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ID PMID Title PublicationDate abstract
33095139 Ianalumab (VAY736) in primary Sjögren's syndrome: assessing disease activity using multi- 2020 Jul OBJECTIVES: To apply serial ultrasound (US) assessments to show effects of ianalumab (anti-BAFF-R monoclonal antibody) on inflamed salivary glands of patients with primary Sjögren's syndrome (pSS). METHODS: In a single-centre, 24-week double-blind study (NCT02149420), 27 pSS patients of moderate-to-severe activity were randomly assigned to receive a single i.v. dose of either 3 mg/kg or 10 mg/kg ianalumab, or placebo. Concurrent with clinical and laboratory outcomes, multi-modal US images were acquired of bilateral parotid glands (PG) and submandibular glands (SMG) at weeks 0, 6, 12, and 24. Applied US modalities included 1) B-mode echostructure scored by de Vita classification, 2) macrovascular blood flow by power Doppler, and in PG only 3) microvascularisation using contrast-enhanced US (area under the curve, time to peak or TTP) and 4) gland stiffness by sonoelastography. RESULTS: Clinical study results were previously published. US data for PG differed from SMG but were comparable between respective left and right sides of these glands. Numerical improvements in salivary gland quality and declining tissue inflammation were observed in treated versus placebo groups, including more patients achieving ≥1-point reduction from baseline in De Vita score, together with trends towards decreased perfusion and stiffness. Correlations between clinical endpoints and US parameters were largely restricted to microvascular perfusion TTP and at the 12-week timepoint when ianalumab effects were predicted at maximal. CONCLUSIONS: Early in vivo signs of salivary gland improvement in response to an effective intervention can be shown without need of biopsy by using a non-invasive, comprehensive, ultrasound-based approach over multiple time points.
32943063 Utility of the EULAR Sjögren syndrome disease activity index in Japanese children: a retr 2020 Sep 17 BACKGROUND: The European League Against Rheumatism (EULAR) Sjögren Syndrome Disease Activity Index (ESSDAI) has been utilized to assess Sjögren syndrome-related systemic involvement in adult patients. To date, however, the ESSDAI has not been validated in children with primary Sjögren's syndrome. This study evaluated the applicability of the ESSDAI to Japanese children with primary Sjögren's syndrome. METHODS: The medical records of children who had been diagnosed with Sjogren syndrome at age ≤ 16 years between June 2011 and October 2016 were collected, and their ESSDAIs at initial presentation were calculated. Clinical symptoms and treatment regimens were surveyed by questionnaire, and patients were divided into groups based on ESSDAI and glucocorticoid dosages. The associations of ESSDAI scores with treatment regimens were analyzed statistically. RESULTS: The study subjects included 31 children (3 boys, 28 girls) with primary Sjögren's syndrome. Their median age at disease onset was 10 years (interquartile range [IQR], 8-13 years), and their median initial ESSDAI was 7.0 (IQR; 5.0-15.0). ESSDAI-determined disease activity was high in nine patients (29.0%), moderate in 15 (48.4%), and low in seven (22.6%). During the first year after their initial visit, 14 patients (45.2%) were treated with prednisolone (PSL) and six (19.4%) with immunosuppressants. Dose of PSL was significantly associated with ESSDAI score. Median ESSDAI score was significantly higher in patients treated with high/medium- than with no/low-dose PSL (16.5 [IQR 10.5-18.0] vs 5.0 [IQR 3.0-8.5]). Eight (66.7%) of 12 patients administered medium/high-dose PSL and one (5.3%) of 19 administered no/low-dose PSL had high disease activity on ESSDAI. CONCLUSION: Disease activity assessed by ESSDAI tended to be consistent with disease activity assessed by pediatric rheumatologists in determining treatment regimens. ESSDAI is useful for assessing disease activity in Japanese children with primary Sjögren's syndrome.
32130578 Macrophage activation syndrome associated with adult-onset Still's disease: a multicenter 2020 Aug OBJECTIVES: To explore the clinical features, treatments, and prognostic factors of adult-onset Still's disease (AOSD)-associated macrophage activation syndrome (MAS), we conducted a multicenter retrospective clinical study of AOSD-associated MAS patients. METHODS: AOSD patients were collected from six tertiary hospitals in China. Medical charts were reviewed and clinical information was recorded and analyzed. RESULTS: There were 447 AOSD patients enrolled into this retrospective clinical study. Among them, 55 were diagnosed with MAS. Liver dysfunction was the most reliable predictive factor for the screening of MAS in AOSD patients (OR = 75.744, 95%CI = 23.015-249.284, p < 0.0001). In multivariate analysis, clinical features including platelets < 100 × 10(9)/L (OR = 9.546, p = 0.005), aspartate transaminase (AST) > 120 U/L (OR = 25.853, p < 0.0001), triglycerides > 3 mmol/L (OR = 12.9833, p = 0.011)), ferritin > 1500 ng/mL (OR = 5.513, p = 0.050), as well as hemophagocytosis in bone puncture (OR = 18.132, p = 0.001) were highly associated with the occurrence of MAS. The mortality rate of total AOSD patients was 4.47%, MAS was the main cause of death in AOSD patients (OR = 11.705, 95%CI = 4.783-28.647, p < 0.0001). PLT ≤ 100 × 10(9)/L (p = 0.0001), fibrinogen < 1.5 g/L (p = 0.0286), splenomegaly (p = 0.0002), and liver dysfunction (p = 0.0008) highly suggested poor prognosis. CONCLUSION: MAS occurrence is the major cause of death in AOSD patients. Notable liver dysfunction, as well as splenomegaly, low number of platelets or neutrophils, high levels of serum ferritin, and reduced level of fibrinogen are risk factors for poor outcome. Key Points • This is a multicenter retrospective study of AOSD-associated MAS with large number of cases.
31863212 A patient with primary Sjogren's syndrome, cystic lung disease, and MALT lymphoma treated 2020 Apr Primary Sjogren's syndrome (pSS) can have a myriad of presentations, ranging from mild xerostomia to more diffuse systemic involvement. It is well established that pSS is associated with a variety of pulmonary pathologies, and it is also known that pSS patients are at higher risk for lymphoma development. Here, we present an unusual case of a woman with primary Sjogren's syndrome who had both diffuse cystic lung disease as well as extranodal MALT lymphoma, successfully treated for both conditions with the CD-20 monoclonal antibody rituximab.
32876903 Efficacy and Safety of Baricitinib in Chinese Rheumatoid Arthritis Patients and the Subgro 2020 Dec INTRODUCTION: Baricitinib is an oral selective inhibitor of Janus kinase (JAK) 1 and JAK 2, which has demonstrated significant efficacy in patients with moderately to severely active rheumatoid arthritis (RA). This analysis aims to describe the efficacy and safety of baricitinib in Chinese RA patients with an inadequate response to methotrexate (MTX-IR), and to analyze the effects of baseline characteristics on the efficacy of baricitinib treatment. METHODS: In this 52-week, randomized, double-blind, placebo-controlled study, 231 Chinese patients with moderately to severely active RA who had MTX-IR were randomly assigned to placebo (n = 115) or baricitinib 4 mg once daily (n = 116). The primary endpoint was American College of Rheumatology 20% (ACR20) response at week 12. Other efficacy measures included ACR50, ACR70, Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, patient's assessment of pain, Disease Activity Score in 28 joints using high-sensitivity C-reactive protein, remission and low disease activity rates according to Simplified Disease Activity Index or Clinical Disease Activity Index, Health Assessment Questionnaire-Disability Index, and mean duration and severity of morning joint stiffness, worst tiredness and worst joint pain were analyzed. Additionally, subgroup analyses were performed across baseline characteristics. RESULTS: Statistically significant improvement in ACR20 response was achieved with baricitinib at week 12 (53.4 vs. 22.6%, p = 0.001) in Chinese patients, compared to placebo. Most of the secondary objectives were met with statistically significant improvements. Efficacy of baricitinib was irrespective of patient demographics and baseline characteristics. Safety events were similar between the baricitinib and placebo groups. CONCLUSIONS: The efficacy of baricitinib 4 mg in Chinese patients with moderately to severely active RA and prior MTX-IR was clinically significant compared to placebo regardless of baseline characteristics. Baricitinib was well tolerated with an acceptable safety profile during the full study period. TRIAL REGISTRATION: NCT02265705.
32608054 Cognitive dysfunction in Sjögren's syndrome using the Montreal Cognitive Assessment Quest 2020 Aug AIM: To describe the prevalence of cognitive impairment and the most affected cognitive domains, employing the Montreal Cognitive Assessment (MoCA) and the Automated Neuropsychological Assessment Metrics (ANAM) of a Latin American primary Sjögren's syndrome (pSS) cohort, and compare these patients to secondary Sjögren's syndrome (sSS) subjects and controls. METHODS: This was a comparative cross-sectional study of patients with a diagnosis of pSS who fulfilled the American-European Consensus Group 2002 criteria and/or American College of Rheumatology/European League Against Rheumatism 2016 criteria; clinical information was evaluated prior to cognitive evaluation, which consisted of a single session in which the MoCA and ANAM were applied. RESULTS: A total of 122 subjects were included in the analysis (51 pSS, 20 sSS and 51 controls); mean age of pSS was 56 years (SD 10.4), of which 47 (92.15%) were women. Moderate-severe cognitive impairment by MoCA was 17% in pSS, 5% in sSS, and 15% in controls, and by ANAM were 29% in pSS and 10% in sSS (P > .05). Visuospatial/executive subdomain in the MoCA was different between the pSS and the control group (P = .005). We encountered a statistically significant difference between pSS patients and control scores from the program in 6 of the 7 domains tested by the ANAM. CONCLUSION: No difference was found in the prevalence of cognitive impairment between pSS subjects and controls by MoCA. Several subdomain scores differed between groups in both scales. Evaluation of cognitive disorders in patients with SS, even in early stages of the disease, seems advisable but the best strategy is yet to be elucidated.
31838639 Persistent serological activity in primary Sjögren's syndrome. 2020 Mar To assess the presence of persistent serological activity and its association with clinical outcomes in primary Sjögren's syndrome. Clinical charts of 275 patients were reviewed retrospectively. Persistent serological activity was defined as an increase IgG ≥ 1.6 mg/dL or globulins > 3.7 g/dL or diminished C3 < 52 mg/dL or C4 < 12 mg/dL at least during two consecutive visits during a year (index period). The ClinESSDAI at the index period and the cumulative ClinESSDAI and the SSDDI at the last medical appointment were scored. A total of 159 patients with complete serological data were included mostly women and median disease duration of 10.2 years. Persistent serological activity was identified in 85 patients (53.1%). Only 13 patients changed their status to serological inactivity though the follow-up. Comparison of patients with (n = 85) versus without persistent serological activity (n = 74) showed that the first group had a higher frequency of impaired non-stimulated salivary flow, anti-La/SSB antibody, and RF, as well as higher ClinESSDAI scores. The most affected domains were the constitutional, glandular, cutaneous, renal, and hematological domains. On logistic regression analysis, the RF (OR 6.4, 95% CI 1.8-22, p = 0.003), the renal (OR 12.8, 95% CI 1.7-92, p = 0.01), and the hematological involvement (OR 4.7, 95% CI 1.6-13.4, p = 0.004) remained associated. Half of the patients studied had persistent serological activity, being this status constant through the follow-up. Persistent serological activity was associated with positive RF and higher ESSDAI scores due to hematological and renal activity. Scoring serological activity is an important issue in SS patients.
33099041 Minor salivary gland biopsy: Its role in the classification and prognosis of Sjögren's sy 2020 Dec Sjögren's syndrome (SS) is an autoimmune disorder characterized by mononuclear cell infiltration in the exocrine glands, which leads to sicca syndrome (xerostomia and xerophthalmia). The etiology of SS is unknown, but multiple environmental factors (infectious, hormonal and stress-related), as well as genetic factors, may play a role in its pathogenesis. The diagnosis of SS is complex considering its clinical and paraclinical parameters may not be very specific. The minor salivary gland biopsy (MSGB) has undoubtedly become crucial for classifying and determining the prognosis of SS. The three main different classification systems for its interpretation have been described by Chisholm and Mason, Greenspan and Daniels, and Tarpley. However, this invasive procedure has variable sensitivity and specificity as well as low reproducibility. The use of additional methods, such as skin biopsy, imaging techniques, and serum/salivary biomarkers, may be combined with current methods to develop a bioscore that could increase diagnostic performance. In this review, we summarized the main pathological findings in SS and the prognosis of patients with SS according to the biopsy results.
33025898 Recent insights in the potential role of imaging modalities for diagnosing patients with p 2020 Jul Within the last year, interesting developments regarding the assessment of salivary gland involvement in patients with clinical suspicion of, or diagnosed with primary Sjögren's syndrome (pSS) have been performed. In this review various topics will be discussed, starting with the use of salivary gland ultrasonography (SGUS) for the detection of glandular swelling. Furthermore, other imaging modalities, besides B-mode SGUS, which differentiate between pSS patients and healthy controls will be highlighted. Moreover, storage of ultrasonographic images and videos will be discussed briefly, as will be some potential biases and pitfalls. Finally, efforts that have been made to make incorporation of SGUS into the most recent classification criteria possible will be discussed, as well as the important steps that have been taken to develop a new semi-quantitative scoring system for the assessment of salivary gland involvement in patients with suspected or confirmed pSS.
33025895 Characterisation of articular manifestations in primary Sjögren's syndrome: clinical and 2020 Jul OBJECTIVES: Articular manifestations (AMs) are observed in a large proportion of patients with primary Sjögren's syndrome (pSS) and can occur at the time of pSS diagnosis or during the disease course. Although in the majority of cases AMs are mild and self-limiting, some patients may experience chronic polyarthritis requiring treatment with DMARDs. Ultrasonography (US) and magnetic resonance imaging (MRI) can help assessing the extent of articular involvement and guide the treatment. The aim of this study was to describe clinical, serological, and histological picture of a cohort of pSS patients with AMs. METHODS: Clinical and serological records were retrospectively evaluated and either US or MRI were performed to evaluate AMs and their features were described according to the OMERACT scoring systems. RESULTS: One hundred and thirty-three pSS patients were enrolled, of whom 115 (86%) with articular involvement. In particular, 91 patients (68%) displayed AMs at the time of pSS diagnosis while 24 patients (32%) during the course of the disease. Patients with AMs during the disease course were diagnosed with pSS at a younger age and reported a higher VAS dryness compared to patients displaying AMs at pSS onset. Hands and wrists were the most frequently involved sites followed by knees, shoulders and ankles. Overall, a consistent number of abnormalities were detected, more by MRI than US. Hands and wrists were the most frequently evaluated sites and the prevalence of all MRI abnormalities was similar between the different sites and comparable between the groups. CONCLUSIONS: pSS AMs encompass a wide disease spectrum ranging from arthralgia to erosive arthritis resembling RA and therefore represent an important determinant of patients' quality of life. Imaging techniques such as US and MRI may be useful in the follow-up of pSS patients for prompt identification of AMs, for the quantification of their extent and ultimately for providing guidance on treatment and improving patient care.
33115760 Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELEC 2020 Oct 28 OBJECTIVES: This integrated analysis presents the safety profile of upadacitinib, a Janus kinase inhibitor, at 15 mg and 30 mg once daily in patients with moderately to severely active rheumatoid arthritis (RA). METHODS: Treatment-emergent adverse events (TEAEs) and laboratory data from five randomised, placebo- or active-controlled phase III trials of upadacitinib for patients with RA were analysed and summarised. Exposure-adjusted event rates are shown for placebo (three trials; 12/14 weeks), methotrexate (two trials; mean exposure: 36 weeks), adalimumab (one trial; mean exposure: 42 weeks), upadacitinib 15 mg (five trials; mean exposure: 53 weeks) and upadacitinib 30 mg (four trials; mean exposure: 59 weeks). RESULTS: 3834 patients received one or more doses of upadacitinib 15 mg (n=2630) or 30 mg (n=1204), for a total of 4020.1 patient-years of exposure. Upper respiratory tract infection, nasopharyngitis and urinary tract infection were the most commonly reported TEAEs with upadacitinib. Rates of serious infection were similar between upadacitinib 15 mg and adalimumab but higher compared with methotrexate. Rates of herpes zoster and creatine phosphokinase (CPK) elevations were higher in both upadacitinib groups versus methotrexate and adalimumab, and rates of gastrointestinal perforations were higher with upadacitinib 30 mg. Rates of deaths, malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs) were similar across treatment groups. CONCLUSION: In the phase III clinical programme for RA, patients receiving upadacitinib had an increased risk of herpes zoster and CPK elevation versus adalimumab. Rates of malignancies, MACEs and VTEs were similar among patients receiving upadacitinib, methotrexate or adalimumab. TRIAL REGISTRATION NUMBERS: SELECT-EARLY: NCT02706873; SELECT-NEXT: NCT02675426; SELECT-COMPARE: NCT02629159; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847.
32358157 Are Salivary Gland Ultrasonography Scores Associated with Salivary Flow Rates and Oral Hea 2020 Dec 1 OBJECTIVE: Major salivary gland ultrasonography (SGUS) is a widely used imaging technique to evaluate salivary gland involvement in primary Sjögren syndrome (pSS). The aim of this study was to evaluate the relationship between SGUS, salivary flow rate (SFR) as an objective measure of the gland function, and oral health-related quality of life (OHRQOL) as a patient-reported outcome measure (PROM) in a pSS cohort. METHODS: Sixty-six patients with pSS were examined by SGUS according to Hocevar and Milic scoring systems. Patients with inhomogeneity/hypoechoic areas with scores ≥ 2 in parotid and submandibular glands were classified separately as "severe glandular involvement." Further, oral health, SFR, and Oral Health Impact Profile-14 (OHIP-14) for OHRQOL were assessed. RESULTS: Both total Hocevar and Milic scores were higher in 21 pSS patients with low unstimulated whole salivary flow rate (U-WSFR) than 45 pSS patients without low U-WSFR (P = 0.001 and P < 0.0001, respectively). Increased scores of homogeneity, hypoechoic areas and glandular border visibility were observed in patients with low U-WSFR (P < 0.05). Among these variables, homogeneity score was found to be an independent risk factor for low U-WSFR in pSS according to logistic regression analysis (OR 1.586, P = 0.001). Moreover, a higher OHIP-14 score was observed in severe parotid involvement compared to nonsevere cases (23.26 ± 21.19 vs 8.32 ± 13.82, P = 0.004). CONCLUSION: High Milic and Hocevar SGUS scores are associated with reduced SFR and poor OHRQOL as a PROM. The inhomogeneity component of the SGUS score is associated with low U-WSFR and is an indicator of severely affected gland function.
32607949 The efficacy and mechanism for action of iguratimod in primary Sjögren's syndrome patient 2020 Nov PURPOSE: Primary Sjögren's syndrome (pSS) has been proven as a systemic autoimmune disorder (such as Sjogren's syndrome dry eye). This research aimed to evaluate potential treating effects of Iguratimod on pSS. METHODS: Fifty pSS patients were enrolled and randomly divided into Conventional group and Iguratimod group. Improvement in pSS was evaluated every 4 weeks. pSS disease activity was evaluated with European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI). Symptoms were evaluated by determining EULAR Sjögren's syndrome patient-reported index (ESSPRI), platelet (PLT), IgG and Schirmer I test. Peripheral blood B cell molecules (CD135, IgD, CD38, CD20) and human B cell-activating factor-receptor (BAFF-R) were analyzed with flow cytometry. RESULTS: After treating for 12-weeks, pSS patients in Iguratimod and Conventional group showed a significant decrease in disease activity (ESSPRI, ESSDAI, PLT, IgG and Schirmer I test) comparing with baselines. Patients' ESSPRI (2.92 ± 0.19) and disease activity of ESSDAI (4.32 ± 0.29), PLT (95.64 ± 1.86), IgG (13.0 ± 0.45) and Schirmer I test (4.67 ± 0.31) in Iguratimod group were significantly lower compared to Conventional group (4.64 ± 0.15, 5.8 ± 2.08, 77.44 ± 1.41, 16.5 ± 0.44 and 2.25 ± 0.11) (p < 0.0001). Changes of ESSPRI, ESSDAI, PLT, IgG and Schirmer I test were remarkable observed between two groups (p < 0.001). Iguratimod and Conventional treatment demonstrated a significant reduction in total B cells in pSS patients compared with pre-treatment. The pSS patients from Iguratimod and Conventional group showed a significant decreased BAFF-R (61.82 ± 1.52, 74.07 ± 1.11) and CD38(+)IgD(+) (48.08 ± 0.92, 62.66 ± 1.12) on B cells after treatment compared with baseline (92.26 ± 0.32, 91.53 ± 0.45, 84.39 ± 0.59, 85.04 ± 0.46) (p < 0.001). After treating 12 weeks, BAFF-R, CD38(+)IgD(+) expression in Iguratimod group decreased significantly compared to Conventional group (p < 0.001). CONCLUSIONS: Iguratimod alleviated symptoms and mediated adaptive-immunity balance by suppressing BAFF-R positive B cell in pSS patients.
32529559 Renal disorders in rheumatologic diseases: the spectrum is changing (Part 1: connective ti 2021 Aug The kidney is frequently involved by autoimmune rheumatic diseases. The renal manifestations may be variable, ranging from asymptomatic proteinuria and microscopic haematuria to nephrotic syndrome and rapidly progressive glomerulonephritis or vasculitis. In a number of cases the kidney involvement is related to the treatment of the original disease and may represent a major cause of morbidity and mortality. Thus, it is important for nephrologists and rheumatologists to remember that dysfunction of the kidney may be part of the primary systemic disorder or consequence of its pharmacotherapy. In the first part of this review we will analyse the kidney involvement in four autoimmune connective tissue diseases: systemic lupus erythematosus, Sjögren syndrome, polymyositis/dermatomyositis, and systemic sclerosis. Renal disease is common in lupus and is a main cause of morbidity and mortality. About 10% of patients with Sjögren syndrome may present interstitial nephritis or, more rarely, glomerulonephritis. Myoglobinuria and acute kidney injury is a frequent complication of polymyositis. Renal disease is one of the most serious complications of systemic sclerosis and may present with a dramatic renal crisis, characterized by malignant hypertension, oligo-anuria, and microangiopathic thrombocytopenic anaemia.
32418614 Primary Sjӧgren's syndrome with renal Fanconi syndrome: Good responses to treatment with 2020 Dec BACKGROUND: Renal Fanconi syndrome (FS) is rare in primary Sjӧgren's syndrome (pSS). We aimed to describe the clinicopathological characteristics of pSS associated FS (pSS-FS) and its responses to treatment. METHODS: We reported 25 cases of pSS-FS patients and retrospectively reviewed their clinical records, kidney pathology and follow-up data. RESULTS: The 25 pSS-FS patients were mainly female (92.0%) and the mean age at diagnosis was 43.6±11.3 years. They showed different degrees of proximal tubular dysfunctions and eGFR decline (60.9±32.3 ml/min/1.73m(2)). Kidney pathology of pSS-FS patients showed tubulo-interstitial nephritis with defective brush border and lymphoplasmacytic infiltrates. After glucocorticoid treatment, the eGFR levels were significantly improved from 48.3±20.6 ml/min/1.73m(2) to 55.0±19.9 ml/min/1.73m(2) (P = 0.012) at the third month of follow-up. They also acquired good tubular (88.2%) and immunological (90.0%) responses. pSS-FS patients with young-onset pSS presented with a higher prevalence of positive anti-SSB antibody and hypocomplementemia, more severe hypokalemia, and better eGFR levels. CONCLUSIONS: In pSS-FS patients, use of glucocorticoids could improve eGFR and tubular functions. The young-onset pSS group presented with a particular pattern in immunological features and kidney involvement.
32713853 Fangchinoline Has an Anti-Arthritic Effect in Two Animal Models and in IL-1β-Stimulated H 2020 Sep 1 Fangchinoline (FAN) is a bisbenzylisoquinoline alkaloid that is widely known for its anti-tumor properties. The goal of this study is to examine the effects of FAN on arthritis and the possible pathways it acts on. Human fibroblast-like synovial cells (FLS), carrageenan/ kaolin arthritis rat model (C/K), and collagen-induced arthritis (CIA) mice model were used to establish the efficiency of FAN in arthritis. Human FLS cells were treated with FAN (1, 2.5, 5, 10 μM) 1 h before IL-1β (10 ng/mL) stimulation. Cell viability, reactive oxygen species measurement, and western blot analysis of inflammatory mediators and the MAPK and NF-κB pathways were performed. In the animal models, after induction of arthritis, the rodents were given 10 and 30 mg/kg of FAN orally 1 h before conducting behavioral experiments such as weight distribution ratio, knee thickness measurement, squeaking score, body weight measurement, paw volume measurement, and arthritis index measurement. Rodent knee joints were also analyzed histologically through H&E staining and safranin staining. FAN decreased the production of inflammatory cytokines and ROS in human FLS cells as well as the phosphorylation of the MAPK pathway and NF-κB pathway in human FLS cells. The behavioral parameters in the C/K rat model and CIA mouse model and inflammatory signs in the histological analysis were found to be ameliorated in FAN-treated groups. Cartilage degradation in CIA mice knee joints were shown to have been suppressed by FAN. These findings suggest that fangchinoline has the potential to be a therapeutic source for the treatment of rheumatoid arthritis.
33081234 Antioxidant Carbon Nanoparticles Inhibit Fibroblast-Like Synoviocyte Invasiveness and Redu 2020 Oct 16 Reactive oxygen species have been involved in the pathogenesis of rheumatoid arthritis (RA). Our goal was to determine the effects of selectively scavenging superoxide (O(2)(•-)) and hydroxyl radicals with antioxidant nanoparticles, called poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), on the pathogenic functions of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and on the progression of an animal model of RA. We used human FLS from patients with RA to determine PEG-HCC internalization and effects on FLS cytotoxicity, invasiveness, proliferation, and production of proteases. We used the pristane-induced arthritis (PIA) rat model of RA to assess the benefits of PEG-HCCs on reducing disease severity. PEG-HCCs were internalized by RA-FLS, reduced their intracellular O(2)(•-), and reduced multiple measures of their pathogenicity in vitro, including proliferation and invasion. In PIA, PEG-HCCs caused a 65% reduction in disease severity, as measured by a standardized scoring system of paw inflammation and caused a significant reduction in bone and tissue damage, and circulating rheumatoid factor. PEG-HCCs did not induce lymphopenia during PIA. Our study demonstrated a role for O(2)(•-) and hydroxyl radicals in the pathogenesis of a rat model of RA and showed efficacy of PEG-HCCs in treating a rat model of RA.
32794262 Immature neutrophil signature associated with the sexual dimorphism of systemic juvenile i 2020 Oct Juvenile idiopathic arthritis (JIA) is a group of inflammatory conditions of unknown etiology whose incidence is sex dependent. Although several studies have attempted to identify JIA-related gene signatures, none have systematically assessed the impact of sex on the whole blood transcriptomes of JIA patients. By analyzing over 400 unique pediatric gene expression profiles, we characterized the sexual differences in leukocyte composition of systemic JIA patients and identified sex-specific gene signatures that were related to immature neutrophils. Female systemic JIA patients presented higher activation of immature neutrophil-related genes compared to males, and these genes were associated with the response to IL-1 receptor blockade treatment. Also, we found that this immature neutrophil signature is sexually dimorphic across human lifespan and in adults with rheumatoid arthritis and asthma. These results suggest that neutrophil maturation is sexually dimorphic in rheumatic inflammation, and that this may impact disease progression and treatment.
32884773 Novel homozygous variant in WISP3 in a family with unrecognized progressive pseudorheumato 2020 Aug We present the use of whole-genome sequencing to correctly diagnose progressive pseudorheumatoid dysplasia in patients with atypical clinical and radiologic findings and prior diagnosis of juvenile idiopathic arthritis.
32817908 Peripheral mechanisms of arthritic pain: A proposal to leverage large animals for in vitro 2020 Aug Pain arising from musculoskeletal disorders such as arthritis is one of the leading causes of disability. Whereas the past 20-years has seen an increase in targeted therapies for rheumatoid arthritis (RA), other arthritis conditions, especially osteoarthritis, remain poorly treated. Although modulation of central pain pathways occurs in chronic arthritis, multiple lines of evidence indicate that peripherally driven pain is important in arthritic pain. To understand the peripheral mechanisms of arthritic pain, various in vitro and in vivo models have been developed, largely in rodents. Although rodent models provide numerous advantages for studying arthritis pathogenesis and treatment, the anatomy and biomechanics of rodent joints differ considerably to those of humans. By contrast, the anatomy and biomechanics of joints in larger animals, such as dogs, show greater similarity to human joints and thus studying them can provide novel insight for arthritis research. The purpose of this article is firstly to review models of arthritis and behavioral outcomes commonly used in large animals. Secondly, we review the existing in vitro models and assays used to study arthritic pain, primarily in rodents, and discuss the potential for adopting these strategies, as well as likely limitations, in large animals. We believe that exploring peripheral mechanisms of arthritic pain in vitro in large animals has the potential to reduce the veterinary burden of arthritis in commonly afflicted species like dogs, as well as to improve translatability of pain research into the clinic.