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ID PMID Title PublicationDate abstract
33034255 Ligand-based pharmacophore modeling of TNF-α to design novel inhibitors using virtual scr 2022 Mar Tumor necrosis factor-α (TNF-α) is one of the promising targets for treating inflammatory (Crohn disease, psoriasis, psoriatic arthritis, rheumatoid arthritis) and various other diseases. Commercially available TNF-α inhibitors are associated with several risks and limitations. In the present study, we have identified small TNF-α inhibitors using in silico approaches, namely pharmacophore modeling, virtual screening, molecular docking, molecular dynamics simulation and free binding energy calculations. The study yielded better and potent hits that bind to TNF-α with significant affinity. The best pharmacophore model generated using LigandScout has an efficient hit rate and Area Under the operating Curve. High throughput virtual screening of SPECS database molecules against crystal structure of TNF-α protein, coupled with physicochemical filtration, PAINS test. Virtual hit compounds used for molecular docking enabled the identification of 20 compounds with better binding energies when compared with previously known TNF-α inhibitors. MD simulation analysis on 20 virtual identified hits showed that ligand binding with TNF-α protein is stable and protein-ligand conformation remains unchanged. Further, 16 compounds passed ADMET analysis suggesting these identified hit compounds are suitable for designing a future class of potent TNF-α inhibitors.Communicated by Ramaswamy H. Sarma.
33193425 Serological Evidence for the Association Between Epstein-Barr Virus Infection and Sjögren 2020 BACKGROUND: Exposure to Epstein-Barr virus (EBV) infection has been hypothesized to be an important risk factor for multiple rheumatic diseases, but the serological evidence so far for its role in Sjögren's syndrome (SjS) is not clearly established yet. This study aimed to assess the seroepidemiological associations of antibodies to EBV with SjS. METHODS: A seroepidemiological study containing 119 patients with SjS and 65 healthy controls was first performed, in which the associations of SjS with four commonly studied EBV antibodies including IgM-anti-viral capsid antigen (anti-VCA) antibody, IgG-anti-VCA antibody, IgG-anti-early antigen (anti-EA) antibody, and IgG-anti-EBV nuclear antigen 1 (anti-EBNA1) antibody were evaluated. A systematic review and meta-analysis of eligible seroepidemiological studies was also carried out, and data syntheses were performed using random-effect meta-analysis. RESULTS: In the case-control study, the patients with SjS had both a significantly higher prevalence of IgG-anti-EA antibody positivity (31.9% vs. 3.1%, P < 0.001) and high titers of IgG-anti-EA antibody (P < 0.001) than healthy controls. The titer of IgG-anti-VCA antibody was significantly increased in the patients with SjS compared with healthy controls (P < 0.001). IgG-anti-EA antibody seropositive patients with SjS had lower levels of both C3 (P = 0.002) and C4 (P = 0.02), and the titer of IgG-anti-EA antibody was inversely related to the levels of both C3 (r = -0.31, P < 0.001) and C4 (r = -0.20, P = 0.03). A total of 14 eligible studies on the serological associations between EBV infection and SjS were finally included into the meta-analysis, which suggested obvious associations of SjS with IgM-anti-VCA antibody [Odds ratio (OR) = 5.77, 95%CI 1.73-19.25, P = 0.004] and IgG-anti-EA antibody (OR = 9.97, 95%CI 4.58-21.67, P < 0.00001). CONCLUSIONS: The findings from this study provide strong serological evidence for the association between EBV infection and SjS. SjS has obvious associations with IgM-anti-VCA antibody and IgG-anti-EA antibody. IgG-anti-EA antibody is linked to low levels of C3 and C4 in the patients with SjS, the significance of which needs to be addressed in further studies.
31325310 Epigenetically quantified immune cells in salivary glands of Sjögren's syndrome patients: 2020 Feb 1 OBJECTIVE: To investigate whether epigenetic cell counting represents a novel method to quantify immune cells in salivary glands of patients with different forms of Sjögren's and sicca syndrome and to capture immunopathology and potentially aid in diagnosis. METHODS: DNA from frozen salivary gland tissue sections of sicca patients was used for bisulphite conversion of demethylated DNA cytosine residues, followed by cell-specific quantitative PCR to calculate cell percentages in relation to total tissue cell numbers as quantified by housekeeping gene demethylation. The percentages of epigenetically quantified cells were correlated to RNA expression of matched salivary gland tissue and histological and clinical parameters. RESULTS: The percentages of epigenetically quantified CD3, CD4, CD8, T follicular helper (Tfh) cells, FoxP3+ regulatory T cells and B cells were significantly increased in the salivary glands of patients with SS. Unsupervised clustering using these percentages identified patient subsets with an increased lymphocytic focus score and local B cell hyperactivity and classifies patients different from conventional classification criteria. In particular, Tfh cells were shown to strongly correlate with the expression of CXCL13, lymphocytic focus scores, local B cell hyperactivity and anti-SSA positivity. CONCLUSION: Epigenetic cell counting is a promising novel tool to objectively and easily quantify immune cells in the labial salivary gland of sicca patients, with a relatively small amount of tissue needed. In view of the potential of this technique to include a huge number of (cell-specific) biomarkers, this opens up new standardized ways of salivary gland analysis with high relevance for patient classification, understanding of immunopathology and monitoring of drug responses in clinical trials.
33276741 Idiopathic multicentric Castleman disease with Sjögren's syndrome and secondary membranou 2020 Dec 4 BACKGROUND: Idiopathic multicentric Castleman disease (iMCD) is an uncommon lymphoproliferative disorder and lacks treatment consensus. Herein, we report a case of iMCD complicated with Sjögren's syndrome (SS) and secondary membranous nephropathy (SMN). CASE PRESENTATION: A 45-year-old female with dry mouth for 3 months and anasarca and proteinuria for 2 months was admitted. She also experienced chest tightness, wheezing, fever, weight loss, moderate proteinuria and hypoalbuminemia. A computed tomography (CT) scan revealed a tissue mass in the thymus area and enlarged multiple lymph nodes. Her symptoms did not improve after resection of the thymus mass. The pathological findings were "reactive hyperplasia of the mediastinal lymph nodes and thymic hyperplasia". Lymph node biopsy findings confirmed iMCD with human herpes virus-8 (HHV-8) negativity. Based on anti-nuclear antibody (ANA) 1:320, anti-SSA and anti-SSB antibody positivity, salivary flow less than 0.1 ml/min and lip biopsy with focal lymphocytic sialadenitis, SS was diagnosed. Kidney biopsy showed secondary membranous nephropathy with endocapillary cell proliferation and infiltration of plasma cells and lymphocytes in the tubulointerstitium. Serum interleukin-6 (IL-6) levels were significantly increased, and therapy with tocilizumab (anti-IL-6 receptor antibody) worked well. The combination of cyclophosphamide (CyS) with methylprednisolone (MP) maintained satisfactory remission. CONCLUSIONS: Our case of iMCD with SS and SMN is rare. There is a need for increased awareness of the disease to avoid unnecessary procedures and misdiagnoses. IL-6 was extremely high, and there was a rapid response to anti-IL-6 receptor agents. The combination of CyS with MP maintained complete remission.
32502475 Increased levels of BPI-ANCA in patients with primary Sjögren's syndrome are associated w 2020 Sep BACKGROUND: The goal of this study was to investigate the association between bactericidal permeability increasing (BPI)-antineutrophil cytoplasmic antibody (ANCA) protein levels and primary Sjogren's syndrome (pSS) with lung involvement, as well as the potential diagnostic performance of BPI-ANCA. METHODS: The levels of BPI-ANCA in pSS patients with (n = 36) and without (n = 85) lung involvement were measured using a commercial ELISA kit. Serological biomarkers and cytokines were measured in these patients as well. Lung involvement was determined by high-resolution computed tomography (HRCT) and/or clinical symptoms. The diagnostic performance of lung involvement was determined by receiver operating characteristic (ROC) curves. RESULTS: The percentage of neutrophils (NEUT%), neutrophil-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), and the levels of BPI-ANCA, C-reactive protein (CRP), interleukin-2 (IL-2) and IL-6 exhibited an upward trend, while the percentage of lymphocytes (LYMP%) and albumin (ALB) level exhibited a downward trend in the lung involvement group. The combination of BPI-ANCA, NEUT% and ALB significantly increased the area under the ROC curve (AUC) to 0.837 (95% confidence interval: 0.742-0.907, sensitivity: 82.14%, specificity: 81.36%, P < 0.001). CONCLUSIONS: Increased BPI-ANCA was found in pSS patients with lung involvement and was associated with inflammation. A combination of BPI-ANCA, NEUT% and ALB had the best AUC, and may serve as anadjunct to distinguish between pSS patients with and without lung involvement.
32487532 Primary Sjogren's syndrome manifesting with distal renal tubular acidosis and severe metab 2020 Jun 1 Sjogren's syndrome (SS) is a chronic, autoimmune, inflammatory disorder affecting primarily the salivary and lacrimal glands with potential for systemic involvement. The disease predominantly occurs in women in the age group of 35-45 years and is relatively rare in children. It mainly affects salivary and lacrimal glands with potential for systemic involvement. Children presenting with the severe metabolic bone disease at the very outset has not been reported in the paediatric literature. We report a 13-year-old girl who presented with pain in multiple large joints with predominant involvement of hip joints leading to difficulty in walking for the past 6 months and unintentional weight loss of the same duration. Investigations revealed distal renal tubular acidosis with severe metabolic bone disease as an extra-glandular manifestation of primary SS.
32291887 Clinical efficacy and safety of certolizumab pegol in cutaneous symptoms on psoriasis in p 2020 May We present the results on retrospective analysis about the efficacy of Certolizumab pegol (CZP), an antitumor necrosis factor-alpha agent, as monotherapy on skin psoriasis (PsO) in patients affect both by psoriatic arthritis (PsA) and mild-severe PsO. To date, the CZP is authorized for the treatment of PsA, PsO beyond that rheumatoid arthritis, axial spondyloarthritis/ankylosing spondylitis, and Crohn's. Assessments included an evaluation of the Psoriasis Area and Severity Index (PASI). Twelve patients (9M and 3F mean age 57.8 ± 8 years) were enrolled in our study. Nine patients had been previously treated with others biologic agents, three patients were naïve. Clinical and laboratory evaluations including PASI, erythrosedimentation rate, and C-reactive protein were performed at baseline (BL), at Week 12 (W12), Week 24 (W24), and Week 52 (W52) of treatment. Although the combination between methotrexate and CZP is allowed, we included, in our study, patients treated only with CZP. In such a way as to be as specific as possible, topical corticosteroids, vitamin D derivatives, retinoid creams, anthralin derivatives as well as p-UVA or UV-B have been forbidden to enrolled patients. With the same purpose, all the patients used the identical moisturizing cream two times a day. Mean PASI score decreased from 18 (BL) to 0 (W52) as follows: 18 at BL, 4 at W12, 0 at W24, and 0 at W52. Severe adverse events were not reported. Safety evaluations were performed every 3 months: liver and renal functions were monitored in all patients during the treatment, and no patient presented abnormal values. To the best of our knowledge, this is the first report that highlights the efficacy of CZP as monotherapy in psoriasis with mild to severe cutaneous involvement. Although to date the drug is authorized only for PsA, our results demonstrate that CZP is safe and effective on both cutaneous and joint components representing, therefore, an effective option in the treatment of cutaneous symptoms of PsO. Limitations of our study are presented by the relatively short observation time (W52) and by numeric small study group. Long-term data with a larger number of enrolled patients are necessary in order to confirm our preliminary observations.
32208441 Dysbiotic oral microbiota and infected salivary glands in Sjögren's syndrome. 2020 Key events in the pathogenesis of Sjӧgren syndrome (SS) include the change of salivary gland epithelial cells into antigen-presenting cell-like phenotypes and focal lymphocytic sialadenitis (FLS). However, what triggers these features in SS is unknown. Dysbiosis of the gut and oral microbiomes is a potential environmental factor in SS, but its connection to the etiopathogenesis of SS remains unclear. This study aimed to characterize the oral microbiota in SS and to investigate its potential role in the pathogenesis of SS. Oral bacterial communities were collected by whole mouthwash from control subjects (14 without oral dryness and 11 with dryness) and primary SS patients (8 without oral dryness and 17 with dryness) and were analyzed by pyrosequencing. The SS oral microbiota was characterized by an increased bacterial load and Shannon diversity. Through comparisons of control and SS in combined samples and then separately in non-dry and dry conditions, SS-associated taxa independent of dryness were identified. Three SS-associated species and 2 control species were selected and used to challenge human submandibular gland tumor (HSG) cells. Among the selected SS-associated bacterial species, Prevotella melaninogenica uniquely upregulated the expression of MHC molecules, CD80, and IFNλ in HSG cells. Concomitantly, P. melaninogenica efficiently invaded HSG cells. Sections of labial salivary gland (LSG) biopsies from 8 non-SS subjects and 15 SS patients were subjected to in situ hybridization using universal and P. melaninogenica-specific probes. Ductal cells and the areas of infiltration were heavily infected with bacteria in the LSGs with FLS. Collectively, dysbiotic oral microbiota may initiate the deregulation of SGECs and the IFN signature through bacterial invasion into ductal cells. These findings may provide new insights into the etiopathogenesis of SS.
32020767 Anti-TNF treatment during pregnancy and birth outcomes: A population-based study from Denm 2020 Mar PURPOSE: To study the risk of preterm birth, caesarean section, and small for gestational age after anti-tumor necrosis factor agent treatment (anti-TNF) in pregnancy. METHODS: Population-based study including women with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis, and their infants born 2006 to 2013 from the national health registers in Denmark, Finland, and Sweden. Women treated with anti-TNF were compared with women with nonbiologic systemic treatment. Adalimumab, etanercept, and infliximab were compared pairwise. Continuation of treatment in early pregnancy was compared with discontinuation. Odds ratios with 95% confidence intervals were calculated in logistic regression models adjusted for country and maternal characteristics. RESULTS: Among 1 633 909 births, 1027 infants were to women treated with anti-TNF and 9399 to women with nonbiologic systemic treatment. Compared with non-biologic systemic treatment, women with anti-TNF treatment had a higher risk of preterm birth, odds ratio 1.61 (1.29-2.02) and caesarean section, 1.57 (1.35-1.82). The odds ratio for small for gestational age was 1.36 (0.96-1.92). In pairwise comparisons, infliximab was associated with a higher risk of severely small for gestational age for inflammatory joint and skin diseases but not for inflammatory bowel disease. Discontinuation of anti-TNF had opposite effects on preterm birth for inflammatory bowel disease and inflammatory joint and skin diseases. CONCLUSIONS: Anti-TNF agents were associated with increased risks of preterm birth, caesarean section, and small for gestational age. However, the diverse findings across disease groups may indicate an association related to the underlying disease activity, rather than to agent-specific effects.
32966314 TRI microparticles prevent inflammatory arthritis in a collagen-induced arthritis model. 2020 Despite recent progress in the treatment of rheumatoid arthritis (RA), many patients still fail to achieve remission or low disease activity. An imbalance between auto-reactive effector T cells (Teff) and regulatory T cells (Treg) may contribute to joint inflammation and damage in RA. Therefore, restoring this balance is a promising approach for the treatment of inflammatory arthritis. Accordingly, our group has previously shown that the combination of TGF-β-releasing microparticles (MP), rapamycin-releasing MP, and IL-2-releasing MP (TRI MP) can effectively increase the ratio of Tregs to Teff in vivo and provide disease protection in several preclinical models. In this study TRI MP was evaluated in the collagen-induced arthritis (CIA) model. Although this formulation has been tested previously in models of destructive inflammation and transplantation, this is the first model of autoimmunity for which this therapy has been applied. In this context, TRI MP effectively reduced arthritis incidence, the severity of arthritis scores, and bone erosion. The proposed mechanism of action includes not only reducing CD4+ T cell proliferation, but also expanding a regulatory population in the periphery soon after TRI MP administration. These changes were reflected in the CD4+ T cell population that infiltrated the paws at the onset of arthritis and were associated with a reduction of immune infiltrate and inflammatory myeloid cells in the paws. TRI MP administration also reduced the titer of collagen antibodies, however the contribution of this reduced titer to disease protection remains uncertain since there was no correlation between collagen antibody titer and arthritis score.
32208438 Associations of inflammatory markers with impaired left ventricular diastolic and systolic 2020 BACKGROUND: High-grade inflammation may play a pivotal role in the pathogenesis of left ventricular (LV) dysfunction. Evidence to support a role of systemic inflammation in mediating impaired LV function in experimental models of rheumatoid arthritis (RA) remains limited. The aim of the present study was to determine the effects of high-grade systemic inflammation on LV diastolic and systolic function in collagen-induced arthritis (CIA). METHODS: To induce CIA, bovine type-II collagen emulsified in incomplete Freund's adjuvant was injected at the base of the tail into 21 three-month old Sprague Dawley rats. Nine-weeks after the first immunisation, LV function was assessed by pulsed Doppler, tissue Doppler imaging and Speckle tracking echocardiography. Cardiac collagen content was determined by picrosirius red staining; circulating inflammatory markers were measured using ELISA. RESULTS: Compared to controls (n = 12), CIA rats had reduced myocardial relaxation as indexed by lateral e' (early diastolic mitral annular velocity) and e'/a' (early-to-late diastolic mitral annular velocity) and increased filling pressures as indexed by E/e'. No differences in ejection fraction and LV endocardial fractional shortening between the groups were recorded. LV global radial and circumferential strain and strain rate were reduced in CIA rats compared to controls. Higher concentrations of circulating inflammatory markers were associated with reduced lateral e', e'/a', radial and circumferential strain and strain rate. Greater collagen content was associated with increased concentrations of circulating inflammatory markers and E/e'. CONCLUSION: High-grade inflammation is associated with impaired LV diastolic function and greater myocardial deformation independent of haemodynamic load in CIA rats.
31648579 Indonesians Human Leukocyte Antigen (HLA) Distributions and Correlations with Global Disea 2020 Apr In Human, Major Histocompatibility Complex known as Human Leukocyte Antigen (HLA). The HLA grouped into three subclasses regions: the class I region, the class II region, and the class III region. There are thousands of polymorphic HLAs, many of them are proven to have correlations with diseases. Indonesia consists of diverse ethnicity people and populations. It carries a unique genetic diversity between one and another geographical positions. This paper aims to extract Indonesians HLA allele data, mapping the data, and correlating them with global diseases. From the study, it is found that global diseases, like Crohn's disease, rheumatoid arthritis, Graves' disease, gelatin allergy, T1D, HIV, systemic lupus erythematosus, juvenile chronic arthritis, and Mycobacterial disease (tuberculosis and leprosy) suspected associated with the Indonesian HLA profiles.
33581033 Reduced joint awareness after total knee arthroplasty with a cruciate retaining design. 2020 Sep A range of different total knee arthroplasty (TKA) designs have been developed, each specifically designed to relieve pain and restore knee function with the greatest possible patient satisfaction. The purpose of this study was to compare a posterior stabilized design and a cruciate-retaining design. We hypothesized that a cruciate-retaining design would have a higher Forgotten Joint Score (FJS) than a posterior stabilized design. Ninety-two patients were used in our analysis (46 patients in each group) involving TKA (Attune, Depuy-Synthes) between January 2014 and March 2015. We excluded patients with valgus alignment, post-traumatic arthritis, rheumatoid arthritis and major previous surgery on the knee. We compared the FJS, the Oxford Knee Score (OKS) and their ceiling effects. FJS was significantly higher in the fixed-bearing cruciate-retaining group (P=0.043). The mean (-SD) FJS for the cruciate-retaining group was 78,4-25.1 compared to 67.6-27.6 for the posterior stabilized group. No significant difference in OKS was detected. The total ceiling effect for FJS and OKS was 32.2% and 45.5%, respectively. In conclusion, patients with cruciate-retaining TKA showed a better FJS in comparison to posterior stabilized TKA. FJS has a higher discriminatory power compared to OKS.
32283509 The off-label uses profile of tofacitinib in systemic rheumatic diseases. 2020 Jun Tofacitinib is an oral, small molecule JAK inhibitor that targets JAK1/JAK3. Tofacitinib has been approved by the FDA to be used in the treatments of rheumatoid arthritis, psoriatic arthritis, plaque psoriasis and ulcerative colitis. Considering the important pathogenic role of the JAK/STAT pathway in autoimmune disease, tofacitinib could be, theoretically, effective in the treatments of other systemic rheumatic diseases. Here we reviewed the published literature to profile the perspectives about the off-label uses of tofacitinib, especially in those refractory cases with poor response to conventional therapies or biologic agents. Tofacitinib can be a new therapeutic option and help reducing hormone dependence and correlated adverse events.
32857321 Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induce 2020 Dec Monocytes' plasticity has an important role in the development of rheumatoid arthritis (RA), an autoimmune disease exhibiting greater prevalence in women. Contribution of this phenomenon to sex bias in RA severity was investigated in rat collagen-induced arthritis (CIA) model of RA. The greater severity of CIA in females (exhibiting signs of bone resorption) was accompanied by the higher blood level of advanced oxidation protein products and a more pro-oxidant profile. Consistently, in females, the greater density of giant multinuclear cells (monocytes/macrophages and osteoclasts) in inflamed joint tissue was found. This correlated with the higher frequencies of CCR2- and CX3CR1- expressing cells (precursors of inflammatory monocytes/macrophages and osteoclasts) among CD11b+ splenocytes. This in conjunction with the enhanced migratory capacity of CD11b+ monocytic cells in females compared with males could be linked with the higher frequencies of CCR2+CX3CR1-CD43(low)CD11b+ and CCR2-CX3CR1+CD43(hi)CD11b+ cells (corresponding to "classical" and "non-classical" monocytes, respectively) and the greater density of CD68+ cells (monocytes/macrophages and osteoclast precursors/osteoclasts) in blood and inflamed paws from female rats, respectively. Consistently, the higher levels of GM-CSF, TNF-α and IL-6, IL-1β (driving Th17 cell differentiation), and IL-17 followed by the lower level of IL-10 were measured in inflamed paw cultures from female compared with male rats. To the greater IL-17 production (associated with enhanced monocyte immigration and differentiation into osteoclasts) most likely contributed augmented Th17 cell generation in the lymph nodes draining arthritic joints from female compared with male rats. Overall, the study suggests the sex-specific contribution of monocytic lineage cells to CIA, and possibly RA development.
32183053 The Interrelations between Biological and Targeted Synthetic Agents Used in Inflammatory J 2020 Mar 13 Obesity is a comorbidity that plays a role in the development and severity of inflammatory joint diseases, including rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis. The relationships between obesity and adipose tissue and the treatments given for inflammatory joint diseases are bidirectional. In fact, biological agents (bDMARDs) and targeted synthetic agents (tsDMARDs) may influence body weight and body composition of treated patients, while obesity in turn may influence clinical response to these agents. Obesity is a prevalent comorbidity mainly affecting patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) with specific phenotypes. Tumour necrosis factor alpha (TNFα) inhibitors have been associated with changes in body composition by improving lean mass, but also by significantly increasing fat mass, which localized toward the abdominal/visceral region. The IL-6 inhibitor tocilizumab is associated with an increase in lean mass without change in fat mass. The clinical response to TNFα inhibitors is attenuated by obesity, an effect that is less pronounced with IL-6 inhibitors and the B-cell depletion agent rituximab. Conversely, body weight has no influence on the response to the costimulation inhibitor abatacept. These effects may be of help to the physician in personalized medicine, and may guide the therapeutic choice in obese/overweight patients.
32594339 Inflammation suppression by dexamethasone via inhibition of CD147-mediated NF-κB pathway 2020 Oct Dexamethasone (Dex) exhibits broad-spectrum anti-inflammatory effects in chronic destructive rheumatoid arthritis. We present in vivo and in vitro evidence supporting the preventive effects and underlying mechanisms of Dex on collagen-induced arthritis (CIA)-induced synovial injuries. After successful induction of CIA, Wistar rats were administered Dex intraperitoneally (1 mg/kg) three times a week for more than 2 weeks. In vivo, paw swelling, arthritis scores, and histological evaluations were analyzed to determine the therapeutic effects of Dex on the progression of arthritis. In vitro, CIA fibroblast-like synoviocytes (FLSs) were treated for 48 h with vehicle (control group), 10 ng/mL IL-1α (IL-1α group), 10 ng/mL IL-1α + 10 μM Dex (Dex group), or 10 ng/mL IL-1α + 10 μg/mL anti-CD147 antibody (anti-CD147 group). Evaluations of FLSs proliferation, cell cycle, migration, gene expression of Cyclin D1, p27, p57, interleukin (IL)-1β, IL-6, IL-17, tumor necrosis factor (TNF)-α, CD147, CypB, matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-13, ROS generation, protein expression of NF-κB and CD147, and translocation of NF-κB p65 were all conducted. The in vivo results showed that arthritis intensity was attenuated in the Dex-treated group. The in vitro findings demonstrated that treatment with Dex induced G0/G1 arrest and suppressed proliferation, migration, gene expression of IL-1β, IL-6, IL-17, TNF-α, CD147, CypB, MMP-3, MMP-9, and MMP-13, ROS generation and protein expression of NF-κB and CD147. Translocation of NF-κB p65 was inhibited by both Dex and anti-CD147 monoclonal antibody treatment. We offer molecular evidence of the anti-rheumatism efficacy Dex through hindrance to CD147, splendidly stabilization of the oxidative stress by downregulating the NF-κB signaling pathway.
33241646 Similar Impact of Psoriatic Arthritis and Rheumatoid Arthritis on Objective and Subjective 2020 Dec OBJECTIVE: The objective of this study was to compare the impact of psoriatic disease (psoriatic arthritis [PsA] and psoriasis) and rheumatoid arthritis (RA) on objective and subjective parameters of hand function. METHODS: Hand function was determined in this cross-sectional study by 1) vigorimetric grip strength, 2) the Moberg Picking-Up Test used for assessing fine-motor skills, and 3) self-reported hand function (Michigan Hand Questionnaire). Mixed-effects linear regression models were used to test the relation of hand function with disease group, age, and sex. RESULTS: Two hundred ninety-nine subjects were tested, 101 with RA, 92 with PsA, and 106 nonarthritic controls (51 with psoriasis and 55 healthy controls [HCs]). Regression analysis showed that hand function was influenced by age, sex, disease group, and hand dominance (P < 0.001 for all). The impact of PsA and RA on hand function was comparable and generally more pronounced in women. Both PsA and RA led to significantly enhanced age-related loss of grip strength, fine-motor skills, and self-reported hand function in patients with PsA and RA compared with HCs. In addition, patients with psoriasis showed significant impairment of hand function compared with HCs. CONCLUSION: RA and PsA have a comparable impact on the decline of strength, fine-motor skills, and self-reported function of the hand. Unexpectedly, patients with psoriasis also show impaired hand function that follows a similar pattern as observed in patients with PsA.
32546977 Using a Discrete-Choice Experiment in a Decision Aid to Nudge Patients Towards Value-Conco 2020 PURPOSE: To evaluate, in a proof-of-concept study, a decision aid that incorporates hypothetical choices in the form of a discrete-choice experiment (DCE), to help patients with early rheumatoid arthritis (RA) understand their values and nudge them towards a value-centric decision between methotrexate and triple therapy (a combination of methotrexate, sulphasalazine and hydroxychloroquine). PATIENTS AND METHODS: In the decision aid, patients completed a series of 6 DCE choice tasks. Based on the patient's pattern of responses, we calculated his/her probability of choosing each treatment, using data from a prior DCE. Following pilot testing, we conducted a cross-sectional study to determine the agreement between the predicted and final stated preference, as a measure of value concordance. Secondary outcomes including time to completion and usability were also evaluated. RESULTS: Pilot testing was completed with 10 patients and adjustments were made. We then recruited 29 patients to complete the survey: median age 57, 55% female. The patients were all taking treatment and had well-controlled disease. The predicted treatment agreed with the final treatment chosen by the patient 21/29 times (72%), similar to the expected agreement from the mean of the predicted probabilities (68%). Triple therapy was the predicted treatment 24/29 times (83%) and chosen 20/29 (69%) times. Half of the patients (51%) agreed that completing the choice questions helped them to understand their preferences (38% neutral, 10% disagreed). The tool took an average of 15 minutes to complete, and median usability scores were 55 (system usability scale) indicating "OK" usability. CONCLUSION: Using a DCE as a value-clarification task within a decision aid is feasible, with promising potential to help nudge patients towards a value-centric decision. Usability testing suggests further modifications are needed prior to implementation, perhaps by having the DCE exercises as an "add-on" to a simpler decision aid.
32993066 Blocking IL-17: A Promising Strategy in the Treatment of Systemic Rheumatic Diseases. 2020 Sep 26 Systemic rheumatic diseases are a heterogeneous group of autoimmune disorders that affect the connective tissue, characterized by the involvement of multiple organs, leading to disability, organ failure and premature mortality. Despite the advances in recent years, the therapeutic options for these diseases are still limited and some patients do not respond to the current treatments. Interleukin-17 (IL-17) is a cytokine essential in the defense against extracellular bacteria and fungi. Disruption of IL-17 homeostasis has been associated with the development and progression of rheumatic diseases, and the approval of different biological therapies targeting IL-17 for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) has highlighted the key role of this cytokine. IL-17 has been also implicated in the pathogenesis of systemic rheumatic diseases, including systemic lupus erythematosus (SLE), Sjögren's syndrome (SS) and systemic sclerosis (SSc). The aim of this review is to summarize and discuss the most recent findings about the pathogenic role of IL-17 in systemic rheumatic and its potential use as a therapeutic option.