Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 31824568 | Dissecting the Role of NF-κb Protein Family and Its Regulators in Rheumatoid Arthritis Us | 2019 | Rheumatoid arthritis (RA) is a chronic synovial autoinflammatory disease that destructs the cartilage and bone, leading to disability. The functional regulation of major immunity-related pathways like nuclear factor kappa B (NF-κB), which is involved in the chronic inflammatory reactions underlying the development of RA, remains to be explored. Therefore, this study has adopted statistical and knowledge-based systemic investigations (like gene correlation, semantic similarity, and topological parameters based on graph theory) to study the gene expression status of NF-κB protein family (NK(PF)) and its regulators in synovial tissues to trace the molecular pathways through which these regulators contribute to RA. A complex protein-protein interaction map (PPIM) of 2,742 genes and 37,032 interactions was constructed from differentially expressed genes (p ≤ 0.05). PPIM was further decomposed into a Regulator Allied Protein Interaction Network (RA(PIN)) based on the interaction between genes (5 NK(PF), 31 seeds, 131 hubs, and 652 bottlenecks). Pathway network analysis has shown the RA-specific disturbances in the functional connectivity between seed genes (RIPK1, ATG7, TLR4, TNFRSF1A, KPNA1, CFLAR, SNW1, FOSB, PARVA, CX3CL1, and TRPC6) and NK(PF) members (RELA, RELB, NFKB2, and REL). Interestingly, these genes are known for their involvement in inflammation and immune system (signaling by interleukins, cytokine signaling in immune system, NOD-like receptor signaling, MAPK signaling, Toll-like receptor signaling, and TNF signaling) pathways connected to RA. This study, for the first time, reports that SNW1, along with other NK regulatory genes, plays an important role in RA pathogenesis and might act as potential biomarker for RA. Additionally, these genes might play important roles in RA pathogenesis, as well as facilitate the development of effective targeted therapies. Our integrative data analysis and network-based methods could accelerate the identification of novel drug targets for RA from high-throughput genomic data. | |
| 31819587 | PtpA and PknG Proteins Secreted by Mycobacterium avium subsp. paratuberculosis are Recogni | 2019 | PURPOSE: Rheumatoid arthritis (RA) can result from complex interactions between the affected person's genetic background and environment. Viral and bacterial infections may play a pathogenetic role in RA through different mechanisms of action. We aimed to evaluate the presence of antibodies (Abs) directed against two proteins of Mycobacterium avium subsp. paratuberculosis (MAP) in sera of RA subjects, which are crucial for the survival of the pathogen within macrophages. Moreover, we analyzed the correlation of immune response to both proteins with the following homologous peptides: BOLF1(305-320), MAP_4027(18-32) and IRF5(424-434) to understand how the synergic role of Epstein-Barr virus (EBV) and MAP infection in genetically predisposed subjects may lead to a possible deregulation of interferon regulatory factor 5 (IRF5). MATERIALS AND METHODS: The presence of Abs against protein tyrosine phosphatase A (PtpA) and protein kinase G (PknG) in sera from Sardinian RA patients (n=84) and healthy volunteers (HCs, n=79) was tested by indirect ELISA. RESULTS: RA sera showed a remarkably high frequency of reactivity against PtpA in comparison to HCs (48.8% vs 7.6%; p<0.001) and lower but statistically significant responses towards PknG (27.4% vs 10.1%; p=0.0054). We found a significant linear correlation between the number of swollen joints and the concentrations of antibodies against PtpA (p=0.018). Furthermore, a significant bivariate correlation between PtpA and MAP MAP_4027(18-32) peptide has been found, suggesting that MAP infection may induce a secondary immune response through cross-reaction with IRF5 (R(2)=0.5). CONCLUSION: PtpA and PknG are strongly recognized in RA which supports the hypothesis that MAP infection may be involved in the pathogenesis of RA. | |
| 31741182 | Retrospective Analysis of the Impact of Adalimumab Initiation on Corticosteroid Utilizatio | 2020 Mar | INTRODUCTION: Treatment guidelines recommend low-dose corticosteroids as short-term therapy among rheumatoid arthritis (RA) patients. However, it may be difficult to wean/eliminate steroids once initiated. Initiation of more effective therapies such as biologics may help to taper corticosteroid use. The objective was to examine the impact of adalimumab (ADA) initiation on steroid utilization and non-drug medical costs among patients with RA. METHODS: A retrospective analysis was conducted among adult RA patients initiating ADA as the initial biologic in the MarketScan Database (2012-2016). Study outcomes included whether oral/injectable steroids were used, daily dose, dosage categories (< 5 and ≥ 5 mg/day), number of steroid injections, and non-drug medical costs. Outcomes were compared 6 months pre- and post-ADA initiation. Mixed effects logistic, classical linear, multinomial logistic models, and linear model with a log link and gamma distribution were used to adjust for patient demographic and health characteristics. RESULTS: The sample included 7404 ADA initiators. Compared to pre-ADA initiation, in the post-initiation period there was a reduction in proportions of patients using oral steroids (from 71.80 to 62.56%) and injectable steroids (from 34.91 to 29.88%), average daily dose of oral steroids (from 3.30 to 2.62 mg/day), patients with dose ≥ 5 mg/day (from 21.76 to 16.34%), number of injections (from 0.64 to 0.53), and non-drug medical costs (from $5356.30 to $5146.84) (P < 0.01). The multivariate analysis produced similar patterns. For example, post-ADA initiation, patients were less likely to use oral steroids [odds ratio (OR) 0.51; 95% confidence interval (CI) 0.47-0.56]; coefficient estimate for daily dose reduction was - 0.68 (95% CI - 0.81 to - 0.56); ratio estimate for medical costs was 0.91 (95% CI 0.86-0.97). CONCLUSIONS: Among patients with RA, following ADA initiation, there is a reduction in steroid utilization and dosage, and non-drug medical costs. Prospective studies should be conducted to confirm this relationship in the future. | |
| 31636721 | Indicator opportunistic infections after biological treatment in rheumatoid arthritis, 10 | 2019 | BACKGROUND: This research describes the incidence and factors associated with opportunistic infections in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: A retrospective longitudinal study was carried out from 2007 to 2018. We included RA patients treated with a tumor necrosis factor (TNF)-targeted bDMARD or non-TNF-targeted bDMARD from the start of bDMARDs. An independent variable was the development of an indicator of opportunistic infection after biological (IOIb) treatment. Secondary variables included sociodemographic, clinical, and treatments. We used survival techniques to estimate the incidence of IOIb, per 1000 patient-years (95% CI). We performed a Cox multivariate regression analysis model to compare the risk of IOIb. Results were expressed as a hazard ratio (HR). RESULTS: A total of 441 RA patients were included, that started 761 different courses of bDMARDs. A total of 81% were women with a mean age at first bDMARD of 57.3 ± 14 years. A total of 71.3% of the courses were TNF-targeted bDMARDs and 28.7% were non-TNF-targeted bDMARDs. There were 37 IOIb (25 viral, 6 fungal, 5 bacterial, 1 parasitic). Nine of these required hospitalization and one died. The global incidence of IOIb was 23.2 (16.8-32). TNF-targeted bDMARDs had 25 IOIb, incidence 20.5 (13.9-30.4), and non-TNF-targeted bDMARDs had 12 IOIb, incidence 31.7 (18-55.9). In the multivariate analysis, glucocorticosteroids (HR 2.17, p = 0.004) and lower lymphocyte count increased the risk for IOIb (HR 0.99, p = 0.005). CONCLUSIONS: The incidence of IOIb due to bDMARDs was 23 cases per 1000 patient-years. Close monitoring should be taken in the RA patients treated with bDMARDs and glucocorticosteroids, mainly in elderly patients and those with a low total lymphocyte count at the beginning of bDMARD treatment. | |
| 29277578 | Perceptions of patients with rheumatic diseases treated with subcutaneous biologicals on t | 2019 Nov | OBJECTIVE: To investigate, in Spanish patients with rheumatic diseases treated with subcutaneous biological drugs, their sources of information, which sources they consider most relevant, and their satisfaction with the information received in the hospital. METHODS: Rheumatologists from 50 hospitals handed out an anonymous survey to 20 consecutive patients with rheumatoid arthritis, axial spondyloarthritis or psoriatic arthritis treated with subcutaneous biologicals. The survey was developed ad hoc by 4 rheumatologists and 3 patients, and included questions with closed-ended responses on sources of information and satisfaction. RESULTS: The survey was handed-out to 1,000 patients, 592 of whom completed it (response rate: 59.2%). The rheumatologist was mentioned as the most important source of information (75%), followed by the primary care physician, nurses, and electronic resources; 45.2% received oral and written information about the biological, 46.1% oral only, and 6.0% written only; 8.7% stated that they had not been taught to inject the biological. The percentage of patients satisfied with the information received was high (87.2%), although the satisfaction was lower in relation to safety. If the information came from the rheumatologist, the satisfaction was higher (89.6%) than when coming from other sources (59.6%; P<.001). Satisfaction was also higher if the information was provided orally and written (92.8%) than if provided only orally (86.1%; P=.013); 45.2% reported having sought information from sources outside the hospital. CONCLUSIONS: The rheumatologist is key in transmitting satisfactory information on biological treatment to patients. He or she must also act as a guide, since a high percentage of patients seeks information in other different sources. | |
| 31853416 | Assessing spectral imaging of the human finger for detection of arthritis. | 2019 Dec 1 | Rheumatoid arthritis causes changes in the optical properties of tissues in the joints, which could be detected using spectral imaging. This has the potential for development of low cost, non-contact method for early detection of the disease. In this work, hyperspectral imaging system was used to obtain 24 images of proximal interphalangeal joints of 12 healthy volunteers. A large inter-subject variability was observed, but still an increase in transmittance in the spectral range of 600 nm - 950 nm could be associated to the joint in all images. The results of experiments were compared to detailed simulations of light propagation trough tissue. For the simulations, voxelized 3D models of unaffected and inflamed human joints with realistic tissue distributions were constructed from an in-vivo MRI scan of a healthy human finger. The simulated model of healthy finger successfully reproduced the experimental data, while the affected models indicated that the inflammation introduces detectable differences in the spectral and spatial features. The results were used to guide the design of a dedicated imaging system for detection of rheumatoid arthritis, that will be used in an upcoming clinical study. | |
| 31564293 | Treat to Target in Psoriatic Arthritis. | 2019 Nov | A treat-to-target approach to psoriatic arthritis has emerged as a topic of interest following successful application of this treatment paradigm to rheumatoid arthritis. In psoriatic arthritis, this has been examined in one randomized trial to date showing benefits of a tight control treatment strategy over standard care. Nonetheless, international treatment recommendations have called for clinicians to aim for a target of remission or low disease activity, although little or no consensus exists on how to measure these targets. An ideal measure to define a treatment target should be able to address all the disease domains and preferences pertinent to an individual patient. | |
| 30858896 | Effectiveness and safety of certolizumab pegol in rheumatoid arthritis patients in Canadia | 2019 | BACKGROUND: The aim of this study was to assess the real-world effectiveness and safety of certolizumab pegol (CZP) in rheumatoid arthritis (RA) patients, and the impact on patients' productivity, pain, and fatigue, in Canadian practice. METHODS: FαsT-CAN, a 2-year prospective, observational study, evaluated CZP use in Canadian adults with moderate to severe, active RA. The primary objective was to assess the proportion of patients achieving 28-joint Disease Activity Scores (DAS28) <2.6 at Week 104. Secondary and additional endpoints assessed the improvements in Patients' Assessment of Arthritis Pain (PtAAP), fatigue, Health Assessment Questionnaire-Disability Index (HAQ-DI), and the proportion of patients achieving minimal clinically important differences (MCID) in HAQ-DI. Validated arthritis-specific Work Productivity Surveys (WPS-RA) assessed the RA-associated impact on productivity. Incidence of CZP-related treatment-emergent adverse events (TEAEs) was reported for patients receiving ⩾1 dose of CZP (safety set). RESULTS: The full analysis set (baseline DAS28 ⩾ 2.6, ⩾1 dose of CZP and ⩾1 valid post-baseline DAS28 measurement) included 451 of the 546 patients recruited into the study; a total of 229/451 (50.8%) patients completed Week 104. At Week 104, 90/451 (20.0%) patients achieved DAS28 < 2.6. Rapid improvements in disease activity, pain, and fatigue were observed. At Week 104, 66.2% of patients achieved HAQ-DI MCID. Patients employed at Week 104, reported reduced absenteeism, and improved productivity. CZP-related TEAEs were consistent with the known CZP safety profile. CONCLUSIONS: CZP was an effective RA treatment in Canadian practice, and no new CZP-related safety signals were identified. The improvements in household and workplace productivity are the first observations in a real-world Canadian setting. | |
| 31914604 | A bispecific soluble receptor fusion protein that targets TNF-α and IL-21 for synergistic | 2020 Jan | This study was aimed at investigating the therapeutic effects of BITRAP, a bispecific fusion protein targeting TNF-α and IL-21, on the development of autoimmune arthritis in humans and mice. To verify the effects of BITRAP in human, peripheral blood mononuclear cells were cultured with BITRAP under IL-17-producing T (Th17) cell-polarizing conditions or osteoclast differentiation conditions. BITRAP treatment inhibited the production of IL-17 and vascular endothelial growth factor but increased the production of IL-10 in CD4(+) T cells, as well as directly suppressed osteoclastogenesis. Collagen-induced arthritis (CIA) and IL-1R antagonist (IL-1Ra) knockout mice were treated with BITRAP. Following injection in CIA mice, BITRAP rapidly migrated into the inflamed joints and remained there for 72 hours. Application of BITRAP attenuated the severity of autoimmune arthritis in CIA and IL-1Ra knockout mice by reducing the numbers of inflammatory cytokine-expressing cells and Th17 cells and antibody secretion. Finally, BITRAP suppressed STAT3 phosphorylation, as well as production of IL-17 and TNF-α, in murine splenic CD4(+) T cells. These findings suggest that BITRAP, a bispecific fusion protein targeting TNF-α and IL-21, may be an effective treatment to overcome the limitations of anti-TNF therapy for patients with rheumatoid arthritis. | |
| 31130713 | Infliximab Induced a Dissociated Response of Severe Periodontal Biomarkers in Rheumatoid A | 2019 May 26 | OBJECTIVE: Rheumatoid arthritis and periodontal disease are associated together, but the effect of therapy provided for one disease to the second one remained under-investigated. This study investigated effect of infliximab therapy used to treat rheumatoid arthritis (RA) on various biomarkers of periodontal disease (PD) severity including serologies of Porphyromonas gingivalis and Prevotella intermedia and matrix metalloproteinase 3. METHODS: Seventy nine RA patients were enrolled at the time to start infliximab therapy and the 28 joint disease activity score (DAS28), anti-cyclic citrullinated petides 2nd generation (anti-CCP2), anti-P. gingivalis antibody, and Matrix metalloproteinase 3 (MMP-3) were monitored before and at 6 months of infliximab therapy. Joint damage and severe periodontal disease were assessed at baseline. Anti-CCP2, anti-P. gingivalis antibody, and MMP-3 were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: At baseline, anti-CCP2 titers were associated with anti-P. gingivalis lipopolysaccharide (LPS)-specific antibodies titers (p < 0.05). Anti-P. gingivalis antibodies were not significantly correlated with clinical, biological, or destruction parameters of RA disease. At 6 months of infliximab therapy, MMP-3 level decreased (from 119 ± 103 ng/mL to 62.44 ± 52 ng/mL; p < 0.0001), whereas P. gingivalis antibody levels remained at the same level. DAS28 and inflammation markers C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR) also decreased significantly during infliximab therapy (p < 0.05) as anti-CCP2 levels (p < 0.001). Only high MMP-3 level at baseline was associated with infliximab efficacy (p < 0.01). CONCLUSION: MMP-3 level can be a useful marker of the efficacy of infliximab in RA patients. The treatment did not affect anti-P. gingivalis antibodies. | |
| 31168521 | Cost-effectiveness of different treat-to-target strategies in rheumatoid arthritis: result | 2019 | BACKGROUND: Adjusting medication of patients with rheumatoid arthritis (RA) until predefined disease activity targets are met, i.e. Treat-to-Target (T2T), is the currently recommended treatment approach. However, not much is known about long-term cost-effectiveness of different T2T strategies.We model the 5-year costs and effects of a step-up approach (MTX mono - > MTX + csDMARD combination - > Adalimumab - > second anti-TNF) and an initial combination therapy approach (MTX + csDMARD - > MTX + csDMARD higher dose - > anti-TNFs) from the healthcare and societal perspectives, by adapting a previously validated Markov model. METHODS: We constructed a Markov model in which 3-monthly transitions between DAS28-defined health states of remission (≤2.6), low (2.6 < DAS28 ≤ 3.2), moderate (3.2 < DAS28 ≤ 5.1), and high disease activity (DAS28 > 5.1) were simulated. Modelled patients proceeded to subsequent treatments in case of non-remission at each (3-month) cycle start. In case of remission for two consecutive cycles medication was tapered, until medication-free remission was achieved. Transition probabilities for individual treatment steps were estimated using data of Dutch Rheumatology Monitoring registry Remission Induction Cohort I (step-up) and II (initial combination). Expected costs, utility, and ICER after 5 years were compared between the two strategies. To account for parameter uncertainty, probabilistic sensitivity analysis was employed through Gamma, Normal, and Dirichlet distributions. All utilities, costs, and transition probabilities were replaced by fitted distributions. RESULTS: Over a 5-year timespan, initial combination therapy was less costly and more effective than step-up therapy. Initial combination therapy accrued €16,226.3 and 3.552 QALY vs €20,183.3 and 3.517 QALYs for step-up therapy. This resulted in a negative ICER, indicating that initial combination therapy was both less costly and more effective in terms of utility gained. This can be explained by higher (±5%) remission percentages in initial combination strategy at all time points. More patients in remission generates less healthcare and productivity loss costs and higher utility. Additionally, higher remission percentages caused less bDMARD use in the initial combination strategy, lowering overall costs. CONCLUSION: Initial combination therapy was found favourable over step-up therapy in the treatment of Rheumatoid Arthritis, when considering cost-effectiveness. Initial combination therapy resulted in more utility at a lower cost over 5 years. | |
| 30887278 | Vascular Arginase Is a Relevant Target to Improve Cerebrovascular Endothelial Dysfunction | 2020 Feb | Emerging data revealed that rheumatoid arthritis (RA) is associated with higher risk of cerebrovascular diseases. Whereas cerebral endothelial dysfunction is acknowledged as a critical aspect of cerebrovascular diseases, its presence in RA and the mechanisms involved are currently unknown. By using the model of rat adjuvant-induced arthritis (AIA), the present study investigated cerebrovascular reactivity in pressurized middle cerebral arteries (MCA) on day 33 post-immunization. The results revealed that arthritis induced a dramatic decrease in the vasodilatory response to acetylcholine (ACh), ADP, and bradykinin (n = 7-9 arteries, p < 0.0001). By using nor-NOHA, L-NAME, BH(4), and Tempol, the results showed that the reduced response to ACh relied on arginase overactivation (n = 8), low NOS activity (n = 8), BH(4) deficiency (n = 9), and excessive superoxide production (n = 9). Immunohistological analysis revealed an endothelial upregulation of arginase 2 (p < 0.05, n = 5-6) and NADPH oxidase (p < 0.05, n = 5-7) while eNOS expression was unchanged in AIA (n = 6). To assess whether arginase inhibition may be a relevant therapeutic, AIA rats were treated with an arginase inhibitor (nor-NOHA, 40 mg/kg/day, i.p., n = 20 rats) daily from day 10 to day 33 post-immunization. The treatment alleviated the impaired response of MCA to endothelium-dependent agonists, through an increase in NOS signaling and a suppression of BH(4) deficiency and superoxide overproduction. By contrast, it did not change the course of arthritis. In conclusion, arthritis induced a cerebrovascular endothelial dysfunction involving an imbalance in the arginase/NOS pathway. Arginase inhibition appears as a promising therapy beyond anti-rheumatic drugs for reducing the risk of cerebrovascular diseases in RA. | |
| 30831463 | Therapeutic effects of the total lignans from Vitex negundo seeds on collagen-induced arth | 2019 May | BACKGROUND: The seeds of Vitex negundo, with rich lignans metabolites, have been widely used as a traditional Chinese medicine and Ayurvedic herbal medicine for the treatment of rheumatism and joint inflammation. The total lignans of Vitex negundo seeds (TOV) were suggested to play an important role in the treatment of arthritis. PURPOSE: The aim of the study was designed to investigate the anti-arthritic effects of TOV on collagen-induced arthritis (CIA) in rats as well as its possible mechanisms. METHODS: TOV was prepared by combined macroporous resin and polyamide column chromatography, and constituents of TOV were analyzed by HPLC. CIA model in rats was established by immunization with chicken type II collagen and then the rats were intragastrically administrated with TOV for 30 days. Rat arthritis was evaluated by measurements of hind paw edema, arthritis index score, weight growth and indices of thymus and spleen, and by histological examination. Levels of serum MMP-2, MMP-3, MMP-9, IL-1β, IL-6, IL-8, IL-10, IL-17A and TNF-α were also examined. In addition, the expression of COX-2, iNOS and IκB, p-IκB in synovial tissues was evaluated by western blotting. The analgesic and anti-inflammatory effects of TOV were also evaluated in acetic acid-induced writhing and xylene-induced ear edema in mice, respectively. In addition, acute toxicity test was employed to preliminarily assess the safety of TOV. RESULTS: TOV significantly inhibited the paw edema and decreased the arthritis index, with no influence on the body weight and the indices of thymus and spleen of CIA rats. Meanwhile, TOV dose-dependently reduced the infiltration of inflammatory cells, synovial hyperplasia and attenuated cartilage damage. Additionally, the serum levels of IL-1β, IL-6, IL-8, IL-17A, TNF-α, MMP-3 and MMP-9 were markedly decreased, while the level of serum IL-10 was increased in TOV-treated rats. The significant reduction of the expression of COX-2, iNOS and p-IκB and the notable increase of IκB in synovial tissues were also observed in TOV-treated animals. TOV also significantly inhibited acetic acid-induced writhing and decreased xylene-induced ear edema in mice. Finally, the maximal tolerable dose (MTD) of TOV was determined to be 16.0 g/kg. CONCLUSION: These results suggest that TOV has significant anti-arthritic effects on collagen-induced arthritis in rats, which may be attributed to the inhibition of the levels of IL-1β, IL-6, IL-8, IL-17A, TNF-α, MMP-3 and MMP-9, and the increase of IL-10 in serum as well as down-regulation of the protein expression of COX-2 and iNOS in synovial tissues via suppressing the phosphorylation and degradation of IκB. Due to its high efficacy and safety, TOV can be regarded as a promising drug candidate for rheumatoid arthritis treatment. | |
| 31777792 | Blood Pressure Trends in Patients With Seropositive Rheumatoid Arthritis Compared With Con | 2019 May | OBJECTIVE: Rheumatoid arthritis (RA) conveys an increased risk of cardiovascular disease (CVD), making it imperative that traditional CVD risk factors are well controlled. This study compared blood pressure (BP) trends over 13 years among patients with seropositive RA and patients without RA who received care within a large health care system in Minnesota. METHODS: This retrospective cohort study compared 774 patients with seropositive RA and 3254 patients without RA who were matched on sex and year of birth (±5 years) and observed between 2005 and 2017. Generalized estimating equation models were used for longitudinal analyses, with adjustment for demographics, body mass index, smoking status, Charlson Comorbidity Index, number of BP measurements, and number of antihypertensive and oral glucocorticoid medications. RESULTS: Patients both with and without RA had a mean age of 55 and were predominately female (78% with RA; 79% without RA). The mean follow-up was 6.3 (SD 3.4) years for patients with RA and 7.2 (SD 3.3) years for patients without RA. Overall, systolic BP, diastolic BP, and the number of prescribed antihypertensive medications did not differ between groups. Patients with RA were more likely to be current smokers compared with patients without RA (23% vs 11%; P < 0.01) and were less likely to have serum lipid measurements (75% vs 85%; P < 0.01). CONCLUSION: BP was similarly controlled in patients with seropositive RA and patients without RA. However, diastolic BP in patients with RA was trending up in most recent years. Patients with RA were also more likely to smoke compared with controls and were less likely to have serum lipid measurements. | |
| 31713396 | [Progress of research on host immune responses induced by hookworm infection and its poten | 2019 Oct 10 | Hookworm infection remains a global health concern, which threatens human health. Hookworm infection is widely prevalent across the world, notably in tropical and subtropical areas. Recently, with the in-depth study of the immunity of parasitic infections, the"bidirectional effect"of host immune responses induced by helminth infections (including hookworm infections) has become increasingly prominent. On one hand, an immune response is induced in the host to kill the infected worms; on the other hand, the host produces a series of immunological changes that are conducive to the maintenance of parasite survival. The immune state of the host is regulated by various complicated mechanisms, and this may lead to the reduction in the incidence of allergic and autoimmune diseases or alleviation of the disease symptoms, which provide new insights into the management of these allergic and autoimmune diseases. The present article reviewed the advances of host immune responses induced by hook-worm infection and its potential values in the treatment of allergic asthma, inflammatory bowel disease and rheumatoid arthritis. | |
| 31698687 | The Regulation of Bone Metabolism and Disorders by Wnt Signaling. | 2019 Nov 6 | Wnt, a secreted glycoprotein, has an approximate molecular weight of 40 kDa, and it is a cytokine involved in various biological phenomena including ontogeny, morphogenesis, carcinogenesis, and maintenance of stem cells. The Wnt signaling pathway can be classified into two main pathways: canonical and non-canonical. Of these, the canonical Wnt signaling pathway promotes osteogenesis. Sclerostin produced by osteocytes is an inhibitor of this pathway, thereby inhibiting osteogenesis. Recently, osteoporosis treatment using an anti-sclerostin therapy has been introduced. In this review, the basics of Wnt signaling, its role in bone metabolism and its involvement in skeletal disorders have been covered. Furthermore, the clinical significance and future scopes of Wnt signaling in osteoporosis, osteoarthritis, rheumatoid arthritis and neoplasia are discussed. | |
| 31295952 | Th17 Cells and the IL-23/IL-17 Axis in the Pathogenesis of Periodontitis and Immune-Mediat | 2019 Jul 10 | Innate immunity represents the semi-specific first line of defense and provides the initial host response to tissue injury, trauma, and pathogens. Innate immunity activates the adaptive immunity, and both act highly regulated together to establish and maintain tissue homeostasis. Any dysregulation of this interaction can result in chronic inflammation and autoimmunity and is thought to be a major underlying cause in the initiation and progression of highly prevalent immune-mediated inflammatory diseases (IMIDs) such as psoriasis, rheumatoid arthritis, inflammatory bowel diseases among others, and periodontitis. Th1 and Th2 cells of the adaptive immune system are the major players in the pathogenesis of IMIDs. In addition, Th17 cells, their key cytokine IL-17, and IL-23 seem to play pivotal roles. This review aims to provide an overview of the current knowledge about the differentiation of Th17 cells and the role of the IL-17/IL-23 axis in the pathogenesis of IMIDs. Moreover, it aims to review the association of these IMIDs with periodontitis and briefly discusses the therapeutic potential of agents that modulate the IL-17/IL-23 axis. | |
| 31193412 | Interference of tumor necrosis factor inhibitor treatments on soluble tumor necrosis facto | 2019 Aug | OBJECTIVE: Soluble Tumor Necrosis Factor Receptor II (sTNFR2) is used as a biomarker to study cardiovascular disease (CVD) in diverse populations. TNF inhibitors (TNFi's) are a common treatment for inflammatory conditions. The objective of this study was to examine whether TNFi use impacts measured sTNFR2 levels. METHODS: We studied blood samples from a cohort of RA patients with clinical data and high sensitivity-C-reactive protein (hsCRP) measurements. To assess for interference, we tested the entire cohort for the expected positive correlation between sTNFR2 and TNFi using Pearson correlations. We then performed Pearson correlations between sTNFR2 and TNFi and sequentially removed subjects on adalimumab, etanercept, and infliximab; if interference was occurring, no correlation would be observed between hsCRP and sTNFR2, and correlation would be restored by removing subjects on the treatment causing the interference. RESULTS: We studied 190 subjects, 84.2% female, 73.4% anti-CCP positive. All subjects with sTNFR2 level exceeding measurable level were on etanercept. The expected positive correlation between hsCRP and sTNFR2 was not observed when assessing the entire cohort, r = 0.05, p = 0.51. However, the expected correlation was restored only after excluding subjects on etanercept, r = 0.46, p < 0.0001, and not adalimumab or infliximab. ELISA for sTNFR2 was performed using etanercept only and demonstrated direct binding to sTNFR2. CONCLUSIONS: Our data identified interference between etanercept and the TNFR2 assay. Of the TNFi's, only etanercept has a TNF-binding domain modeled after TNFR2. These data should be considered when designing studies using sTNFR2 in populations where etanercept is a treatment option. | |
| 31545276 | Guizhi-Shaoyao-Zhimu decoction possesses anti-arthritic effects on type II collagen-induce | 2019 Oct | BACKGROUND: Rheumatoid arthritis (RA) is a known intractable chronic inflammatory disease of synovial joints characterized by hyperplasia and consecutive inflammation with a high prevalence.Guizhi-Shaoyao-Zhimu (GSZD) is the first choice for clinical treatment of RA in Chinese traditional medicine. This study is aimed to explore the possible pharmacological mechanisms of anti-arthritic effect of GSZD. METHODS: Type II collagen-induced arthritis (CIA) rat model was used to study the anti-arthritic activity of GSZDin vivo, and toe swelling & arthritis score, serum levels of cytokines, and pathological examinations were carried out. In vitro, TNF-α induced MH7A cells were used to study the possible mechanisms of GSZD. The anti-proliferative effects of GSZD were determined by MMT assay, and pro-apoptotic activity of GSZD in MH7A cells was determined by flow cytometry analysis & DAPI staining. Furthermore, the adhesive and invasive abilities of MH7A cells were determined using cell adhesion and transwell assays. MMPs levels were determined by ELISA assays, and mRNA expressions of Caspase-3, -9, Bax, SOCS1, Bcl-2, JAK2, STAT-3 and -5 were determined using qRT-PCR analysis. Besides, the major chemical components in GSZD were analyzed by HPLC-QqQ-MS analysis. RESULTS: Our results showed GSZD reduced the toe swelling & arthritis score, and serum levels of TNF-α, IL-1β, IL-6 & IL-17a in CIA rats; pathological examination results indicated GSZD improved ankle joint injury in CIA rats.In vitro, GSZD showed significant anti-proliferative and pro-apoptotic effects on TNF-α stimulated MH7A cells. After GSZD treatment, the adhesive and invasive abilities of MH7A cells were reduced, and secretions of MMPs, IL-6 and IL-8 were also reduced. GSZD decreased the releases of TNF-α and IL-1β in LPS stimulated RAW 264.7 cells. Further studies showed GSZD up-regulated mRNA expressions of Caspase-3, -9, Bax, and SOCS1, whereas down-regulated mRNA expressions of Bcl-2, JAK2, STAT3 and STAT5. Besides, 13 major chemical components were identified in GSZD extracts through HPLC-QqQ-MS analysis. CONCLUSION: Our results suggested GSZD possesses an anti-rheumatic effect on CIA rats, and the possible mechanism is related to inhibiting inflammatory response, inhibiting invasion and migration of synovial fibroblasts, and inducing apoptosis in synovial fibroblasts. | |
| 31420237 | Development of a risk indicator score for the identification of interstitial lung disease | 2021 Apr | BACKGROUND: Clinically evident interstitial lung disease (ILD) affects 10%-42% of RA patients with prognostic implications. The aim of this study was to discern which factors are associated with the presence of ILD in RA patients and to develop a score that could help to stratify the risk of having ILD in RA patients. METHODS: Case-control study. We included RA patients recruited from ILD and rheumatology clinics. We retrieved the following data: gender, age, presence of extra articular manifestations, disease activity scores, antibodies status, ESR, and medication use. Multivariate logistic regression was performed. A risk indicator score was developed. RESULTS: Of 118 patients included in this study, 52 (44%) had RA-ILD (cases) and 66 (56%) had RA without ILD (controls). Twenty-six patients were male (22%), the mean age was 56.6±15.6 years. Five variables were significantly associated with the presence of ILD: male gender, smoking, extraarticular manifestations, a CDAI score>28, and ESR>80mm/h. The AUC of the final model curve was 0.86 (95%CI 0.79-0.92). Two potential cut-off points of the risk indicator score were chosen: a value of 2 points showed a sensitivity of 90.38% and a specificity of 63.64%, while a value of 4 points showed a sensitivity of 51.9% and a specificity of 90.9%. CONCLUSION: This study identified risk factors that could help identify which RA patients are at risk of having ILD through the development of a risk indicator score. This score needs to be validated in an independent cohort. |