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ID PMID Title PublicationDate abstract
32458203 Correction to: Comparative Effectiveness of Combining MTX with Biologic Drug Therapy Versu 2020 May 26 This article has been amended to include open access.
32569446 Can artificial intelligence identify effective COVID-19 therapies? 2020 Aug 7 In this issue of EMBO Molecular Medicine, Stebbing et al (2020b) validate an artificial intelligence-assisted prediction that a drug used to treat rheumatoid arthritis could be a potent weapon against COVID-19. Using liver organoids infected with SARS-CoV-2, they confirm dual antiviral and anti-inflammatory activities and show that its administration in four COVID-19 patients is correlated with disease improvement, paving the way for more rigorous placebo-controlled trials.
32128039 The salivary microbiota in health and disease. 2020 The salivary microbiota (SM), comprising bacteria shed from oral surfaces, has been shown to be individualized, temporally stable and influenced by diet and lifestyle. SM reflects local bacterial alterations of the supragingival and subgingival microbiota, and periodontitis and dental-caries associated characteristics of SM have been reported. Also, data suggest an impact of systemic diseases on SM as demonstrated in patients with a wide variety of systemic diseases including diabetes, cancer, HIV and rheumatoid arthritis. The presence of systemic diseases seems to influence salivary levels of specific bacterial species, as well as α- and β-diversity of SM. The composition of SM might thereby potentially mirror oral and general health status. The contentious development of advanced molecular techniques such as metagenomics, metatranscriptomics and metabolomics has enabled the possibility to address bacterial functions rather than presence in microbial samples. However, at present only a few studies have employed such techniques on SM to reveal functional and metabolic characteristics in oral health and disease. Future studies are therefore warranted to illuminate the possible impact of metabolic functions of SM on oral and general health status. Ultimately, such an approach has the possibility to reveal novel and personalized therapeutic avenues in oral and general medicine.
32063021 Mimickers of Hill-Sachs Lesions [Formula: see text]. 2021 May The purpose of this article is to describe the imaging appearance, etiology, clinical features, and treatment of rare presentations of common bone and joint diseases known to mimic Hill-Sachs lesions. Knowledge of uncommonly encountered manifestations of ankylosing spondylitis, rheumatoid arthritis, septic joint, hyperparathyroidism, hydroxyapatite deposition disease, malignant bone tumors, and benign bone cysts which mimic traumatic Hill-Sachs lesions is important for radiologists to guide the clinical care of patients who present with shoulder symptoms.
31978952 Insights on the Effects of Resveratrol and Some of Its Derivatives in Cancer and Autoimmun 2020 Jan 22 In recent years, the interest in natural compounds exerting immunoregulatory effects has enormously increased. Among these, the polyphenol resveratrol, found in a variety of foods and beverages, including red grapes and red wine, has been demonstrated to exert both in vitro and in vivo biological activities. More specifically, it has antiaging, cardioprotective, antioxidant, immunomodulatory, anti-inflammatory and chemopreventive activities. Due to its anti-proliferative, pro-apoptotic and immunoregulatory effects, resveratrol has gained substantial attention for the treatment of cancer or autoimmunity, which represent frequently diagnosed diseases with important consequences for the health of the patients affected. The aim of the present review is to focus on the role of resveratrol in the modulation of cancer as well as of several organ-specific or systemic autoimmune diseases, including autoimmune hepatitis, type 1 diabetes mellitus, inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis.
32966190 Impact of anti-citrullinated protein antibody on tumor necrosis factor inhibitor or abatac 2020 Sep 18 OBJECTIVE: To assess the impact of anti-citrullinated protein antibody (ACPA) serostatus on response to treatment with either tumor necrosis factor inhibitors (TNFi) or abatacept in patients with rheumatoid arthritis (RA). METHODS: Data was obtained from the Optimizing Patient outcomes in Australian RheumatoLogy (OPAL) dataset. Patient data were included in the analysis if they commenced treatment with abatacept or TNFi between 01 August 2006 and 30 June 2017 and had at least 12 months' follow-up. The primary outcome was the mean change in the clinical disease activity index (CDAI) score from baseline to 12 months. RESULTS: A total of 2,052 patients were included of which 1,415 were in the TNFi cohort (n=1,053 ACPA positive) and 637 in the abatacept cohort (n=445 ACPA positive). Patients were predominantly female (75% TNFi; 80% abatacept) with no significant difference in age between cohorts. Patients with ACPA positivity had longer disease duration before commencing treatment in both the TNFi and abatacept cohorts compared to ACPA negative patients. No difference in disease severity was observed in those with ACPA negativity compared to those with ACPA positivity. Patients treated with TNFi and abatacept had significantly improved mean change in CDAI after 12 months; ACPA positivity was associated with greater response to treatment with abatacept compared to that in patients with ACPA negativity (p=0.011). No difference in response was observed based on ACPA serostatus in patients treated with TNFi (p=0.73). CONCLUSION: Baseline ACPA positivity was associated with improved clinical response using CDAI outcome measure at 12 months for abatacept but not for TNFi therapies.
32923679 C-C chemokine receptor type 5 links COVID-19, rheumatoid arthritis, and Hydroxychloroquine 2020 Patients with rheumatoid arthritis (RA) represent one of the fragile patient groups that might be susceptible to the critical form of the coronavirus disease - 19 (COVID-19). On the other side, RA patients have been found not to have an increased risk of COVID-19 infection. Moreover, some of the Disease-Modifying Anti-Rheumatic Drugs (DMARDS) commonly used to treat rheumatic diseases like Hydroxychloroquine (HCQ) were proposed as a potential therapy for COVID-19 with a lack of full understanding of their molecular mechanisms. This highlights the need for the discovery of common pathways that may link both diseases at the molecular side. In this research, we used the in silico approach to investigate the transcriptomic profile of RA synovium to identify shared molecular pathways with that of severe acute respiratory syndrome-corona virus-2 (SARS-COV-2) infected lung tissue. Our results showed upregulation of chemotactic factors, including CCL4, CCL8, and CCL11, that all shared CCR5 as their receptor, as a common derangement observed in both diseases; RA and COVID-19. Moreover, our results also highlighted a possible mechanism through which HCQ, which can be used as a monotherapy in mild RA or as one of the triple-DMARDs therapy (tDMARDs; methotrexate, sulphasalazine, and HCQ), might interfere with the COVID-19 infection. This might be achieved through the ability of HCQ to upregulate specific immune cell populations like activated natural killer (NK) cells, which were found to be significantly reduced in COVID-19 infection. In addition to its ability to block CCR5 rich immune cell recruitment that also was upregulated in the SARS-COV-2 infected lungs. This might explain some of the reports that showed beneficial effects.
32445935 Prevalence of COVID-19 among patients with chronic inflammatory rheumatic diseases treated 2020 Oct OBJECTIVE: The aim of this study is to determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) among adult patients treated with biologic agents or small molecules for chronic inflammatory rheumatic diseases, in particular for chronic inflammatory arthritides. METHODS: To this end, a population-based study, in the province of Udine (466,700 inhabitants, with age>15 years old, Friuli Venezia Giulia region, Italy) was planned. The primary outcome was the prevalence of COVID-19 in the first two months of the outbreak. All the rheumatic patients treated with biologic agents or small molecules in the last 6 months in our province were included (N=1051). RESULTS: From February 29 to April 25, 2020, 4 adult patients (4/1051, i.e. 3.8/1000, 95% Confidence Interval 1.5-9.7/1000) were registered as swab test positive by PCR for COVID-19. Overall, a total of 47/1051 (4.5%) cases were tested for COVID-19 by PCR in the same period, and 15 of them due to symptoms compatible with COVID-19. In the general population, the prevalence was 937 cases/466700 (2/1000, 95% Confidence Interval 1.9-2.1/1000, P-value=0.33, chi square test), and 20,179/466,700 (4.3%) swab tests for COVID-19 were performed. CONCLUSION: The risk of COVID-19 in rheumatic patients under biologic agents or small molecules does not appear different from that observed in the general population. Patients should be informed to safely proceed with their treatment and follow the rules for self-protection to COVID-19.
32012969 Impact of Varied Factors on Iron, Nickel, Molybdenum and Vanadium Concentrations in the Kn 2020 Jan 28 The aim of this study was to determine the concentrations of iron, nickel, molybdenum, and vanadium in the knee joint. We also examined the relationships between the concentrations of these metals in the knee joint and the influence of varied factors on the concentration of Fe, Ni, Mo, and V. The study of these trace elements is important, because these elements are used alone and in combination in diet supplements, and they are components of biomaterials implanted in medicine. The study materials, consisting of the spongy bone, cartilage, meniscus, anterior cruciate ligament (ACL), and infrapatellar fat pad, were obtained from 34 women and 12 men from northwestern Poland. The concentrations of Ni, Fe, Mo, and V were determined using spectrophotometric atomic absorption in inductively coupled argon plasma (ICP-AES). We found significantly higher Mo concentrations in the ACL of women than men. There was a significant difference in the Mo concentration in the spongy bone between patients from cities with fewer than 100,000 inhabitants and patients from cities with more than 100,000 residents. Iron concentrations in the spongy bone were higher in non-smoking patients and those who did not consume alcohol. Vanadium concentrations were higher in the infrapatellar fat pads in abstainers. In patients who had not undergone arthroscopy surgery, V concentration was lower in cartilage. The concentrations of V in the cartilage and infrapatellar fat pad were higher in osteoporotic patients than in non-osteoporotic patients. There were significant differences in Fe concentrations in the meniscus, with the lowest in osteoporotic patients. We noted lower Mo concentrations in the spongy bone of patients with rheumatoid arthritis. Furthermore, we noted some new interactions among metals in the studied structures of the knee joint. The results reported in this study show the influence of gender, place of residence, smoking, consumption of alcohol, arthroscopy surgery, osteoporosis, and rheumatoid arthritis on the Fe, Ni, Mo, and V concentrations in the studied structures of the knee joint.
32963045 Unique expansion of IL-21+ Tfh and Tph cells under control of ICOS identifies Sjögren's s 2020 Dec OBJECTIVES: To explore the relevance of T-follicular-helper (Tfh) and pathogenic peripheral-helper T-cells (Tph) in promoting ectopic lymphoid structures (ELS) and B-cell mucosa-associated lymphoid tissue (MALT) lymphomas (MALT-L) in Sjögren's syndrome (SS) patients. METHODS: Salivary gland (SG) biopsies with matched peripheral blood were collected from four centres across the European Union. Transcriptomic (microarray and quantitative PCR) analysis, FACS T-cell immunophenotyping with intracellular cytokine detection, multicolor immune-fluorescence microscopy and in situ hybridisation were performed to characterise lesional and circulating Tfh and Tph-cells. SG-organ cultures were used to investigate functionally the blockade of T-cell costimulatory pathways on key proinflammatory cytokine production. RESULTS: Transcriptomic analysis in SG identified Tfh-signature, interleukin-21 (IL-21) and the inducible T-cell co-stimulator (ICOS) costimulatory pathway as the most upregulated genes in ELS+SS patients, with parotid MALT-L displaying a 400-folds increase in IL-21 mRNA. Peripheral CD4(+)CXC-motif chemokine receptor 5 (CXCR5)(+)programmed cell death protein 1 (PD1)(+)ICOS(+) Tfh-like cells were significantly expanded in ELS+SS patients, were the main producers of IL-21, and closely correlated with circulating IgG and reduced complement C4. In the SG, lesional CD4(+)CD45RO(+)ICOS(+)PD1(+) cells selectively infiltrated ELS+ tissues and were aberrantly expanded in parotid MALT-L. In ELS+SG and MALT-L parotids, conventional CXCR5(+)CD4(+)PD1(+)ICOS(+)Foxp3(-) Tfh-cells and a uniquely expanded population of CXCR5(-)CD4(+)PD1(hi)ICOS(+)Foxp3(-) Tph-cells displayed frequent IL-21/interferon-γ double-production but poor IL-17 expression. Finally, ICOS blockade in ex vivo SG-organ cultures significantly reduced the production of IL-21 and inflammatory cytokines IL-6, IL-8 and tumour necrosis factor-α (TNF-α). CONCLUSIONS: Overall, these findings highlight Tfh and Tph-cells, IL-21 and the ICOS costimulatory pathway as key pathogenic players in SS immunopathology and exploitable therapeutic targets in SS.
32499649 Complement genes contribute sex-biased vulnerability in diverse disorders. 2020 Jun Many common illnesses, for reasons that have not been identified, differentially affect men and women. For instance, the autoimmune diseases systemic lupus erythematosus (SLE) and Sjögren's syndrome affect nine times more women than men(1), whereas schizophrenia affects men with greater frequency and severity relative to women(2). All three illnesses have their strongest common genetic associations in the major histocompatibility complex (MHC) locus, an association that in SLE and Sjögren's syndrome has long been thought to arise from alleles of the human leukocyte antigen (HLA) genes at that locus(3-6). Here we show that variation of the complement component 4 (C4) genes C4A and C4B, which are also at the MHC locus and have been linked to increased risk for schizophrenia(7), generates 7-fold variation in risk for SLE and 16-fold variation in risk for Sjögren's syndrome among individuals with common C4 genotypes, with C4A protecting more strongly than C4B in both illnesses. The same alleles that increase risk for schizophrenia greatly reduce risk for SLE and Sjögren's syndrome. In all three illnesses, C4 alleles act more strongly in men than in women: common combinations of C4A and C4B generated 14-fold variation in risk for SLE, 31-fold variation in risk for Sjögren's syndrome, and 1.7-fold variation in schizophrenia risk among men (versus 6-fold, 15-fold and 1.26-fold variation in risk among women, respectively). At a protein level, both C4 and its effector C3 were present at higher levels in cerebrospinal fluid and plasma(8,9) in men than in women among adults aged between 20 and 50 years, corresponding to the ages of differential disease vulnerability. Sex differences in complement protein levels may help to explain the more potent effects of C4 alleles in men, women's greater risk of SLE and Sjögren's syndrome and men's greater vulnerability to schizophrenia. These results implicate the complement system as a source of sexual dimorphism in vulnerability to diverse illnesses.
32161138 Suppression of age-related salivary gland autoimmunity by glycosylation-dependent galectin 2020 Mar 24 Aging elicits quantitative and qualitative changes in different immune components, leading to disruption of tolerogenic circuits and development of autoimmune disorders. Galectin-1 (Gal1), an endogenous glycan-binding protein, has emerged as a regulator of immune cell homeostasis by shaping the fate of myeloid and lymphoid cells. Here, we demonstrate that aged Gal1-null mutant (Lgals1 (-/-) ) mice develop a spontaneous inflammatory process in salivary glands that resembles Sjögren's syndrome. This spontaneous autoimmune phenotype was recapitulated in mice lacking β1,6N-acetylglucosaminyltransferase V (Mgat5), an enzyme responsible for generating β1,6-branched complex N-glycans, which serve as a major ligand for this lectin. Lack of Gal1 resulted in CD11c(+) dendritic cells (DCs) with higher immunogenic potential, lower frequency of Foxp3(+) regulatory T cells (Tregs), and increased number of CD8(+) T cells with greater effector capacity. Supporting its tolerogenic activity, Gal1 expression decreased with age in autoimmunity-prone nonobese diabetic (NOD) mice. Treatment with recombinant Gal1 restored tolerogenic mechanisms and reduced salivary gland inflammation. Accordingly, labial biopsies from primary Sjögren's syndrome patients showed reduced Gal1 expression concomitant with higher number of infiltrating CD8(+) T cells. Thus, endogenous Gal1 serves as a homeostatic rheostat that safeguards immune tolerance and prevents age-dependent development of spontaneous autoimmunity.
33164740 Positive effect of hydroxychloroquine on lipid profiles of patients with rheumatoid arthri 2020 Nov 5 OBJECTIVE: Despite remarkable improvements in rheumatoid arthritis (RA) treatment, there is evidence indicating that the mortality gap between patients with RA and the general population is not closing. The increase in mortality rates in patients with RA is predominantly due to cardiovascular disease (CVD). Literature suggests that important links exist between RA inflammation and atherosclerosis in CVD. Dyslipidemia is a well-known risk factor of atherosclerosis. Previous studies have suggested that antimalarials, chloroquine diphosphate, and hydroxychloroquine (HCQ), used in the treatment of autoimmune diseases, have a beneficial effect on the lipid levels. However, the studies had small sample sizes. We analyzed a Veterans Affair RA cohort of 2,925 patients to characterize the effect of 4 months' use of HCQ on the lipid levels. METHODS: Data for this cohort were obtained from the department of Veterans Affairs administrative database. Individuals (age ≥18 years) with a diagnosis of RA (ICD-9 code) at 2 or more outpatient visits from 1999 to 2009 were identified. Only the patients with at least 1 lipid level measured at 120-180 days before staring HCQ were included. Lipids levels on pre- and poststart dates of HCQ (120-180 days) were compared using student's t-test and adjusted for age, sex, race, C-reactive protein (CRP), and statin use with multivariable regression (analysis of variance/analysis of covariance) for the change in different lipid levels. To give equal weightage to covariables, we conducted an analysis of marginal means for race in each lipid level. All analyses were performed using STATA 11. RESULTS: After adjusting for sex, age, race, statin use, and post CRP values >10 mg/dL using a linear regression, the factor driving the change in the different lipid levels was race (p values for total cholesterol, 0.006; low-density lipoprotein, 0.09; non-high-density lipoprotein [HDL], 0.03; atherogenic index, 0.08; and HDL, 0.17). When considering race individually using marginal means analysis, the race in the subgroup "others" was more influential. CONCLUSION: Our results suggest that sex and race influences the HCQ effect on the lipid profiles in patients with RA. Use of HCQ in males is found to be associated with positive changes in the lipid profiles independent from the use of statins. There is a suggestion that whites and African Americans might be less susceptible to HCQ effect on lipid profiles than other races.
32963566 Effect of Moxibustion on Inflammatory Cytokines in Animals with Rheumatoid Arthritis: A Sy 2020 BACKGROUND: This study aims to systematically evaluate the effect of moxibustion on the level of inflammatory cytokines in animal models with rheumatoid arthritis (RA) and to provide evidence for the clinical application of moxibustion to the treatment of RA and related basic researches. METHODS: The databases employed in this study include PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), SinoMed, and Wanfang Data Information Site. The retrieval time was from the establishment of these databases to March 2020. The reviewers made use of the CAMARADES 10-item checklist to evaluate the quality of each included study. The inflammatory cytokines were considered as the outcome measure. The Revman 5.3 software was used to conduct meta-analysis on the outcome indicators of the studies included. RESULTS: A total of 648 articles were retrieved and 18 animal experiments were included in this study. The quality scores of the studies ranged from two to eight with a mean of 5.8. Compared with the effect of the control group, moxibustion reduced the expression of TNF-α (SMD 2.95, 95% CI: 1.99-3.92, P < 0.00001), IL-1β (SMD 4.10, 95% CI: 2.37-5.84, P < 0.00001), IFN-γ (MD 25, 95% CI: 16.17-33.82, P < 0.00001), IL-6 (MD 11.83, 95% CI: 6.22-17.44, P < 0.0001), and IL-17 (MD 99.3, 95% CI: 86.83-111.76, P < 0.00001). At the same time, the level of IL-2 (SMD 8.89, 95% CI: 0.93-16.86, P=0.03), IL-4 (MD 1.79, 95% CI: 0.26-3.32, P=0.02), and IL-10 (MD 5.93, 95% CI: 1.37-10.49, P=0.01) increased after moxibustion treatment. Asymmetric funnel plots indicated that there was publication bias. CONCLUSION: The findings of the present review indicate that moxibustion can protect the synovium of joint in animal models with RA by upregulation of the level of anti-inflammatory cytokines and downregulation of the level of proinflammatory cytokines. Moxibustion has the potential to relieve inflammation of RA.
32314534 Patient Perception of Cardiovascular Risk in Rheumatoid Arthritis. 2020 May OBJECTIVE: Patients with rheumatoid arthritis (RA) have higher incidence of cardiovascular diseases (CVDs) compared with age- and sex-matched controls. The objective of our study was to measure the knowledge of patients with RA about the association between their disease and cardiovascular (CV) risk and to measure the frequency of counseling by physicians based on patient report. METHODS: A telephone survey was conducted among patients with RA enrolled in the Consortium of Rheumatology Researchers of North America RA registry to collect data on medical and social history and on knowledge about CVD risk in RA and how they learned about that risk. Multivariable logistic regression models were performed to determine the factors associated with patients' knowledge and factors influencing likelihood of physician counseling. The odds ratios (ORs) represent adjusted multivariable results. RESULTS: Of 185 patients with RA included in the study, 87 patients (47%) were aware that RA was a CV risk factor. Older age (OR 0.6; 95% confidence interval [CI] 0.4-0.8 per decade) and smoking (OR 0.4; 95% CI 0.1-0.9) were associated with low awareness, whereas disease duration of more than 10 years (OR 5.2; 95% CI 2.2-12.1) was positively associated with patient knowledge. Counseling by physicians, mostly rheumatologists, on CV risk in RA was reported by 47 patients (25%). Disease duration of more than 10 years (OR 3.9; 95% CI 1.2-13.1) was positively associated with patient-reported counseling. Patients with hypertension were less likely to report counseling (OR 0.4; 95% CI 0.2-0.9). CONCLUSION: Our study demonstrated low patient awareness of CV risk with RA and low rates of patient-reported counseling by physicians. This is an unmet need in clinical practice, which may be overcome by multimodal approaches such as developing websites, organizing symposiums, and involving health care providers at various levels.
33301910 Comprehensive evaluation on anti-inflammatory and anti-angiogenic activities in vitro of f 2021 Mar 25 ETHNOPHARMACOLOGICAL RELEVANCE: Genkwa flos, as a traditional herb, is the dried flower buds of Daphne genkwa Sieb.et Zucc. It is used in traditional medicine for the treatment of cough, sore throats, edema. AIM OF THE STUDY: The study aimed to explore a new mathematical method for multivariate evaluation, investigate the anti-inflammatory and anti-angiogenic activities of flavonoids in Daphne Genkwa under ex vivo conditions. MATERIALS AND METHODS: The flavonoids monomers in Daphne Genkwa were separated by preparative liquid chromatography and identified by HPLC-ESI-ITMS. An in vitro inflammatory model of macrophage RAW264.7 induced by LPS and an angiogenesis model of human umbilical vein endothelial cells induced by TNF-α were established. Flavonoids were extracted and prepared for intervention to detect the amount of secretion after drug intervention to reflect the anti-inflammatory and anti-angiogenic activities of each component. In addition, a new mathematical method, which combined principal component analysis and efficacy coefficient method, was adopted in pharmacodynamic evaluation. RESULTS: Fourteen flavonoids monomers were separated by preparative liquid chromatography and identified by HPLC-ESI-ITMS including H1 (hydroxygenkwanin-5-O-β-D-glucoside), H2 (apigenin-7-O-β-D-glucoside), H3 (kaempferol-3-O-β-D-glucoside), H4 (hydroxygenkwanin-5-O-β-D-primeveroside), H5 (apigenin-5-O-β-D-primeveroside), H6 (apigenin-7-O-β-D-glucuronide), H7 (luteolin-5-O-β-D-glucopyranoside), H8 (genkwain-5-O-β-D- glucoside), H9 (luteolin), H10 (Daphnodorin G), H11 (tiliroside), H12 (apigenin), H13 (3'- hydroxygenkwain) and H14 (genkwanin). We found that most of flavonoids down-regulated VCAM and MMP-3, while H1, H8, H9, H14 reduced VEGF and ICAM was only decreased by H14. CONCLUSION: Genkwanin may be the most active anti-rheumatoid arthritis flavonoids in Daphne genkwa. Meanwhile, the new mathematical method used in the study provided a new direction for solving the problem of multi-index pharmacodynamic evaluation.
33259751 Clinical features and outcomes from the Singapore Sjögren's syndrome study. 2021 Feb OBJECTIVE: To study the clinical features, treatment and outcomes of primary Sjögren's Syndrome (pSS) in a Singapore cohort from an outpatient rheumatology clinic. METHODS: Computerised Physician Order entry records of patients who fulfilled the 2016 ACR-EULAR classification criteria for pSS between 1993 and 2013 were retrospectively analysed. RESULTS: There were 102 patients, of which 96 (94.1%) were females, and 91 (89.2%) Chinese. Mean age at diagnosis was 49.3 ± 11.8 years, mean disease duration was 9.0 ± 4.6 years. The most common manifestations were keratoconjunctivitis sicca (99.0%), xerostomia (96.1%), arthralgia/arthritis (56.9%). Exocrine glandular enlargement comprised parotidomegaly (28, 27.5%), with concurrent submandibular and lacrimal gland enlargement in one. The nervous system (15.7%) was the most commonly affected internal organ, with peripheral nervous system (peripheral neuropathy, mononeuritis multiplex) involvement more common than central. Hydroxychloroquine was most frequently used (88.2%), followed by methotrexate (7.8%) and azathioprine (6.9%). Pulsed intravenous (IV) methylprednisolone 500 mg/day for 3 days was used in 5 patients followed by oral (4) or IV cyclophosphamide (1) for cardiomyopathy and interstitial lung disease (1), and neurological involvement (4). These comprised neuromyelitis optica, transverse myelopathy, cranial neuropathy, mononeuritis multiplex and/or peripheral neuropathy alone or in combination. Intravenous immunoglobulins (2.0%) was used for sensory neuropathy and mononeuritis multiplex; rituximab (1.0%) in 1 patient for treatment of non-Hodgkin's B-cell lymphoma. There were no deaths. CONCLUSION: Musculoskeletal manifestations were common, with the nervous system (peripheral more than central) the most common internal organ involved. Lymphoma was uncommon despite up to one-third of the cohort developing glandular enlargement.
33086170 Artesunate inhibits Sjögren's syndrome-like autoimmune responses and BAFF-induced B cell 2021 Jan BACKGROUND: Hyperactivation of B cells by activators has been demonstrated to play a central role in the pathogenesis of Sjögren's syndrome (SS). In this study, we found that artesunate (ART) can attenuate BAFF-induced B cell hyperactivation and SS-like symptoms in NOD/Ltj mice. PURPOSE: To determine the efficacy of ART in attenuating SS-like symptoms in vivo and explore the underlying mechanism in vitro. STUDY DESIGN: ART was intragastrically injected into SS-like NOD/Ltj mice. The cytokine hsBAFF was used to activate Raji and Daudi B cells to mimic B cell hyperactivation in vitro. METHODS: The efficacy of ART in inhibiting SS progression was studied in NOD/Ltj mice. Salivary flow rate, the number of lymphocytic infiltration foci, the level of autoantibodies and the extent of B cell infiltration were measured in the indicated groups. CCK-8 assays, flow cytometry-based EdU staining and Annexin V/PI staining were also used to detect the effect of ART on the survival and proliferation mechanism in BAFF-induced Raji and Daudi cells. Further studies determined that TRAF6 degradation is a potential mechanism by which ART determines B cell fate. RESULTS: Treatment with ART inhibited lymphocytic foci formation, B cell infiltration and autoantibody secretion in SS-like NOD/Ltj mice. In vitro assay results indicated that ART effectively inhibited BAFF-induced viability, survival and proliferation of neoplastic B cells. Mechanistically, ART targeted BAFF-activated NFκB by regulating the proteasome-mediated degradation of TRAF6 in Raji and Daudi cells. CONCLUSION: ART ameliorated murine SS-like symptoms and regulated TRAF6-NFκB signaling, thus determining survival and proliferation of B cells.
32029330 Correction of autophagy impairment inhibits pathology in the NOD.H-2h4 mouse model of prim 2020 Mar Dysregulation of autophagy has been implicated in the development of various disease indications including autoimmune diseases. Here we identified hitherto unsuspected molecular alterations of autophagy occurring at an early stage of the macroautophagy pathway in the salivary glands and spleen of NOD.H-2h4 mice that develop a primary Sjögren's-like syndrome. In this study we investigated the capacity of phosphopeptide P140 to correct immune alteration in NOD.H-2h4 mice and the effect on neogenesis of tertiary lymphoid structures in salivary glands, which is hallmark characteristic of SS. Phosphopeptide P140 known to lower excessive autophagy processes, rescued sick NOD.H-2h4 mice from some autophagy defects and significantly reduced formation of tertiary lymphoid structures in salivary glands. Mechanistically, the frequency of activated CD44(high)/CD62L(low) CD4(+) T cell populations was significantly decreased and this reduction was correlated with an increased number of CD44(low)/CD62L(high) resting T cells. The CD8 T cell compartment was not affected. P140 down-regulated the maturation and differentiation of B cells into plasma cells, and decreased IgG and autoantibody secretion. It had no effect on germinal centers B cells (B220(+) FAS(+)GL-7(+)) that are an important compound of the B cell humoral immune response. Together with previous data generated in MRL/lpr mice that develop some features of Sjögren's syndrome associated to other inflammatory and autoimmune defects, our present findings strongly reinforce the potential of autophagy modulators, such as P140, for treating patients with Sjögren's syndrome.
33292771 A feasibility study on two tailored interventions to improve adherence in adults with haem 2020 Dec 1 INTRODUCTION: Haemophilia is a congenital bleeding disorder mainly affecting males. To prevent bleeding, patients need to perform regular intravenous injections (prophylaxis) throughout life. Non-adherence often occurs. Problems with acceptance or self-management appear to be the main reasons for non-adherence in haemophilia. The aim of this study was to test the feasibility and effects of two interventions focussed on acceptance (face-to-face) and self-management (online). METHODS: Patients with severe haemophilia and acceptance or self-management problems were eligible. The face-to-face group intervention was based on Acceptance and Commitment Therapy (ACT) (8 sessions/6 months, target N = 8 participants). The online intervention was based on a successful online programme in rheumatoid arthritis (5-8 modules/2 months, target N = 8). Both interventions were designed according to the MRC framework in collaboration with the patient society and experts. We compared adherence (VERITAS-Pro, optimum 0), quality of life (SF-36, optimum 100) and illness perception (BIPQ, optimum 0) before start (T0) and after 2 months (T2). Feasibility criteria were as follows: completion of training by > 50% of participants and ability to collect at least 80% of outcome parameters. RESULTS: The face-to-face intervention was feasible (89% enrolment and recruitment, 100% retention). One hundred percent of the outcome parameters was collected. Results were promising: although adherence (VERITAS-Pro) was stable (from 64 to 62 points), quality of life (SF-36) showed a clinically relevant improvement (> 5 points) in five of eight domains. Illness perception (BIPQ) showed a clinically relevant increase from 47 to 39 points. Patient evaluation was positive. The online intervention, however, was infeasible: enrolment was only 20% (6/30). Only three patients signed informed consent (recruitment 10%), and none completed more than one module (retention 0%). Consequently, the online intervention was terminated. CONCLUSION: The face-to-face acceptance intervention was considered feasible with promising results. Unfortunately, the online intervention was infeasible and therefore terminated. These findings suggest that adapting effective interventions to other settings does not guarantee success, despite the use of established methodology and patient participation. Population differences (only male participants, congenital disease) could be an explanation for failure of the online intervention in haemophilia despite success in rheumatoid arthritis. TRIAL REGISTRATION: NL55883.041.16.