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ID PMID Title PublicationDate abstract
33674349 Multi-cell type gene coexpression network analysis reveals coordinated interferon response 2021 Apr Systemic lupus erythematosus (SLE) is an incurable autoimmune disease disproportionately affecting women. A major obstacle in finding targeted therapies for SLE is its remarkable heterogeneity in clinical manifestations as well as in the involvement of distinct cell types. To identify cell-specific targets as well as cross-correlation relationships among expression programs of different cell types, we here analyze six major circulating immune cell types from SLE patient blood. Our results show that presence of an interferon response signature stratifies patients into two distinct groups (IFNneg vs. IFNpos). Comparing these two groups using differential gene expression and differential gene coexpression analysis, we prioritize a relatively small list of genes from classical monocytes including two known immune modulators: TNFSF13B/BAFF (target of belimumab, an approved therapeutic for SLE) and IL1RN (the basis of anakinra, a therapeutic for rheumatoid arthritis). We then develop a multi-cell type extension of the weighted gene coexpression network analysis (WGCNA) framework, termed mWGCNA. Applying mWGCNA to RNA-seq data from six sorted immune cell populations (15 SLE, 10 healthy donors), we identify a coexpression module with interferon-stimulated genes (ISGs) among all cell types and a cross-cell type correlation linking expression of specific T helper cell markers to B cell response as well as to TNFSF13B expression from myeloid cells, all of which in turn correlates with disease severity of IFNpos patients. Our results demonstrate the power of a hypothesis-free and data-driven approach to discover drug targets and to reveal novel cross-correlation across cell types in SLE with implications for other autoimmune diseases.
33605437 Investigation of immune complexes formed by mitochondrial antigens containing a new lipoyl 2021 Jun Primary biliary cholangitis (PBC) is characterized by the presence of serum anti-mitochondrial autoantibodies (AMAs). To date, four antigens among the 2-oxo-acid dehydrogenase complex family, which commonly have lipoyl domains as an epitope, have been identified as AMA-corresponding antigens (AMA-antigens). It has recently been reported that AMAs react more strongly with certain chemically modified mimics than with the native lipoyl domains in AMA-antigens. Moreover, high concentrations of circulating immune complexes (ICs) in PBC patients have been reported. However, the existence of ICs formed by AMAs and their antigens has not been reported to date. We hypothesized that AMAs and their antigens formed ICs in PBC sera, and analyzed sera of PBC and four autoimmune diseases (Sjögren's syndrome, systemic lupus erythematosus, systemic scleroderma, and rheumatoid arthritis) using immune complexome analysis, in which ICs are separated from serum and are identified by nano-liquid chromatography-tandem mass spectrometry. To correctly assign MS/MS spectra to peptide sequences, we used a protein-search algorithm that including lipoylation and certain xenobiotic modifications. We found three AMA-antigens, the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the E2 subunit of the 2-oxo-glutarate dehydrogenase complex (OGDC-E2) and dihydrolipoamide dehydrogenase binding protein (E3BP), by detecting peptides containing lipoylation and xenobiotic modifications from PBC sera. Although the lipoylated sites of these peptides were different from the well-known sites, abnormal lipoylation and xenobiotic modification may lead to production of AMAs and the formation ICs. Further investigation of the lipoylated sites, xenobiotic modifications, and IC formation will lead to deepen our understanding of PBC pathogenesis.
34971754 Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bu 2022 Mar OBJECTIVES: To reveal the heterogeneity of different cell types of osteoarthritis (OA) synovial tissues at a single-cell resolution, and determine by novel methodology whether bulk-RNA-seq data could be deconvoluted to create in silico scRNA-seq data for synovial tissue analyses. METHODS: OA scRNA-seq data (102,077 synoviocytes) were provided by 17 patients undergoing total knee arthroplasty; 9 tissues with matched scRNA-seq and bulk RNA-seq data were used to evaluate six in silico gene deconvolution tools. Predicted and observed cell types and proportions were compared to identify the best deconvolution tool for synovium. RESULTS: We identified seven distinct cell types in OA synovial tissues. Gene deconvolution identified three (of six) platforms as suitable for extrapolating cellular gene expression from bulk RNA-seq data. Using paired scRNA-seq and bulk RNA-seq data, an "arthritis" specific signature matrix was created and validated to have a significantly better predictive performance for synoviocytes than a default signature matrix. Use of the machine learning tool, Cell-type Identification By Estimating Relative Subsets of RNA Transcripts x (CIBERSORTx), to analyze rheumatoid arthritis (RA) and OA bulk RNA-seq data yielded proportions of T cells and fibroblasts that were similar to the gold standard observations from RA and OA scRNA-seq data, respectively. CONCLUSION: This novel study revealed heterogeneity of synovial cell types in OA and the feasibility of gene deconvolution for synovial tissue.
34843092 Patient-Reported Nausea and Fatigue Related to Methotrexate: A Prospective, Self-Controlle 2022 Feb INTRODUCTION: The magnitude and frequency of temporally related methotrexate (MTX)-associated side effects in rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients are difficult to quantify using traditional research methods. As proof of concept designed in part to implement digital data collection for remote patient monitoring, we conducted a study implementing self-controlled case series analytic methods to understand MTX-related symptoms in RA or PsA. METHODS: In study phase 1, adults with RA or PsA from the ArthritisPower(®) Registry (past or current oral MTX users) participated in a cross-sectional survey. In phase 2, current MTX users participated in a longitudinal study and completed the Patient-Reported Outcomes Measurement Information System (PROMIS(®)) 1-day nausea/vomiting and fatigue measure. Within-person change in PROMIS scores between risk (6-36 h post-dose) and control (96-144 h post-dose) windows were compared using mixed models. RESULTS: The baseline survey was completed by 671 participants (mean age: 54 years, 88% female, 92% white, 79% with RA). Among current MTX users (353/671 [53%]), most reported MTX-associated side effects (216/353 [61%]), most frequently fatigue (161/353 [46%]). Among phase 2 participants with (n = 39) and without (n = 84) baseline nausea, mean increase in PROMIS nausea was 5.1 units (P < 0.0001) and 0.7 units (P = 0.135), respectively; among those with (n = 51) and without (n = 72) baseline fatigue, mean increase in PROMIS fatigue was 3.9 units (P = 0.0003) and 0.4 units (P = 0.554), respectively. CONCLUSIONS: Digital remote patient monitoring presents an opportunity to detect and address medication tolerability in real time. Using a novel study design to control for between-person confounding, the magnitude of nausea and fatigue experienced by participants with RA and PsA temporally related to weekly MTX use was substantial.
34795765 Curcumin and Mesenchymal Stem Cells Ameliorate Ankle, Testis, and Ovary Deleterious Histol 2021 Rheumatoid arthritis (RA) is a chronic inflammatory condition, an autoimmune disease that affects the joints, and a multifactorial disease that results from interactions between environmental, genetic, and personal and lifestyle factors. This study was designed to assess the effects of curcumin, bone marrow-derived mesenchymal stem cells (BM-MSCs), and their coadministration on complete Freund's adjuvant- (CFA-) induced arthritis in male and female albino rats. Parameters including swelling of the joint, blood indices of pro-/antioxidant status, cytokines and histopathological examination of joints, and testis and ovary were investigated. RA was induced by a single dose of subcutaneous injection of 0.1 mL CFA into a footpad of the right hind leg of rats. Arthritic rats were treated with curcumin (100 mg/kg b.wt./day) by oral gavage for 21 days and/or treated with three weekly intravenous injections of BM-MSCs (1 × 10(6) cells/rat/week) in phosphate-buffered saline (PBS). The treatment with curcumin and BM-MSCs singly or together significantly (P < 0.05) improved the bioindicators of oxidative stress and nonenzymatic and enzymatic antioxidants in sera of female rats more than in those of males. Curcumin and BM-MSCs significantly (P < 0.05) improved the elevated TNF-α level and the lowered IL-10 level in the arthritic rats. Furthermore, joint, testis, and ovary histological changes were remarkably amended as a result of treatment with curcumin and BM-MSCs. Thus, it can be concluded that both curcumin and BM-MSCs could have antiarthritic efficacies as well as protective effects to the testes and ovaries which may be mediated via their anti-inflammatory and immunomodulatory potentials as well as oxidative stress modulatory effects.
34042308 Reply. 2021 Sep We appreciate the letter by Mortezavi et. al. describing vaccine response and the frequency of disease worsening in patients receiving tofacitinib. The ACR COVID Vaccine Guidance Task Force was aware of the two studies cited and appreciate their summary of the results. We would point out that in the rheumatoid arthritis study by Winthrop et. al., patients receiving tofacitinib in Study A had a lower likelihood of a satisfactory response to pneumococcal vaccination (45.1%) compared to placebo‐treated patients (68.4%), a difference of 23.3%, 95% CI −36.6 to −9.6%. The differences were numerically even larger for patients receiving concomitant tofacitinib and methotrexate (31.6% of patients with a satisfactory response, difference of −30.2%, 95% CI −47.3 to −11.4%) compared to methotrexate monotherapy.
33973415 Intermetatarsal bursitis, a novel feature of juxta-articular inflammation in early rheumat 2021 May 10 OBJECTIVE: Intermetatarsal bursae in the forefeet possess a synovial lining, similarly to joints and tendon-sheaths. Inflammation of these bursae (intermetatarsal bursitis; IMB) was recently identified as specific for early RA. We hypothesised that if IMB is indeed an RA-feature, then it associates with 1) other local inflammatory measures (synovitis/tenosynovitis/osteitis), 2) clinical signs and 3) responds to DMARD-therapy similarly as other local inflammatory measures. METHODS: 157 consecutive early RA-patients underwent unilateral contrast-enhanced 1.5T forefoot-MRI at diagnosis. MRIs were evaluated for IMB-presence, and for synovitis/tenosynovitis/osteitis in line with the RA MRI scoring-system (summed as RAMRIS-inflammation). MRIs at 4/12/24 months were evaluated for IMB-presence and -size in patients who had IMB at baseline and received early DMARD-therapy. Logistic regression and generalised estimating equations were used. ACPA-stratification was performed. RESULTS: 69% of RA-patients had ≥1 IMB. In multivariable analysis on bursa-level, presence of IMB was independently associated with local presence of synovitis and tenosynovitis (OR 1.69(95%CI 1.12-2.57) and 2.83(1.80-4.44), respectively), but not osteitis. On patient-level, IMB-presence was most strongly associated with tenosynovitis (2.92(1.62-5.24)). IMB-presence associated with local joint-swelling (2.7(1.3-5.3)) and tenderness (1.7(1.04-2.9)) independent of RAMRIS-inflammation. During treatment, IMB-size decreased between 0-12 months. This decrease associated with decrease in RAMRIS-inflammation; which was driven by synovitis-decrease. Within ACPA-positive and ACPA-negative RA similar results were obtained. CONCLUSION: IMB particularly accompanies inflammation of the synovial lining of joints and tendon-sheaths, showed a similar treatment response after DMARD-initiation and associates with typical clinical signs. These findings suggest that IMB represents a frequently present novel RA-feature of juxta-articular synovial inflammation.
33544720 SAveRUNNER: A network-based algorithm for drug repurposing and its application to COVID-19 2021 Feb The novelty of new human coronavirus COVID-19/SARS-CoV-2 and the lack of effective drugs and vaccines gave rise to a wide variety of strategies employed to fight this worldwide pandemic. Many of these strategies rely on the repositioning of existing drugs that could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we presented a new network-based algorithm for drug repositioning, called SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), which predicts drug-disease associations by quantifying the interplay between the drug targets and the disease-specific proteins in the human interactome via a novel network-based similarity measure that prioritizes associations between drugs and diseases locating in the same network neighborhoods. Specifically, we applied SAveRUNNER on a panel of 14 selected diseases with a consolidated knowledge about their disease-causing genes and that have been found to be related to COVID-19 for genetic similarity (i.e., SARS), comorbidity (e.g., cardiovascular diseases), or for their association to drugs tentatively repurposed to treat COVID-19 (e.g., malaria, HIV, rheumatoid arthritis). Focusing specifically on SARS subnetwork, we identified 282 repurposable drugs, including some the most rumored off-label drugs for COVID-19 treatments (e.g., chloroquine, hydroxychloroquine, tocilizumab, heparin), as well as a new combination therapy of 5 drugs (hydroxychloroquine, chloroquine, lopinavir, ritonavir, remdesivir), actually used in clinical practice. Furthermore, to maximize the efficiency of putative downstream validation experiments, we prioritized 24 potential anti-SARS-CoV repurposable drugs based on their network-based similarity values. These top-ranked drugs include ACE-inhibitors, monoclonal antibodies (e.g., anti-IFNγ, anti-TNFα, anti-IL12, anti-IL1β, anti-IL6), and thrombin inhibitors. Finally, our findings were in-silico validated by performing a gene set enrichment analysis, which confirmed that most of the network-predicted repurposable drugs may have a potential treatment effect against human coronavirus infections.
33058485 Management of Rheumatic Diseases During the COVID-19 Pandemic: A National Veterans Affairs 2021 Jul OBJECTIVE: To assess the experience, views, and opinions of rheumatology providers at Veterans Affairs (VA) facilities about rheumatic disease health care issues during the COVID-19 pandemic. METHODS: We performed an anonymized cross-sectional survey, conducted from April 16 to May 18, 2020, of VA rheumatology providers. We assessed provider perspectives on COVID-19 issues and resilience. RESULTS: Of the 153 eligible VA rheumatologists, 103 (67%) completed the survey. A significant proportion of providers reported a ≥50% increase related to COVID-19 in visits by telephone (53%), video-based VA video connect (VVC; 44%), and clinical video telehealth with a facilitator (29%). A majority of the responders were somewhat or very comfortable with technology for providing health care to established patients during the COVID-19 pandemic using telephone (87%), VVC (64%), and in-person visits (54%). A smaller proportion were comfortable with technology providing health care to new patients. At least 65% of rheumatologists considered telephone visits appropriate for established patients with gout, osteoporosis, polymyalgia rheumatica, stable rheumatoid arthritis, stable spondyloarthritis, or osteoarthritis; 32% reported a rheumatology medication shortage. Adjusted for age, sex, and ethnicity, high provider resilience was associated with significantly higher odds ratios (ORs) of comfort with technology for telephone (OR 3.1 [95% confidence interval (95% CI) 1.1-9.7]) and VVC visits for new patients (OR 4.7 [95% CI 1.4-15.7]). CONCLUSION: A better understanding of COVID-19 rheumatic disease health care issues using a health-system approach can better inform providers, improve provider satisfaction, and have positive effects on the care of veterans with rheumatic disease.
34386321 The influence of the gut microbiota on the bioavailability of oral drugs. 2021 Jul Due to its safety, convenience, low cost and good compliance, oral administration attracts lots of attention. However, the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract. One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs, influencing the drug transport process and altering some gastrointestinal properties. In this review, we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs, which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.
33802003 Functionalization of Polycaprolactone Electrospun Osteoplastic Scaffolds with Fluorapatite 2021 Mar 10 A capability for effective tissue reparation is a living requirement for all multicellular organisms. Bone exits as a precisely orchestrated balance of bioactivities of bone forming osteoblasts and bone resorbing osteoclasts. The main feature of osteoblasts is their capability to produce massive extracellular matrix enriched with calcium phosphate minerals. Hydroxyapatite and its composites represent the most common form of bone mineral providing mechanical strength and significant osteoinductive properties. Herein, hydroxyapatite and fluorapatite functionalized composite scaffolds based on electrospun polycaprolactone have been successfully fabricated. Physicochemical properties, biocompatibility and osteoinductivity of generated matrices have been validated. Both the hydroxyapatite and fluorapatite containing polycaprolactone composite scaffolds demonstrated good biocompatibility towards mesenchymal stem cells. Moreover, the presence of both hydroxyapatite and fluorapatite nanoparticles increased scaffolds' wettability. Furthermore, incorporation of fluorapatite nanoparticles enhanced the ability of the composite scaffolds to interact and support the mesenchymal stem cells attachment to their surfaces as compared to hydroxyapatite enriched composite scaffolds. The study of osteoinductive properties showed the capacity of fluorapatite and hydroxyapatite containing composite scaffolds to potentiate the stimulation of early stages of mesenchymal stem cells' osteoblast differentiation. Therefore, polycaprolactone based composite scaffolds functionalized with fluorapatite nanoparticles generates a promising platform for future bone tissue engineering applications.
33079445 Platelet Glycoprotein Ib α-Chain as a Putative Therapeutic Target for Juvenile Idiopathic 2021 Apr OBJECTIVE: To ascertain the role of platelet glycoprotein Ib α-chain (GPIbα) plasma protein levels in cardiovascular, autoimmune, and autoinflammatory diseases and whether its effects are mediated by platelet count. METHODS: We performed a two-sample Mendelian randomization (MR) study, using both a cis-acting protein quantitative trait locus (cis-pQTL) and trans-pQTL near the GP1BA and BRAP genes as instruments. To assess if platelet count mediated the effect, we then performed a two-step MR study. Putative associations (GPIbα/platelet count/disease) detected by MR analyses were subsequently assessed using multiple-trait colocalization analyses. RESULTS: After correction for multiple testing (Bonferroni-corrected threshold P ≤ 2 × 10(-3) ), GPIbα, instrumented by either cis-pQTL or trans-pQTL, was causally implicated with an increased risk of oligoarticular and rheumatoid factor (RF)-negative polyarticular juvenile idiopathic arthritis (JIA). These effects of GPIbα appeared to be mediated by platelet count and were supported by strong evidence of colocalization (probability of all 3 traits sharing a common causal variant ≥0.80). GPIbα instrumented by cis-pQTL did not appear to affect cardiovascular risk, although the GPIbα trans-pQTL was associated with an increased risk of cardiovascular diseases and autoimmune diseases but a decreased risk of autoinflammatory diseases, suggesting that this trans-acting instrument operates through other pathways. CONCLUSION: The role of platelets in thrombosis is well-established; however, our findings provide some novel genetic evidence that platelets may be causally implicated in the development of oligoarticular and RF-negative polyarticular JIA, and indicate that GPIbα may serve as a putative therapeutic target for these JIA subtypes.
33663677 [Remitting Seronegative Symmetrical Synovitis with Pitting Edema associated with Lung Mali 2021 Feb 28 Remitting seronegative symmetrical synovitis with pitting edema(RS3PE),the inflammatory arthritis attacking mainly elderly males,is characterized by symmetrical synovitis with pitting edema of the dorsum of hands and feet and the absence of rheumatoid factor.RS3PE commonly accompanies malignant tumor,infections and other diseases.Here we report a case of RS3PE associated with lung malignancy and review other six cases to summarize the clinical features,treatment and prognosis.
34875586 [Clinical evolution and levels of anti-S SARS-CoV-2 IgG in rheumatic disease and COVID-19] 2021 Controversies still exist regarding the humoral response to the virus SARS-CoV-2 in convalescent patients and seroconversion in patients with autoimmune diseases. There are few reports on the clinical and evolution of COVID-19 in the latter group. The objective was to examine the clinical and evolutionary characteristics associated with COVID-19 and the percentage of seroconversion in people with rheumatic diseases. Fifty-three patients were included, mainly with rheumatoid arthritis and lupus. The majority were female and average age 48 ± 14 years. Symptoms: fever (56%), anosmia (35.8%), dyspnea (34%), headache (30.2%) and cough (30.2%). Duration of infection 12 ± 7 days. Almost half of the patients were hospitalized (23, 43.4%), 5 in critical care units (9.4%) and 3 died (5.6%). The prevalence of steroid use was 56.6% (30), with an average dose of 8 mg/d, and 17 (32%) used immunosuppressive biopharmaceuticals. There was a correlation between age and the need for hospitalization with a risk of 9.4% per year. There were no differences with other variables. The presence in serum of IgG immunoglobulin against SARS-CoV-2 protein S was determined in 23/53 patients (43.4%), with detectable levels in 15 (62.2%), and in the 23 without autoimmune connective tissue diseases who suffered from COVID-19, 12 had detectable antibodies. Death in this group of rheumatic diseases was low, similar to the general population. More than half had specific antibodies against the virus regardless of the medication used.
34783147 Interleukin 38 serum level is increased in patients with vitiligo, correlated with disease 2021 Nov 15 BACKGROUND: Vitiligo is an acquired cutaneous depigmenting disease caused by a T helper (Th) 1-cytotoxic T cells driven autoimmune attack against melanocytes, in which Th17 is also involved. Interleukin (IL)-38 belongs to the IL-1 family of cytokines and suppresses Th1 and Th17 activation. IL-38 protein and mRNA levels have been found to be elevated in various autoimmune disorders and correlated with disease severity and activity, including psoriasis, systemic sclerosis, rheumatoid arthritis, and atopic dermatitis. No previous studies have been performed to investigate the expression of IL-38 in patients with vitiligo. AIM: To evaluate IL-38 serum level in patients with vitiligo compared to healthy controls (Hcs) and examine the association between IL-38 level and severity and activity of vitiligo. PATIENTS AND METHODS: The study comprised 21 patients with vitiligo and 21 Hcs. Vitiligo severity and activity were evaluated via Vitiligo Extent Score (VES) and Vitiligo Disease Activity (VIDA) Score, respectively. IL-38 serum level was evaluated by enzyme-linked immunosorbent assay. RESULTS: Vitiligo patients had significantly higher serum level of IL-38 than Hcs (p < 0.001). This level was significantly higher among patients with signs of vitiligo activity (p = 0.048), correlated positively with VES (p < 0.001), and correlated negatively with the age of patients (p = 0.001) and the age of disease onset (p = 0.022). CONCLUSION: IL-38 serum level was higher in patients with vitiligo than in Hcs and was related to vitiligo severity and signs of activity.
34761170 Browning of adipose tissue and increased thermogenesis induced by Methotrexate. 2021 Nov Methotrexate (MTX) is widely used for the treatment of rheumatoid arthritis due to its well-known anti-inflammatory role in immune cells but its impact on brown and beige adipose tissue biology has not yet been investigated. Here, we present the novel evidence that MTX treatment increases the gene expression of thermogenic genes in brown and beige adipose tissues in a fat cell autonomous manner. Furthermore, we show that treatment of mice with MTX is associated with cold resistance, improved glucose homeostasis, decreased inflammation, and reduced hepatosteatosis in high-fat diet states. Overall, our data provide novel evidence of a role of MTX on thermogenic tissues not previously appreciated.
34561395 Sleep problems in pain patients entering tertiary pain care: the role of pain-related anxi 2021 Sep 23 Chronic pain and sleep problems frequently co-occur. Pain itself disturbs sleep, but other factors may also contribute to sleep problems in pain patients. This cross-sectional study of 473 patients (69.9% female, mean age 47 years) entering tertiary pain management compared normally sleeping pain patients with those having recurring sleep problems to determine the relationship between pain and sleep. Groups were compared for pain and pain aetiology, pain-related anxiety, childhood adversities, use of sleep and pain medications, self-reported diseases, and sleep disorders. Furthermore, the association of pain-related anxiety (cognitive anxiety, escape/avoidance, fear, and physiological anxiety) with more disturbing sleep problems was investigated in the whole cohort. The main results were that those with sleep problems more often reported multiple health conditions than those sleeping normally (depression 31.6% vs 5.0%; angina pectoris 6.5% vs 0.0%; asthma 19.6% vs 1.7%; low back problems 55.1% vs 23.3%; joint disease other than rheumatoid arthritis 32.3% vs 18.3%). Accumulations of 5 or more childhood adversities were more often present in those with sleep problems. Restless legs symptoms were more common in those with sleep problems than those sleeping normally (33.2% vs 11.7%). Patients having sleep problems reported more use of sleep and pain medications than those sleeping normally. Findings about pain-related anxiety suggest physiological reactions as significant factors for increased sleep disturbances. These factors need to be addressed in the management of the comorbidity of pain and sleep problems, and research to understand mechanisms in these is sorely needed.
34451050 In Vitro Electrochemical Detection of Hydrogen Peroxide in Activated Macrophages via a Pla 2021 Aug 20 Oxidative stress, an excess of endogenous or exogenous reactive oxygen species (ROS) in the human body, is closely aligned with inflammatory responses. ROS such as hydrogen peroxide (H(2)O(2)), superoxide, and radical hydroxyl ions serve essential functions in fighting infection; however, chronic elevation of these species irreversibly damages cellular components. Given the central role of inflammation in a variety of diseases, including Alzheimer's disease and rheumatoid arthritis, a low-cost, extracellular, non-invasive assay of H(2)O(2) measurement is needed. This work reports the use of a platinum microelectrode array (Pt MEA)-based ceramic probe to detect time- and concentration-dependent variations in H(2)O(2) production by activated RAW 264.7 macrophages. First, these cells were activated by lipopolysaccharide (LPS) to induce oxidative stress. Chronoamperometry was then employed to detect the quantity of H(2)O(2) released by cells at various time intervals up to 48 h. The most stimulatory concentration of LPS was identified. Further experiments assessed the anti-inflammatory effect of dexamethasone (Dex), a commonly prescribed steroid medication. As expected, the probe detected significantly increased H(2)O(2) production by LPS-doped macrophages, subsequently diminishing the pro-inflammatory effect in LPS-doped cells treated with Dex. These results strongly support the use of this probe as a non-invasive, robust, point-of-care test of inflammation, with a high potential for multiplexing in further studies.
34442018 Cytomegalovirus-Associated Autoantibody against TAF9 Protein in Patients with Systemic Lup 2021 Aug 21 Background: Evidence indicates a causal link between cytomegalovirus (CMV) infection and the triggering of systemic lupus erythematosus (SLE). Animal studies have revealed that CMV phosphoprotein 65 (pp65) induces autoantibodies against nuclear materials and causes the autoantibody attack of glomeruli. IgG eluted from the glomeruli of CMVpp65-peptide-immunized mice exhibited cross-reactivity against dsDNA and TATA-box-binding protein associated factor 9 (TAF9). Whether the elevation of anti-TAF9 IgG is associated with anti-CMV reactivity in human lupus remains unclear. Methods: The sera from patients with rheumatic diseases, including ankylosing spondylitis (AS), gout, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren syndrome (SS) were examined using ELISA for antibodies of CMV, CMVpp65, and TAF9. Results: In total, 83.8% of the rheumatic patients had acquired CMV infections. The SLE patients had a high prevalence of anti-CMV IgM. The highest seropositivity rates for anti-HCMVpp65 and anti-TAF9 IgG were observed in the SLE patients. Purified anti-CMVpp65 IgG from CMVpp65/TAF9 dual-positive SLE sera reacted to both TAF9 and dsDNA. An increased prevalence of proteinuria and low hemoglobin levels were found in CMV IgG- and CMVpp65 IgG-positive SLE patients. Conclusions: This observation suggests that immunity to CMVpp65 is associated with cross-reactivity with TAF9 and dsDNA and that it is involved in the development of clinical manifestations in SLE.
34417338 Repetitive and forceful movements of the hand as predictors of treatment for pain in the d 2022 Jan OBJECTIVE: To investigate repetitive movements and the use of hand force as causes of treatment for distal upper extremities musculoskeletal disorders METHODS: A cohort of 202 747 workers in a pension health scheme from 2005 to 2017 in one of 17 jobs (eg, office work, carpentry, cleaning) was formed. Representative electro-goniometric measurements of wrist angular velocity as a measure for repetition and expert-rated use of hand force were used in a job exposure matrix (JEM). Job titles were retrieved from the Danish registers. Outcome was first treatment in the distal upper extremities. In a Poisson regression model, incidence rate ratios (IRRs) of treatment were adjusted for age, calendar-year, diagnosis of rheumatoid arthritis and arm fractures. In further analyses, wrist velocity or hand force was added. RESULTS: In men, wrist velocity had an IRR of 1.48 (95% CI 1.15 to 1.91) when the highest exposure level was compared with the lowest but with no clear exposure-response pattern. The effect became insignificant when adjusted for hand force. Hand force had an IRR of 2.65 (95% CI 2.13 to 3.29) for the highest versus the lowest exposure with an exposure-response pattern, which remained after adjustment for wrist velocity. Among women, no increased risk was found for hand force, while wrist velocity showed a significantly protective association with treatment. CONCLUSIONS: In men, occupational exposure to hand force more than doubled the risk of seeking treatment. The results for exposure to repetition were less clear. In women, we could not find any indications of an increased risk neither for force nor for repetition.