was concurrently detected in multiple internal organs and may be associated with the AE of RA-related ILD. | |
| 34480694 | Inflammatory macrophages exacerbate neutrophil-driven joint damage through ADP/P2Y(1) sign | 2022 May | Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints and is associated with excessive immune cell infiltration. However, the complex interactions between the immune cell populations in the RA synovium remain unknown. Here, we demonstrate that inflammatory macrophages in the synovium exacerbate neutrophil-driven joint damage in RA through ADP/P2Y(1) signaling. We show that extracellular ADP (eADP) and its receptors are obviously increased in synovial tissues of RA patients as well as collagen-induced arthritis (CIA) mice, and eADP enhances neutrophil infiltration into joints through macrophages producing the chemokine CXCL2, aggravating disease development. Accordingly, the arthritis mouse model had more neutrophils in inflamed joints following ADP injection, whereas P2Y(1) deficiency and pharmacologic inhibition restored arthritis severity to basal levels, suggesting a dominant role of ADP/P2Y(1) signaling in RA pathology. Moreover, cellular activity of ADP/P2Y(1)-mediated CXCL2 production was dependent on the G(αq)/Ca(2+)-NF-κB/NFAT pathway in macrophages. Overall, this study reveals a non-redundant role of eADP as a trigger in the pathogenesis of RA through neutrophil recruitment and disrupted tissue homeostasis and function. | |
| 34362290 | Emerging role of leptin in joint inflammation and destruction. | 2022 Mar | Rheumatoid arthritis (RA) is an autoimmune disease characterized by tumor-like hyperplasia and inflammation of the synovium, which causes synovial cell invasion into the bone and cartilage. In RA pathogenesis, various molecules in effector cells (i.e., immune cells and mesenchymal cells) are dysregulated by genetic and environmental factors. Consistent with the early stages of RA, these pathogenic cells cooperate and activate each other directly by cell-to-cell contact or indirectly via humoral factors. Recently, growing evidence has revealed essential role of adipokines, which are multifunctional signal transduction molecules, in the immune system. In this review, we summarize the current understanding of the cross-talk between leptin, one of the most well-known and best-characterized adipokines, and osteoimmunology. Furthermore, we discuss the contribution of leptin to the pathogenesis of RA and its potential mechanisms. | |
| 35070497 | Beneficial autoimmunity and maladaptive inflammation shape epidemiological links between c | 2022 | Chronic inflammation drives proliferative responses, hence increasing cellular multiplication with the consequent risk of malignant transformation. Autoimmune responses against self-antigens drive chronic inflammation but may also enhance cancer immunosurveillance with the consequent reduction of tumor incidence and progression. These notions, which have been well established at the preclinical level, may explain the generally positive associations between immune-inflammatory diseases but also some negative associations, for example between breast cancer and rheumatoid arthritis or systemic lupus erythematosus, which have recently been confirmed in a study enrolling close to half a million participants from the UK Biobank. | |
| 35216226 | Proinflammatory Cytokines (IL-1, -6, -8, -15, -17, -18, -23, TNF-α) Single Nucleotide Pol | 2022 Feb 14 | Conducted studies highlight that a mixture of genetic and environmental factors is responsible for rheumatoid arthritis (RA) development. This study aimed to analyze the available literature for the relationship between, on the one hand, single-nucleotide polymorphisms (SNPs) in the proinflammatory cytokines genes interleukin-1 (IL-1), -6, -8, -15, -17, -18, and -23, and tumor necrosis factor-alpha (TNF-α), and on the other hand, RA susceptibility, severity, and patients' response to applied treatment. The PubMed database was searched for sources. Preference was given to articles which were published within the past 20 years. Data indicate that the relationship between selected SNPs in proinflammatory cytokines genes and susceptibility to developing RA is inconclusive, and it depends on the ethnicity of the population. Although the allelic and genotypic frequencies of many SNPs in proinflammatory cytokines genes analyzed did not differ between RA patients and healthy controls, deeper analysis showed that these polymorphisms have a relationship with clinicopathological features of RA. SNPs in proinflammatory cytokines genes also "modify patients' response" to applied treatment. Further studies, on larger cohorts of subjects and in different populations, should be conducted to elucidate the role of SNPs in IL-1, -6, -8, -15, -17, -18, and -23, and TNF-α genes in RA patients. | |
| 33853484 | Systematic review for the treatment of older rheumatoid arthritis patients informing the 2 | 2022 Feb 28 | OBJECTIVES: To provide an evidence base for clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA) in older adults. METHODS: PubMed, Cochrane library, and Japan Centra Revuo Medicina databases were searched for articles published between 1990 and 2019. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system, with some modifications. RESULTS: Among 702 identified articles, there were 5 post-hoc analyses of randomized controlled trials and 10 observational studies. Meta-analysis of the former yielded a mean difference of the van der Heijde-modified total Sharp score of -2.79 (95% confidence interval [CI] - 3.74 to -1.84) for treatment with tumor necrosis factor inhibitors. The risk ratio (RR) for the American College of Rheumatology 50% response rate, and for serious adverse events was 2.83 (95%CI 1.90-4.21) and 1.32 (95%CI 0.53-3.31), respectively, for Janus kinase inhibitors. Meta-analysis of the observational studies yielded an RR for disease activity score-28 remission and serious infections of 0.76 (95%CI 0.64-0.91) and 1.92 (95%CI 1.31-2.81) for older-versus-younger patients receiving biological disease-modifying antirheumatic drugs, respectively. CONCLUSION: This systematic review provides the necessary evidence for developing CPG for the management of RA in older adults. | |
| 33483748 | TNFα induces endothelial dysfunction in rheumatoid arthritis via LOX-1 and arginase 2: re | 2022 Jan 7 | AIMS: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting joints and blood vessels. Despite low levels of low-density lipoprotein cholesterol (LDL-C), RA patients exhibit endothelial dysfunction and are at increased risk of death from cardiovascular complications, but the molecular mechanism of action is unknown. We aimed in the present study to identify the molecular mechanism of endothelial dysfunction in a mouse model of RA and in patients with RA. METHODS AND RESULTS: Endothelium-dependent relaxations to acetylcholine were reduced in aortae of two tumour necrosis factor alpha (TNFα) transgenic mouse lines with either mild (Tg3647) or severe (Tg197) forms of RA in a time- and severity-dependent fashion as assessed by organ chamber myograph. In Tg197, TNFα plasma levels were associated with severe endothelial dysfunction. LOX-1 receptor was markedly up-regulated leading to increased vascular oxLDL uptake and NFκB-mediated enhanced Arg2 expression via direct binding to its promoter resulting in reduced NO bioavailability and vascular cGMP levels as shown by ELISA and chromatin immunoprecipitation. Anti-TNFα treatment with infliximab normalized endothelial function together with LOX-1 and Arg2 serum levels in mice. In RA patients, soluble LOX-1 serum levels were also markedly increased and closely related to serum levels of C-reactive protein. Similarly, ARG2 serum levels were increased. Similarly, anti-TNFα treatment restored LOX-1 and ARG2 serum levels in RA patients. CONCLUSIONS: Increased TNFα levels not only contribute to RA, but also to endothelial dysfunction by increasing vascular oxLDL content and activation of the LOX-1/NFκB/Arg2 pathway leading to reduced NO bioavailability and decreased cGMP levels. Anti-TNFα treatment improved both articular symptoms and endothelial function by reducing LOX-1, vascular oxLDL, and Arg2 levels. | |
| 34387761 | Blockade of adiponectin receptor 1 signaling inhibits synovial inflammation and alleviates | 2022 Jan | OBJECTIVES: Adiponectin (AD) highly expressed in synovial tissue correlates closely with progressive bone erosion in rheumatoid arthritis (RA). However, it remains unknown whether AD receptor mediates the pathogenesis of RA. This study aimed to investigate the effects of adiponectin receptor 1 (AdipoR1) signaling on synovial inflammation and joint damage in collagen-induced arthritis. METHODS: AD and AdipoR1 expression in synovial tissue of RA and osteoarthritis (OA) patients were tested by PCR and western blotting. The frequency of AdipoR1 on RA synovial fibroblasts (RASFs) was examined by flow cytometry after stimulation with AD, IL-6, or TNF-α. AdipoR1 was knocked down in human RASF cell line (MH7A) and CIA mice joints using lentiviral particles carrying the AdipoR1 short hairpin RNA (shAdipoR1). Both the proliferation and apoptosis of MH7A and the secretion of inflammatory factors from MH7A were examined in vitro. The therapeutic effect of local AdipoR1 inhibition on CIA mice was assessed in vivo. RESULTS: Both the expression of AD and AdipoR1 were significantly higher in RA synovial tissue. AdipoR1 on RASFs was upregulated by AD. Silencing AdipoR1 remarkably reduced lipopolysaccharides-induced proliferation and promoted the apoptosis of MH7A. Moreover, AdipoR1 knockdown inhibited the release of inflammatory factors in vitro. In CIA mice, local AdipoR1 inhibition effectively decreased joint inflammation and alleviated bone destruction via suppressing RANKL and RANKL/OPG ratio in vivo. CONCLUSIONS: AdipoR1 signaling participates in the process of synovial inflammation and joint damage in CIA. Local blockade of AdipoR1 might be a new target for the clinical treatment of RA. Key points • Local AdipoR1 inhibition decreased joint inflammation and alleviated bone destruction in CIA. | |
| 35355986 | The Neuroimmune Interplay in Joint Pain: The Role of Macrophages. | 2022 | Chronic pain associated with joint disorders, such as rheumatoid arthritis (RA), osteoarthritis (OA) and implant aseptic loosening (AL), is a highly debilitating symptom that impacts mobility and quality of life in affected patients. The neuroimmune crosstalk has been demonstrated to play a critical role in the onset and establishment of chronic pain conditions. Immune cells release cytokines and immune mediators that can activate and sensitize nociceptors evoking pain, through interaction with receptors in the sensory nerve terminals. On the other hand, sensory and sympathetic nerve fibers release neurotransmitters that bind to their specific receptor expressed on surface of immune cells, initiating an immunomodulatory role. Macrophages have been shown to be key players in the neuroimmune crosstalk. Moreover, macrophages constitute the dominant immune cell population in RA, OA and AL. Importantly, the targeting of macrophages can result in anti-nociceptive effects in chronic pain conditions. Therefore, the aim of this review is to discuss the nature and impact of the interaction between the inflammatory response and nerve fibers in these joint disorders regarding the genesis and maintenance of pain. The role of macrophages is highlighted. The alteration in the joint innervation pattern and the inflammatory response are also described. Additionally, the immunomodulatory role of sensory and sympathetic neurotransmitters is revised. | |
| 34741249 | Evaluation of a multidisciplinary care model to improve quality of life in rheumatoid arth | 2022 Jun | BACKGROUND AND PURPOSE: Health-Related Quality of Life (HR-QOL) is an important patient-reported domain in patients with rheumatoid arthritis (RA). The uptake of multidisciplinary team (MDT) care in RA is generally low, due to initial high demand for resources. We hypothesised that whilst pharmacological treatments are effective in controlling disease activity, a multipronged intervention in an MDT may have a positive impact on HR-QOL. METHODS: This was a single-centre randomized parallel group, single-blind controlled trial of MDT vs. usual care in an established RA clinic. Data were collected through face-to-face questionnaires, medical records review, and joint counts by a blinded assessor at 0, 3 and 6Â months. Adult RA patients were randomly assigned in a single visit to a 6-member MDT (rheumatologist, nurse, social worker, physiotherapist, occupational therapist, and podiatrist) or usual care. MDT providers prescribed medications and counselled patients on managing flares, medication adherence, coping, joint protection, exercise, footwear. The primary outcome was minimal clinically important difference (MCID) in HR-QOL (increase in European QOL-5-Dimension-3-Level, EQ-5D-3L by 0.1) at six months. RESULTS: 140 patients (86.3% female, 53.4% Chinese, median (IQR) age 56.6 (46.7, 62.4) years); 70 were randomized to each arm. Median (IQR) disease duration was 5.5 (2.4, 11.0) years and disease activity in 28 joints (DAS28) was 2.87 (2.08, 3.66). 123 patients completed the study. Twenty-six (40.6%) MDT vs. 23 (34.3%) usual care patients achieved an MCID in EQ-5D-3L, OR 1.3 (0.6, 2.7). In multivariable logistic regression, baseline EQ-5D-3L was the only predictor of achieving MCID. There was more disease modifying anti-rheumatic drug escalation in MDT (34.4% vs. 19.4%). Patients with high disease activity were more likely to achieve MCID in the MDT arm. CONCLUSIONS: A single visit by stable patients with low disease activity to an MDT failed to achieve MCID in the EQ-5D-3L; however, did achieve small but significant improvements in the EQ-5D-3L, DAS28, pain, coping and self-efficacy. To be sustainable, MDT care should be targeted at patients with high disease activity or those with a new diagnosis of RA. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov, identifier: NCT03099668. | |
| 35585215 | Long-term drug effectiveness and survival for reference rituximab in rheumatoid arthritis | 2022 May 18 | To explore the long-term drug effectiveness and survival of reference rituximab (ref-RTX)-treated rheumatoid arthritis (RA) patients in an ordinary outpatient clinic. Second, we explored baseline predictors of drug effectiveness and survival, and third, we clarified reasons for stopping treatment. RA patients treated with ref-RTX between 2006 and 2020 in Norway were examined and monitored using recommended measures for disease activity and patient-reported outcomes (PROs). Drug effectiveness was assessed with random intercept linear mixed models; drug survival was assessed with Kaplan-Meier survival analysis. Reasons for discontinuation were ascertained. Baseline predictors of drug effectiveness and survival were estimated. Among 246 RA patients, at baseline, 17.1% were biologic disease-modifying anti-rheumatic drugs (bDMARDs) naïve, and 51.6% were currently using conventional synthetic DMARDs (csDMARDs). During the five-year follow-up, all disease activity and PRO measures improved significantly (p < 0.01), with more substantial changes noted in the second year. Drug survival was 83% after one year and declined to 34% after five years. The two most frequently reported reasons for discontinuation were the doctor's decision (36.2%) and lack or loss of effectiveness (19.2%). No significant difference was found between naïve and previous users of bDMARDs or between concomitant and nonconcomitant users of csDMARDs when analysing drug effectiveness and survival. Our real-life data show that ref-RTX-treated RA patients had satisfactory treatment responses; drug survival declined linearly over time. There was no significant difference between naïve and previous users of bDMARDs or between concomitant and nonconcomitant users of csDMARDs, both for drug effectiveness and survival. | |
| 34375179 | PCSK9 and Inflammation: Their Role in Autoimmune Diseases, with a Focus on Rheumatoid Arth | 2022 | Despite a clear epidemiological link between autoimmune disease and cardiovascular (CV) risk exists, pathophysiological explanations are extremely complex and far from being elucidated. Dysregulation of metabolic pathways and chronic low-grade inflammation represent common pathways, but CV risk still remains underestimated in patients with autoimmune diseases. Among different candidate mediators, pro-protein convertase subtilisin/kexin type 9 (PCSK9) is attracting growing attention, due to a combined effect on lipid metabolism and inflammatory response. Studies on PCSK9 inhibitors have established a clear benefit on CV outcome without an established effect on inflammation. Conversely, evidence from sepsis and HIV infection strongly supports a pro-inflammatory role of PCSK9. Still, the role of PCSK9 in autoimmune diseases is uncertain. So far, reported clinical findings are controversial and likely reflect the poor knowledge of PCSK9 activity on monocyte/macrophage migration and activation. The complex signaling network around PCSK9 synthesis and metabolism may also have a role, especially concerning the involvement of scavenger receptors, such as CD36. Such complexity in PCSK9 signaling seems particularly evident in autoimmune disease model. This would also potentially explain the observed independency between lipid profile and PCSK9 levels, the so-called "lipid paradox". In this narrative review, we will summarize the current knowledge about the complex network of PCSK9 signaling. We will focus on upstream and downstream pathways with potential implication in autoimmune disease and potential effects of PCSK9 inhibiting strategies. | |
| 35185895 | Pegylation Reduces the Uptake of Certolizumab Pegol by Dendritic Cells and Epitope Present | 2022 | Pegylation of biopharmaceuticals is the most common strategy to increase their half-life in the blood and is associated with a reduced immunogenicity. As antigen presentation is a primary event in the activation of CD4 T-cells and initiation of Anti-Drug Antibody (ADA) response, we investigated the role of the PEG molecule on the T-cell reactivity of certolizumab pegol (CZP), a pegylated anti-TNFα Fab. We generated T-cell lines raised against CZP and its non-pegylated form (CZNP) and demonstrated CZP primed few T-cells in comparison to CZNP. CZP-primed lines from 3 donors responded to a total of 5 epitopes, while CZNP-primed lines from 3 donors responded to a total of 7 epitopes, 4 epitopes were recognized by both CZP- and CZNP-primed lines. In line with this difference of T-cell reactivity, CZP is less internalized by the dendritic cells than CZNP. In vitro digestion assay of CZP by Cathepsin B showed a rapid removal of the PEG moiety, suggesting a limited influence of PEG on CZP proteolysis. We therefore demonstrate that pegylation diminishes antigen capture by dendritic cells, peptide presentation to T-cells and T-cell priming. This mechanism might reduce immunogenicity and contribute to the long half-life of CZP and possibly of other pegylated molecules. | |
| 34006137 | Evaluation of biomarkers related to zinc nutritional status, antioxidant activity and oxid | 2022 Jun | BACKGROUND: Oxidative stress (OS) is an important process related to the pathophysiology of rheumatoid arthritis and can be increased by the low intake of antioxidants. Zinc (Zn) is an important antioxidant trace-element for human health and the assessment of the nutritional status of this micronutrient in these patients is of relevance. AIM: This study aimed to evaluate Zn nutritional status in rheumatoid arthritis patients and its relation to OS. METHODS: A case-control study was carried out with 51 patients diagnosed with rheumatoid arthritis (RA group) recruited in Hospital São Paulo (São Paulo, Brazil) and 55 healthy women (CO group) from the campus of the University of São Paulo. Blood and 24-hour urine collection were used for biochemical parameters related to Zn status and OS. The assessment of dietary Zn was performed by three 24-hour dietary recalls. RESULTS: The RA group presented significative low Zn intake (p < 0.001) and plasma concentration (p = 0.040) of this mineral compared to the CO group. However, both groups were Zn deficient and the disease activity (DAS28 score) for RA patients did not influence Zn biomarkers. In addition, the antioxidant enzymes (superoxide dismutase and glutathione peroxidase) activity and the urinary 8-isoprostanes were reduced in RA patients. CONCLUSION: The evaluation of dietary intake and biochemical biomarkers indicates that rheumatoid arthritis patients are zinc deficient and have increased OS. | |
| 35126351 | The Expression of Inflammasomes NLRP1 and NLRP3, Toll-Like Receptors, and Vitamin D Recept | 2021 | Activated rheumatoid arthritis (RA) synovial fibroblasts (SFs) are among the most important cells promoting RA pathogenesis. They are considered active contributors to the initiation, progression, and perpetuation of the disease; therefore, early detection of RASF activation could advance contemporary diagnosis and adequate treatment of undifferentiated early inflammatory arthritis (EA). In this study, we investigated the expression of nucleotide-binding, oligomerization domain (NOD)-like receptor family, pyrin domain containing (NLRP)1, NLRP3 inflammasomes, Toll-like receptor (TLR)1, TLR2, TLR4, vitamin D receptor (VDR), and secretion of matrix metalloproteinases (MMPs) in SFs isolated from patients with RA, osteoarthritis (OA), EA, and control individuals (CN) after knee surgical intervention. C-reactive protein, general blood test, anticyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), and vitamin D (vitD) in patients' sera were performed. Cells were stimulated or not with 100 ng/ml tumor necrosis factor alpha (TNF-α) or/and 1 nM or/and 0.01 nM vitamin D3 for 72 h. The expression levels of NLRP1, NLRP3, TLR1, TLR2, TLR4, and VDR in all examined SFs were analyzed by quantitative real-time PCR (RT-qPCR). Additionally, the secretion of IL-1β by SFs and MMPs were determined by ELISA and Luminex technology. The expression of NLRP3 was correlated with the levels of CRP, RF, and anti-CCP, suggesting its implication in SF inflammatory activation. In the TNF-α-stimulated SFs, a significantly lower expression of NLRP3 and TLR4 was observed in the RA group, compared with the other tested forms of arthritis. Moreover, upregulation of NLRP3 expression by TNF-α alone or in combination with vitD3 was observed, further indicating involvement of NLRP3 in the inflammatory responses of SFs. Secretion of IL-1β was not detected in any sample, while TNF-α upregulated the levels of secreted MMP-1, MMP-7, MMP-8, MMP-12, and MMP-13 in all patient groups. Attenuating effects of vitD on the expression of NLRP3, TLR1, and TLR4 suggest potential protective effects of vitD on the inflammatory responses in SFs. However, longer studies may be needed to confirm or fully rule out the potential implication of vitD in SF activation in inflammatory arthritis. Both VDR and NLRP3 in the TNF-α-stimulated SFs negatively correlated with the age of patients, suggesting potential age-related changes in the local inflammatory responses. | |
| 35264509 | [Regression of diffuse large B-cell lymphoma after discontinuation of salazosulfapyridine] | 2022 | An 81-year-old man with a 3-year history of salazosulfapyridine (SASP) therapy for rheumatoid arthritis (RA) presented with pulmonary infiltrates and underwent computed tomography-guided biopsy. The histopathological and immunohistochemical evaluation confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL). He was recommended chemotherapy, which he refused. Due to the possibility of other iatrogenic immunodeficiency-associated lymphoproliferative disorders, SASP therapy was discontinued. SASP therapy withdrawal led to near-complete resolution of the lung infiltration shadows, and the serum soluble interleukin 2 receptor level returned to the normal range. This is the first report of a case of remission of DLBCL, following SASP therapy withdrawal in a patient with RA. | |
| 35603142 | The Association of Increase of Human T-Cell Leukemia Virus Type-1 (HTLV-1) Proviral Load ( | 2022 | OBJECTIVE: We evaluated changes of HTLV-1 proviral loads (PVLs) during treatment for rheumatoid arthritis (RA) and investigated whether these changes affect the clinical course in HTLV-1-positive RA patients. METHODS: A total of 41 HTLV-1-positive RA patients were analyzed. Their clinical picture including disease activity [Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR), DAS28-CRP, simplified disease activity index (SDAI), and clinical disease activity index (CDAI)] and comorbidity were evaluated over a 2-year period. PVLs from peripheral blood mononuclear cells were investigated by real-time polymerase chain reaction (PCR). We investigated whether HTLV-1 PVLs is altered, or which clinical characteristics affect changes of HTLV1-PVLs during 2-year treatment. RESULTS: Clinical disease activity was not changed during the 2-year observational period. The mean HTLV-1 PVL value change from baseline to 2 years was -1.2 copies/1000 PBMCs, which was not statistically significant. No baseline clinical characteristics influenced changes in HTLV-1 PVL. However, a numerical change of HTLV-1 PVLs was increased in 4 patients initiating the new biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) at 2-10 months after starting the new b/ts DMARDs (numerical increase was 24.87 copies/1000 PBMCs). Infection occurred in 4 patients, and 3 of those patients showed an increased HTLV-1 PVL. Univariate analysis revealed an association between increase of HTLV-1 PVL and incidence of infection. CONCLUSIONS: Over 2 years, HTLV-1 PVL did not significantly change in our HTLV-1-positive RA patients. Individual changes in HTLV-1 PVL were correlated with incidence of infection but not disease activity which indicate that we may take precaution toward infection at the uptick of HTLV-1 PVL in HTLV-1-positive RA patients. | |
| 35418125 | Construction of a two-dimensional artificial antioxidase for nanocatalytic rheumatoid arth | 2022 Apr 13 | Constructing nanomaterials mimicking the coordination environments of natural enzymes may achieve biomimetic catalysis. Here we construct a two-dimensional (2D) metal-organic framework (MOF) nanosheet catalyst as an artificial antioxidase for nanocatalytic rheumatoid arthritis treatment. The 2D MOF periodically assembles numbers of manganese porphyrin molecules, which has a metal coordination geometry analogous to those of two typical antioxidases, human mitochondrial manganese superoxide dismutase (Mn-SOD) and human erythrocyte catalase. The zinc atoms of the 2D MOF regulate the metal-centered redox potential of coordinated manganese porphyrin ligand, endowing the nanosheet with both SOD- and catalase-like activities. Cellular experiments show unique anti-inflammatory and pro-biomineralization performances of the 2D MOF, while in vivo animal model further demonstrates its desirable antiarthritic efficacy. It is expected that such a nanocatalytic antioxidation concept may provide feasible approaches to future anti-inflammatory treatments. |