Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 29282305 | Antibody-Mediated Neutralization of uPA Proteolytic Function Reduces Disease Progression i | 2018 Feb 1 | Genetic absence of the urokinase-type plasminogen activator (uPA) reduces arthritis progression in the collagen-induced arthritis (CIA) mouse model to an extent just shy of disease abrogation, but this remarkable observation has not been translated into therapeutic intervention. Our aim was to test the potential in mice of an Ab that blocks the proteolytic capacity of uPA in the CIA model and the delayed-type hypersensitivity arthritis model. A second aim was to determine the cellular origins of uPA and the uPA receptor (uPAR) in joint tissue from patients with rheumatoid arthritis. A mAb that neutralizes mouse uPA significantly reduced arthritis progression in the CIA and delayed-type hypersensitivity arthritis models. In the CIA model, the impact of anti-uPA treatment was on par with the effect of blocking TNF-α by etanercept. A pharmacokinetics evaluation of the therapeutic Ab revealed target-mediated drug disposition consistent with a high turnover of endogenous uPA. The cellular expression patterns of uPA and uPAR were characterized by double immunofluorescence in the inflamed synovium from patients with rheumatoid arthritis and compared with synovium from healthy donors. The arthritic synovium showed expression of uPA and uPAR in neutrophils, macrophages, and a fraction of endothelial cells, whereas there was little or no expression in synovium from healthy donors. The data from animal models and human material provide preclinical proof-of-principle that validates uPA as a novel therapeutic target in rheumatic diseases. | |
| 29908722 | Ferulic acid, a dietary polyphenol suppresses osteoclast differentiation and bone erosion | 2018 Aug 15 | AIMS: Bone erosion induced by enhanced osteoclast formation is a debilitating pathological phenomenon in rheumatoid arthritis (RA). Recent finding has revealed that ferulic acid is associated with reduced osteoclast differentiation and bone erosion. However, the underlying mechanism through which ferulic acid inhibited osteoclast differentiation and bone erosion still remains to be elucidated. This study assessed the therapeutic effects of ferulic acid on osteoclast differentiation and bone erosion by targeting RANKL dependent NF-κB pathway. MAIN METHODS: RAW 264.7 monocyte/macrophage cells were left untreated/treated with 25, 50 and 100 μM ferulic acid prior to stimulation with/without RANKL and M-CSF. Osteoclast differentiation and formation was assessed by SEM and TRAP analysis whereas its functional activity of bone erosion was determined by pit formation assay. Crucial transcription factors (NF-κBp-65, NFATc1 and c-Fos) and osteoclast specific genes (TRAP, MMP-9 and Cathepsin K) were evaluated by quantitative RT-PCR. Further, the protein level expression of NF-κBp-65, NFAtc1, c-Fos and MMP-9 was assessed using western blot analysis. KEY FINDINGS: Our results demonstrated that ferulic acid significantly attenuated RANKL induced osteoclast differentiation as evidenced from SEM and TRAP staining analysis. A remarkable decrease in the bone resorption activity of osteoclasts was also noticed upon ferulic acid treatment. In addition, the down-regulation of RANKL induced NF-κB activation and its associated downstream factors like NFATc1, c-Fos, TRAP, Cathepsin K and MMP-9 was also observed upon ferulic acid treatment. SIGNIFICANCE: Thus, our findings evidence the anti-stimulatory and anti-resorptive role of ferulic acid via the inhibition of RANKL dependent NF-κB signalling pathway. | |
| 30198128 | Role of periodontal therapy in management of common complex systemic diseases and conditio | 2018 Oct | The goal of this review is to summarize the results of randomized trials reported since 2010 that assessed the effect of periodontal interventions on at least one systemic outcome in human subjects of any age, gender or ethnicity. Oral outcome measures included gingivitis, pocket depth, clinical attachment loss and/or radiographic bone loss and oral hygiene indices. Studies were excluded if the trial was not completed or if treatment was not randomized. The results suggest that nonsurgical periodontal intervention provided to pregnant women is safe and improves periodontal status without preventing adverse pregnancy outcomes. Nonsurgical periodontal intervention was also found to provide modest improvement in glycemic control in individuals with type 2 diabetes mellitus and periodontitis. Also, improving oral care through mechanical or chemical control of dental-plaque biofilm formation can contribute to the prevention of respiratory infections in differing clinical settings, including hospitals and nursing homes, and in patients with chronic obstructive pulmonary disease. No clinical trials were reported that tested the effect of periodontal interventions on medical outcomes of atherosclerosis, cardiovascular diseases, stroke, rheumatoid arthritis, Alzheimer's disease, chronic kidney disease or malignant neoplasia. | |
| 30476564 | Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with c | 2019 Feb | Collagen type II-induced arthritis (CIA) in Dark Agouti rats, a model of rheumatoid arthritis (RA), reproduces sexual dimorphism in the incidence and severity of the human disease. Th17 cells are central in the induction/propagation of autoimmune inflammation in CIA and RA. To assess mechanisms underlying this dimorphism in CIA rats, in lymph nodes draining inflamed joints and adjacent tissues (dLNs) from CIA rats of both sexes Th17/CD25+Foxp3+CD4+ T-regulatory cell (Treg) ratio, Th17 cell redifferentiation in functionally distinct subsets and Treg transdifferentiation into IL-17-producing cells (exTregs) were examined. In female rats (developing more severe CIA than their male counterparts) the higher frequency of all Th17 cells (reflecting partly their greater proliferation), followed by the higher frequency of highly pathogenic IFN-γ/GM-CSF-co-producing cells, but lower frequency of less pathogenic/immunoregulatory IL-10-producing cells among them was found. Additionally, compared with male rats, in female rats the lower frequency of Tregs was observed. Moreover, Tregs from female rats exhibited diminished proliferative and suppressive capacity (judging by PD-1 expression) and enhanced conversion into IL-17-producing cells. Given that TGF-β concentration was comparable in collagen-type II-stimulated dLN cell cultures from female and male rats, the shift in Th17/Treg ratio followed by augmented Th17 cell redifferentiation into IFN-γ/GM-CSF-co-producing cells and Treg transdifferentiation into IL-17-producing cells in female rats was associated with increased concentration of IL-6 in female rat dLN cell cultures, and the higher frequency of IL-1β- and IL-23-producing cells among their dLN cells. The lower frequency of IL-10-producing B cells, presumably B regulatory cells (Bregs) could also contribute to the shift in Th17/Treg ratio in female rat compared with male rat dLNs. Consistently, the lower expression of IL-35 (the cytokine promoting Treg expansion directly and indirectly, by favoring Breg expansion and conversion into IL-10/IL-35-producing cells) in female rat dLN cells was detected. Thus, the study identified putative cellular and molecular substrates of the sexual dimorphism in the immunopathogenesis and clinical outcome of CIA and suggested mechanisms to be targeted in females to improve control of Th17 response, and consequently clinical outcome of CIA, and possibly RA. | |
| 29367088 | Sinomenine inhibits fibroblast-like synoviocyte proliferation by regulating α7nAChR expre | 2018 Mar | Fibroblast like synoviocyte (FLS) is a crucial in the pathogenesis of rheumatoid arthritis (RA), and involved in inflammation and joint destruction. Sinomenine (SIN), an alkaloid derived from the plant Sinomenium acutum, has anti-inflammatory and analgesic effect and been used for RA treatment in China. Alpha 7 nicotinic acetylcholine receptors (α7nAChR), as the key receptor in cholinergic anti-inflammatory pathway (CAP) to inhibit inflammation, has been detected in RA patients synovium, but its role is still unclear. Here we investigated the association between the aggressive proliferation of FLS and α7nAChR expression and the effect of sinomenine. FLS was isolated from synovial tissues of adjuvant-induced-arthritis (AIA) rat. Tumor necrosis factor(TNF)-α was used to induce the aggressive proliferation of FLS. MTT assay was applied to evaluate the proliferation of FLS. The messenger RNA (mRNA) and protein levels of α7nAChR and early growth response gene-1 (Egr-1) were measured. The results showed that TNF-α induced FLS proliferation in vitro (P < .01) and increased the phosphorylation of ERK1/2 and the expression of Egr-1 and α7nAChR (P < .05 or P < .01). U0126, the inhibitor of ERK1/2 inhibited α7nAChR expression and FLS proliferation significantly (P < .05 or P < .01). Specific short interference RNA(siRNA) of α7nAChR decreased α7nAChR expression and inhibited FLS proliferation as well. SIN inhibited the proliferation of FLS and decreased the phosphorylation of ERK1/2, and the expression of Egr-1 and α7nAChR induced by TNF-α (P < .05). In conclusion, the expression of α7nAChR involved in the aggressive proliferation of FLS induced by TNF-α and was regulated by ERK/Egr-1 signal pathway. SIN inhibited FLS proliferation and α7nAChR expression through inhibiting ERK/Egr-1 signal pathway, this may contribute to the anti-inflammatory and anti-arthritic effect of SIN. | |
| 29119581 | Risk of tuberculosis comparison in new users of antitumour necrosis factor-α and with exi | 2018 Apr | WHAT IS KNOWN AND OBJECTIVE: Patients with rheumatic disease are at risk for infections. Evaluating antitumour necrosis factor (anti-TNF) drug-associated risk of infections requires justification of baseline risk in the population at high risk of infection. We examined the incidence of active tuberculosis (TB) and its risk factors in patients with rheumatic disease started with anti-TNF-α therapy or with existing disease-modifying antirheumatic drug (DMARD) therapy. METHODS: A retrospective cohort study of anti-TNF-α therapy new users (anti-TNF-α group) and those starting with a DMARD after the failure of at least one other DMARD or who had added to existing DMARD treatment (DMARD group) for rheumatic disease in the largest medical setting in Taiwan from 1 January 2005 through 31 November 2013 was conducted to determine relative risk of TB between patient groups. Patients in the DMARD group were stratified into "mild" and "severe" disease severity as proxies for low and high background risk of infection. RESULTS AND DISCUSSION: A total of 3640 patients were enrolled (anti-TNF: 955; DMARD: 2685). The incidence of TB was 903.9/100 000 patient-years for anti-TNF-α new users and 391.7/100 000 patient-years for DMARD switchers. In Cox regression model, adjusted HR for TB in the anti-TNF-α group was higher than for the entire DMARD group (aHR, 2.41; 95% confidence interval [CI], 1.2-4.85), subgroup with mild disease (2.91; 1.31-6.47) and subgroup with severe disease (1.65; 0.68-4.03). Significant independent risk factors for TB were being male, age ≥60 years, history of respiratory disease, glucocorticoids dose >7.5 mg/d and living in a TB-prevalent region. WHAT IS NEW AND CONCLUSION: Anti-TNF-α therapy was independently associated with increased risk of TB in patients with mild disease, but it was not significantly correlated in patients with severe disease after adjusting for confounders. | |
| 29150565 | The Role of Macrophages in the Response to TNF Inhibition in Experimental Arthritis. | 2018 Jan 1 | The reduction of synovial tissue macrophages is a reliable biomarker for clinical improvement in patients with rheumatoid arthritis (RA), and macrophages are reduced in synovial tissue shortly after initiation of TNF inhibitors. The mechanism for this initial response is unclear. These studies were performed to identify the mechanisms responsible for the initial reduction of macrophages following TNF inhibition, positing that efflux to draining lymph nodes was involved. RA synovial tissue and synovial fluid macrophages expressed CCR7, which was increased in control macrophages following incubation with TNF-α. Human TNF transgenic (hTNF-Tg) mice were treated with infliximab after development of arthritis. Ankles were harvested and examined by histology, immunohistochemistry, quantitative RT-PCR, ELISA, and flow cytometry. hTNF-Tg mice treated with infliximab demonstrated significant clinical and histologic improvement 3 d after the initiation of therapy, at which time Ly6C(+) macrophages were significantly reduced in the ankles. However, no evidence was identified to support a role of macrophage efflux to draining lymph nodes following treatment with infliximab. In contrast, apoptosis of Ly6C(+) macrophages in the ankles and popliteal lymph nodes, decreased migration of monocytes into the ankles, and a reduction of CCL2 were identified following the initiation of infliximab. These observations demonstrate that Ly6C(+) macrophage apoptosis and decreased ingress of circulating monocytes into the joint are responsible for the initial reduction of macrophages following infliximab treatment in hTNF-Tg mice. | |
| 29063464 | Diverse patterns of anti-TNF-α-induced lupus: case series and review of the literature. | 2018 Feb | The induction of autoantibodies is common following therapy with anti-TNF-α agents. However, anti-TNF-α-induced lupus (ATIL) is rare. We assessed the clinical characteristics of three patients with inflammatory bowel disease (IBD) who were treated with infliximab and developed distinct subsets of ATIL. Also, we searched for similar cases in the published literature. We describe three patients with ATIL. The first patient had a classical drug-induced lupus (DIL) presented by thrombocytopenia that resolved after infliximab discontinuation. The second case experienced symmetric polyarthritis of 14 joints in rheumatoid arthritis (RA)-like distribution accompanied by lymphopenia. The third one had a severe serositis including ascites and pleural and pericardial effusions along with pancytopenia. In this patient, ATIL coexisted with anti-TNF-α-induced hepatitis. The second and third patients met the American College of Rheumatology classification criteria for SLE. Nevertheless, all three cases exhibited ANA and anti-dsDNA positivity, and only the second patient had anticardiolipin (aCL IgG) and anti-histone antibodies. The coexistence of both lupus-like syndrome and hepatitis following anti-TNF-α therapy in the same patient is very rare, and to the best of our knowledge, only four such case reports are mentioned in literature. Patients with mild ATIL may tolerate another anti-TNF-α agent without recurrence of the disease. Rheumatologists should be aware of the distinct clinical presentations of ATIL and its coexistence with other rare anti-TNF-alpha complications such as hepatitis. | |
| 30569777 | Effects of Soluble Tumor Necrosis Factor (TNF) on Antibody-Dependent Cellular Cytotoxicity | 2019 Jul | Anti-TNF antibodies are major therapeutics for rheumatoid arthritis and have been approved for marketing in many countries. Antibody-dependent cellular cytotoxicity (ADCC) is considered to be a potential mechanism of action of anti-TNF antibodies, since some anti-TNF antibodies have been confirmed to induce cytotoxic effects on TNF-producing cells via ADCC and complement-dependent cytotoxicity (CDC) in in vitro experiments. In this study, we established a new stable effector cell line expressing human FcγRIIIa, CD16:KHYG-1, and compared the performance of this cell line with that of peripheral blood mononuclear cells (PBMCs) in ADCC assays against CHO-derived target cells expressing protease-sensitive pro-TNF. Although an inhibitory effect of soluble TNF released from pro-TNF expressing cells on ADCC activity was seen, clear dose-responsive ADCC activities were observed even in the presence or absence of TNF-α converting enzyme (TACE) inhibitor. However, significant differences in the ADCC activities in the presence or absence of TACE inhibitor were only noted when CD16:KHYG-1 cells were used as the effector cells. Our findings indicate that soluble TNF may influence ADCC activity of anti-TNF antibody. Moreover, the fact that the influence was able to be detected only in the case using stable effector cell also suggests that the stable effector cell established this time enable highly accurate ADCC measurement. | |
| 29717163 | In-patient outcomes of Hematopoietic Stem Cell Transplantation in Patients with Immune Med | 2018 May 1 | The impact of underlying immune-mediated inflammatory diseases (IMID) in patients undergoing hematopoietic stem cell transplant (HSCT) is unclear. Hematopoietic cell transplantation co-morbidity index (HCT-CI) is gaining acceptance as a reliable clinical method to score pre-transplant co-morbidities. Higher HCT-CI from a co-morbid IMID implies higher NRM. However, HCT-CI integrates many IMIDs with different pathogenesis and treatment together which may lead to spurious results. We performed a cross-sectional study using Nationwide Inpatient Sample dataset from 1998 to 2011 to compare the outcomes of HSCT in patients with different co-morbid IMIDs with patients without any co-morbid IMIDs. In both our multivariate and stringent matched-pair analysis, ulcerative colitis (UC) was associated with increased mortality while rheumatoid arthritis and psoriasis were associated with lower mortality as compared to no IMID group. Furthermore, in allogeneic HSCT subgroup, UC was associated with higher mortality and psoriasis was associated with lower mortality. In conclusion, we found that depending on the type of HSCT, each IMID has a different impact on outcomes of HSCT. Furthermore, UC patients had increased mortality if they had primary sclerosing cholangitis and had a higher risk of opportunistic infections like tuberculosis and cytomegalovirus suggesting the need for increased vigilance in this cohort. | |
| 30103041 | Clinical and immunological parameters of Sjögren's syndrome. | 2018 Oct | Sjögren's syndrome (SS) is a chronic autoimmune disease that primarily affects the exocrine glands, resulting in their functional impairment. In SS, lymphocytic infiltration of salivary and lacrimal glands, and deposition of several types of autoantibodies, mainly anti-SS-A (anti-Ro) and anti-SS-B (anti-La), lead to chronic inflammation, with xerostomia and keratoconjunctivitis sicca. In its primary form (pSS), SS does not involve additional connective tissue diseases, whereas in its secondary and more common form (sSS), SS presents in association with other rheumatic autoimmune diseases, mainly rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). As in most autoimmune diseases, environmental, hormonal and genetic factors are implicated in SS pathogenesis. In SS T cells predominate in mild lesions, whereas B cells predominate in advanced lesions. Th1, Th2, Th17, follicular helper T (Tfh) cells and regulatory cells (Tregs/Bregs), with their characteristic cytokine profiles, have been implicated in the pathogenesis of SS. It has been suggested that Th1 and Th17 cells initiate SS and, as the disease progresses, Th2 and Tfh cells predominate. It is assumed that, as in all autoimmune and inflammatory conditions, tolerance defects contribute to SS pathogenesis. It is intriguing that in SS it remains unclear which types of regulatory cells are functional and whether they ameliorate or worsen the disease. In this review we present a comprehensive update on SS with emphasis on immune system involvement, and suggest new insights into SS immunopathogenesis. | |
| 28927315 | Systematic review and meta-analysis of the epidemiology of polyautoimmunity in Sjögren's | 2018 Mar | OBJECTIVE: The epidemiology of polyautoimmunity in Sjögren's syndrome (secondary Sjögren's syndrome - sSS) is not well defined and has not been investigated before using a systematic approach. We conducted a systematic review of the epidemiology of sSS associated with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), scleroderma, and myositis, assessing the prevalence rates (PRs) and clinical and serological features of sSS. METHOD: A systematic literature search of PubMed and Embase databases (updated to March 2016) was performed to identify all published data on PR, demographic proï¬le, clinical manifestations, laboratory features, and causes of death associated with sSS. The PR's of sSS were summarized with PRs and 95% confidence intervals (CIs). RESULTS: The literature search identified 1639 citations, of which 42 fulfilled the inclusion criteria. Only 19 studies were of moderate to good quality and were selected for the meta-analysis. According to a random-effects model, the pooled PR for sSS associated with RA was 19.5% (95% CI 11.2 to 27.8) and the pooled PR for sSS associated with SLE was 13.96% (95% CI 8.88 to 19.04). The female/male ratio of sSS in the RA population was 14.7 (95% CI 7.09 to 256) and in the SLE population was 16.82 (95% CI 1.22 to 32.4). CONCLUSION: Prevalence rates of sSS vary widely in different populations. Both meta-analyses conducted in the RA and SLE populations were characterized by a high degree of study heterogeneity. The results of this meta-analysis highlight the need for better quality population studies. | |
| 30701854 | Correlations between indicators of interleukin-10 and interleukin-6 in patients with perio | 2018 Apr 19 | AIM: Determination of the concentration of interleukin-10 (IL-10) and interleukin-6 (IL-6) in serum of patients with periodic disease (PD) before and after treatment with colchicin, as well as the identification of correlation between the indicators of these parameters. MATERIALS AND METHODS: We examined 188 patients with PD (89 men, 99 women) aged from 12 to 69 years, as well as 44 patients with rheumatoid arthritis (RA) as a comparison group and 41 healthy people of the control group. Patients were divided into groups: 1 - PD colchicinotherapy patients with seizures without amyloidosis that do not respond to treatment maximum dose of colchicine 2.0 mg/day; 2nd-PD patients without amyloidosis, not responding to treatment 1.5 mg/day colchicine; 3rd - PD patients that responds to certain doses of colchicine (0.5 to 2.0 mg/day); 4th - PD patients without amyloidosis who did not receive treatment; 5-I of the healthy persons of the control group; 6-I - RA patients. The concentration of IL-10 in blood serum was determined by enzyme immunoassay ELISA, and IL-6 - immunochemiluminescent method. For statistical processing the computer program SPSS is used. The results were considered statistically significant at the level of reliability p<0.05. RESULTS: The results of the studies showed the same nature of changes in IL-10 production in different groups of patients. Statistically significant positive correlation of elevated serum concentrations of IL-6 and IL-10 (p<0.05) was found in patients with PD of all groups, as well as in patients with RA. CONCLUSION: In patients with PD (both colchicin-resistant and colchicin-sensitive) increased serum concentration of IL-10 was accompanied by an increased level of IL-6 in serum. Changes in the level of IL-10 in PD have a certain prognostic and pathogenetic significance and lead to the development of "persistent, sluggish" inflammatory process in the extracurricular period of PD in both colchicin-resistant and other groups of patients with PD. | |
| 29386006 | The MRZ reaction helps to distinguish rheumatologic disorders with central nervous involve | 2018 Jan 31 | BACKGROUND: Some rheumatologic disorders may initially manifest with central nervous system (CNS) affection, mimicking the clinical, magnetic resonance imaging, and cerebrospinal fluid findings of multiple sclerosis (MS). The MRZ reaction (MRZR), composed of the three respective antibody indices (AIs) against measles, rubella, and varicella zoster virus, has been found positive frequently in MS patients. However, it is unclear whether the MRZR is helpful to distinguish rheumatologic disorders with CNS involvement (RDwCNS) from MS. METHODS: The MRZR was evaluated in patients with RDwCNS (n = 23), MS (n = 46; age and sex matched to patients with RDwCNS), and other inflammatory autoimmune neurological diseases affecting the CNS (OIND; n = 48). Both the stringency levels that have been used in previous MRZR studies, MRZR-1 (≥ 1 of 3 AIs positive) and MRZR-2 (≥ 2 of 3 AIs positive), were applied. RESULTS: There was no statistically significant difference in the prevalence of positive MRZR between patients with RDwCNS (MRZR-1: 13.0% and MRZR-2: 8.7%, respectively) and OIND (MRZR-1: 22.9% and MRZR-2: 8.3%, respectively). Compared to these two study cohorts, the MS group exhibited significantly higher prevalences of positive MRZR (MRZR-1: 82.6%, MRZR-2: 63.0%; p < 0.005 each). CONCLUSIONS: Considering the high specificity of MRZR-2 for MS found in this study, MRZR-2 can be a useful diagnostic tool for distinguishing MS from RDwCNS or OIND. | |
| 29335340 | Anticitrullinated Protein Antibodies Induce Inflammatory Gene Expression Profile in Periph | 2018 Mar | OBJECTIVE: Anticitrullinated protein antibodies (ACPA) have major diagnostic significance in rheumatoid arthritis (RA). ACPA are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. The presence of ACPA is associated with joint damage and extraarticular manifestations, suggesting that ACPA may have a significant role in the pathogenesis of RA. METHODS: To verify the effect of ACPA on RA-immune cells, peripheral blood mononuclear cells (PBMC) from cyclic citrullinated peptide (CCP)-positive patients with RA and healthy controls were cocultured in vitro with ACPA. ACPA-positive stained cells were analyzed by flow cytometry and the effect of ACPA on mRNA expression levels was evaluated by real-time PCR. We tested whether the stimulatory effects induced by ACPA could be inhibited by the addition of a new multiepitope citrullinated peptide (Cit-ME). RESULTS: We found that ACPA bind specifically to PBMC from CCP-positive patients with RA through the Fab portion. ACPA induce upregulation of pathogenic cytokine expression (4- to 13-fold increase) in PBMC derived from CCP-positive patients with RA. Moreover, ACPA upregulated IL-1β and IL-6 mRNA expression levels by 10- and 6-fold, respectively, compared to control IgG. Cit-ME, a genuine ligand of ACPA, inhibited the ACPA-induced upregulation of IL-1β and IL-6 by 30%. CONCLUSION: ACPA bind to a limited percentage of PBMC and upregulate inflammatory cytokine expression, suggesting that ACPA is involved in RA pathogenesis. Targeting ACPA to decrease their pathogenic effects might provide a novel direction in developing therapeutic strategies for RA. | |
| 29431292 | Chikungunya: A rheumatologist's perspective. | 2018 Mar | Chikungunya (CHIK), a viral infection, is transmitted by Aedes mosquitoes. It is characterized by a phase of acute infection, which is sometimes followed by chronic rheumatisim in the form of arthralgia or myalgia that can last for months and even years. Several studies have been conducted to understand the mechanisms underlying inflammation associated with CHIK infection, persistence of viruses in monocytes-macrophages, and their relationship to the chronic symptoms. Chronic arthritis is one of the serious complications of CHIK infection, which is characterized by swelling and acute pain that poorly responds to treatment with analgesics. Such debilitating chronic joint pain mimics that of rheumatic arthritis and significantly compromises the quality of life. Diagnosis is primarily based on the initial viral detection using molecular methods or the use of virus culture, and on the basis of an immune response in the later stages. In the absence of published guidelines, physicians are often limited to prescribing analgesics and steroids for symptomatic care, as there is no accurate approach for the treatment and management of pain. This review aims to focus on the need for appropriate guidelines that will aid in developing suitable pharmacologic treatment to manage pain associated with post-CHIK chronic inflammatory rheumatism. | |
| 30396903 | To switch or not to switch: results of a nationwide guideline of mandatory switching from | 2019 Feb | OBJECTIVES: Real-world evidence on effectiveness of switching to biosimila r etanercept is scarce. In Denmark, a nationwide guideline of mandatory switch from 50 mg originator (ETA) to biosimilar (SB4) etanercept was issued for patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA) in 2016. Clinical characteristics and treatment outcomes were studied in ETA-treated patients, who switched to SB4 (switchers) or maintained ETA (non-switchers). Retention rates were compared with that of a historic cohort of ETA-treated patients. Switchers who resumed ETA treatment (back-switchers) were characterised. METHODS: Observational cohort study based on the DANBIO registry. Treatment retention was explored by Kaplan-Meier plots and Cox regression (crude, adjusted). RESULTS: 1621 (79%) of 2061 ETA-treated patients switched to SB4. Disease activity was unchanged 3 months' preswitch/postswitch. Non-switchers often received 25 mg ETA (ETA 25 mg pens/syringes and powder solution were still available). One-year adjusted retention rates were: non-switchers: 77% (95% CI: 72% to 82%)/switchers: 83% (79% to 87%)/historic cohort: 90% (88% to 92%). Patients not in remission had lower retention rates than patients in remission, both in switchers (crude HR 1.7 (1.3 to 2.2)) and non-switchers (2.4 (1.7 to 3.6)). During follow-up, 120 patients (7% of switchers) back-switched to ETA. Back-switchers' clinical characteristics were similar to switchers, and reasons for SB4 withdrawal were mainly subjective. CONCLUSION: Seventy-nine per cent of patients switched from ETA to SB4. After 1 year, adjusted treatment retention rates were lower in switchers versus the historic ETA cohort, but higher than in non-switchers. Withdrawal was more common in patients not in remission. The results suggest that switch outcomes in routine care are affected by patient-related factors and non-specific drug effects. | |
| 30599891 | Anti-arthritic and anti-inflammatory effects of (-)-Epicatechin-3-O-β-d-allopyranoside, a | 2019 Jan | BACKGROUND: (-)-Epicatechin-3-O-β-d-allopyranoside (ECAP) is isolated from the popular Chinese herbal medicine Davallia formosana, which has been used to treat bone diseases including bone fracture, arthritis, and osteoporosis. PURPOSE: To investigate the antiarthritic and the anti-inflammatory effect of ECAP on a mouse model of collagen-induced arthritis (CIA) and in vitro. METHODS: Male DBA/1 J mice were immunized by administering an intradermal injection of 100 µg of type II collagen in Freund's complete adjuvant. The control groups (vehicle) and ECAP were administered orally at doses of 1 ml/kg (H(2)O), 50 and 100 mg/ml/kg once a day from Day 22 to Day 42 after primary immunization. Paw swelling, arthritis severity score, and histological changes were examined. Enzyme-linked immunosorbent assay was used to measure the levels of cytokines, including tumor necrosis factor alpha (TNF-α), interleukin (IL)-10, IL-17, IL-4, and interferon-γ (IFN-γ), in splenocytes. Furthermore, the anti-inflammatory activities of ECAP were investigated in vitro by measuring nitric oxide (NO) levels in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. RESULTS: In the CIA model, the oral administration of ECAP ameliorated paw edema and reduced the arthritis severity score and disease incidence. Histopathological examination demonstrated that ECAP treatment effectively protected the bone and cartilage of knee joints from erosion, lesion formation, and deformation compared with the vehicle treatment. ECAP also reduced IL-1β and MMP-9 expression in inflamed joints. Compared with the vehicle-treated mice with CIA, the reduced severity of the disease in ECAP-treated mice was associated with decreased levels of TNF-α and IL-17 and increased levels of IL-10 and IL-4 in the supernatants of splenocyte cultures. Flow cytometry analysis demonstrated that ECAP increased the population of CD4(+)CD25(+) regulatory T cells, thereby inhibiting the B cell population. Anticollagen IgG1 and IgG2a levels decreased in the serum of ECAP-treated mice. ECAP suppressed LPS-induced NO production in RAW264.7 macrophages. CONCLUSION: The administration of ECAP effectively suppressed inflammation and inflammatory pain and adjuvant-induced arthritis, indicating its therapeutic potential in the treatment of rheumatoid arthritis. | |
| 29512823 | Variable domain N-linked glycosylation and negative surface charge are key features of mon | 2018 Jun | Autoreactive B cells have a central role in the pathogenesis of rheumatoid arthritis (RA), and recent findings have proposed that anti-citrullinated protein autoantibodies (ACPA) may be directly pathogenic. Herein, we demonstrate the frequency of variable-region glycosylation in single-cell cloned mAbs. A total of 14 ACPA mAbs were evaluated for predicted N-linked glycosylation motifs in silico, and compared to 452 highly-mutated mAbs from RA patients and controls. Variable region N-linked motifs (N-X-S/T) were strikingly prevalent within ACPA (100%) compared to somatically hypermutated (SHM) RA bone marrow plasma cells (21%), and synovial plasma cells from seropositive (39%) and seronegative RA (7%). When normalized for SHM, ACPA still had significantly higher frequency of N-linked motifs compared to all studied mAbs including highly mutated HIV broadly-neutralizing and malaria-associated mAbs. The Fab glycans of ACPA-mAbs were highly sialylated, contributed to altered charge, but did not influence antigen binding. The analysis revealed evidence of unusual B-cell selection pressure and SHM-mediated decrease in surface charge and isoelectric point in ACPA. It is still unknown how these distinct features of anti-citrulline immunity may have an impact on pathogenesis. However, it is evident that they offer selective advantages for ACPA(+) B cells, possibly through non-antigen driven mechanisms. | |
| 29770589 | Short-term Follow-up of Antibiotic-loaded Articulating Cement Spacers in Two-stage Revisio | 2018 May | OBJECTIVE: Infection of total knee arthroplasty (TKA) is a rare but devastating complication. Two-stage revision is an effective treatment for late infected TKA. This study aimed to assess the short-term results of two-stage revision using articulating antibiotic-loaded spacers. METHODS: Twenty-five patients (10 men and 15 women) were diagnosed with late infections after TKA and treated with two-stage revision from April 2006 to August 2010; 19 of these patients had TKA for osteoarthritis and 6 for rheumatoid arthritis. Median age was 64.9 (range, 56-83) years. In the first-stage surgery, the prosthesis and all bone cement was removed. After thorough debridement, bone cement with vancomycin and tobramycin was put into a die cavity and made into temporary femoral and tibial spacers, respectively. In the cases of good knee range of motion, the temporary spacers were affixed to the bone surface using the same antibiotic bone cement. In the second surgery, gentamycin Refobacin Bone Cement with vancomycin was used to fix the prosthesis. After two-stage revision, patients were followed up clinically and radiologically at 1, 3, and 6 months, and then annually. Knee Society Score (KSS), knee function score, knee pain score, and knee range of motion (ROM) were assessed. RESULTS: Among the group, all spacers were easily removed, and bone defect degree showed no obvious change compared with pre-implant, 24 (96%) patients had been debrided once, and 1 patient had been debrided twice before reimplant prosthesis. Mean follow-up was 64.2 (range, 52-89) months. There was no infection recurrence at final follow-up. Compared with preoperative data, the KSS (66 [59, 71], 83 [80, 88] vs 46 [43, 57], P < 0.01), knee function score (43 [42, 49], 78 [73, 82] vs 32 [25, 37], P < 0.01), knee pain score (34 [33, 37], 42 [40, 45] vs 18 [16, 23], P < 0.01), and knee ROM (92° [86°, 96°], 94° [90°, 98°] vs 78° [67°, 86°], P < 0.01) were all improved during follow-up and at final visit. Three patients experienced complications in the interval period: one case had knee dislocation, one had knee instability, and one had a chip in the femoral component of the spacer. CONCLUSION: Using articulating antibiotic-loaded spacers showed benefits for treating infected TKA in selected patients. No infection recurrence was observed during follow-up. |