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ID PMID Title PublicationDate abstract
30871871 Apoptotic effect of Aralia echinocaulis extract on fibroblast-like synoviocytes in rats wi 2019 Apr Aralia echinocaulis is used for the treatment of rheumatoid arthritis by Tujia Minority in China. A previous study demonstrated that A. echinocaulis had a significant anti-arthritic effect on adjuvant arthritis (AA) rats in vivo. However, it remains unclear whether A. echinocaulis can induce the apoptosis of fibroblast-like synoviocytes (FLS) from AA rats and the underlying mechanism is unknown. In this paper, CCK-8 assay, Hoechst staining and flow cytometry were used to evaluate the apoptotic effect of an A. echinocaulis ethanol extract (AEE) on AA FLS. Western blotting analysis was performed to measure the protein expression levels of Bcl-2, Bax, cleaved caspase-3, Akt, p-Akt, and Hif-1α. The results revealed that AEE could inhibit FLS proliferation in a dose and time-dependent manner. After treatment with AEE, AA FLS displayed the classical apoptotic morphology, and the apoptosis rates were significantly increased. Furthermore, we found that AEE increased the protein levels of Bax, cleaved caspase 3, and decreased the protein levels of Bcl-2, Hif-1α and p-Akt, without affecting total Akt levels. Collectively, these results suggested that the apoptosis inducing effect of AEE on AA FLS was related to the regulation of the expression of apoptosis-related proteins and the inhibition of the Akt/Hif-1α signaling pathway.
31522189 Sugar and the Mosaic of Autoimmunity. 2019 Sep 15 BACKGROUND Recent discoveries in the field of immunometabolism, and on the role of the serine-threonine kinase mTOR as a sensor of nutrients, integrator of cellular signaling pathways, and regulator of metabolism, have widened our understanding of the connection between nutrition, health, and diseases. Epidemiological studies have shown that higher sugar-sweetened beverage consumption is associated with increased risk of developing chronic diseases, including cardiovascular disease, type 2 diabetes mellitus, obesity, non-alcoholic fatty liver disease, gout, and rheumatoid arthritis and to worse symptoms in some patients with rheumatoid arthritis. Anabolic metabolism has been demonstrated to favor the differentiation of proinflammatory T lymphocytes while katabolic metabolism to favor regulatory T lymphocyte differentiation. CASE REPORT In a 66-year old male, the onset of gonarthritis and enthesitis and worsening of these symptoms 3 months later were associated with excessive intake of desserts. Two weeks after starting strict avoidance of sugar containing nutrients and beverages symptoms disappeared. During the next 6 months, on 3 occasions, the exceptional consumption of a dessert was followed by a mild and transient recurrence of the symptoms. CONCLUSIONS The repeatedly observed recurrence of enthesitis/arthritis symptoms following sugar intake and its disappearance following avoidance of sugar, represents an extreme example of a link between metabolism and local inflammation in the reported individual. The rapid absorption of the monosaccharides glucose and fructose from the intestine, where they derive from hydrolysis of the disaccharide sucrose (sugar) might lead to overactivation of mTOR if not counterbalanced by other mTOR interfering mechanisms.
31258900 Expression profiling of genes in rheumatoid fibroblast-like synoviocytes regulated by tumo 2019 Jul Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation in synovial tissues. Hyperplasia of synovial tissue leads to the formation of pannus, which invades joint cartilage and bone resulting in joint destruction. Tumor necrosis factor-like ligand 1A (TL1A), a member of the tumor necrosis factor superfamily (TNFSF15), contributes to the pathogenesis of autoimmune diseases, including RA. In the present study, a cDNA microarray was used to search for genes whose expression in rheumatoid fibroblast-like synoviocytes (RA-FLS) were regulated by TL1A. Four individual lines of primary cultured RA-FLS were incubated either with recombinant human TL1A protein or phosphate-buffered saline, as an unstimulated control, for 12 h. Gene expression was then detected through the microarray assay. The results revealed the expression profiles of genes in RA-FLS regulated by TL1A. The present study also demonstrated the functions of those genes whose expression in RA-FLS was regulated by TL1A. Among the genes in this profile, the present study focused on the following genes: Spectrin repeat-containing nuclear envelope 1, Fc receptor-like 2, PYD (pyrin domain)-containing 1, cell division cycle 45 homolog, signal transducer and activator of transcription 5B, and interferon regulatory factor 4. These genes may affect the pathogenesis of RA, including proliferation, regulation of B cells and T cells, inflammation, and cytokine processing. The present study revealed for the first time, to the best of our knowledge, the expression profile of genes in RA-FLS regulated by TL1A. The data indicate that TL1A may regulate the gene expression of various key molecules in RA-FLS, thus affecting the pathogenesis of RA. Further investigations of the genes detected in the current profiles may provide a deeper understanding of the pathogenesis and a novel target for the treatment of RA.
31673424 Correction: ACPA and RF as predictors of sustained clinical remission in patients with rhe 2019 [This corrects the article DOI: 10.1136/rmdopen-2018-000738.].
31354962 Correction: Low rates of radiographic progression of structural joint damage over 2 years 2019 [This corrects the article DOI: 10.1136/rmdopen-2019-000898.].
31908843 Correction: Abatacept in combination with methotrexate in Japanese biologic-naive patients 2019 [This corrects the article DOI: 10.1136/rmdopen-2018-000813.].
31500394 Physician Adherence to Treat-to-Target and Practice Guidelines in Rheumatoid Arthritis. 2019 Sep 8 Principles of treat-to-target (T2T) have been widely adopted in both multinational and regional guidelines for rheumatoid arthritis (RA). Several questionnaire studies among physicians and real-world data have suggested that an evidence-practice gap exists in RA management. Investigating physician adherence to T2T, which requires a process measure, is difficult. Different practice patterns among physicians are observed, while adherence to protocolized treatment declines over time. Rheumatologist awareness, agreement, and claims of adherence to T2T guidelines are not always consistent with medical records. Comorbidities, a difficult disease course, communication barriers, and individual preferences may hinder an intensive, proactive treatment stance. Interpreting deviations from protocolized treatment/T2T guidelines requires sufficient clinical context, though higher adherence seems to improve clinical outcomes. Nonmedical constraints in routine care may consist of barriers in healthcare structure and socioeconomic factors. Therefore, strategies to improve the institution of T2T should be tailored to local healthcare. Educational interventions to improve T2T adherence among physicians may show a moderate, although beneficial effect. Meanwhile, a proportion of patients with inadequately controlled RA exists, while management decisions may not be in accordance with T2T. Physicians tend to be aware of current guidelines, but their institution in routine practice seems challenging, which warrants attention and further study.
31777783 Persistence of Tofacitinib in the Treatment of Rheumatoid Arthritis in Open-Label, Long-Te 2019 Apr OBJECTIVE: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This post hoc analysis evaluated tofacitinib persistence in patients with RA in long-term extension (LTE) studies up to 9.5 years. METHODS: Data were pooled from two LTE studies: ORAL Sequel (NCT00413699) and Study A3921041 (NCT00661661). Patients received tofacitinib 5 or 10 mg twice daily (BID), as monotherapy or with background conventional synthetic disease-modifying antirheumatic drugs. Kaplan-Meier estimates for tofacitinib drug survival and reasons for discontinuation were evaluated. Baseline factors were analyzed as predictors of persistence. RESULTS: In 4967 tofacitinib-treated patients entering LTE studies, mean (maximum) treatment duration was 3.5 (9.4) years. Median drug survival (95% confidence interval) was 4.9 (4.7, 5.1) years. Estimated 2- and 5-year drug survival rates were 75.5% and 49.4%, respectively. Median drug survival was similar between the tofacitinib 5 and 10 mg BID groups, and slightly higher for patients receiving tofacitinib monotherapy versus combination therapy. Overall, 50.7% of patients discontinued tofacitinib; of these, 47.2% were due to adverse events and 7.1% for lack/loss of efficacy. An increased risk of discontinuation was associated with baseline diabetes, hypertension, negative anticyclic citrullinated peptide (anti-CCP), negative rheumatoid factor (RF), and inadequate response to tumor necrosis factor inhibitors (TNFi-IR). CONCLUSION: Median drug survival of tofacitinib-treated patients participating in LTE studies was approximately 5 years and was similar for tofacitinib dosed at 5 and 10 mg BID. Reduced drug survival was associated with negative anti-CCP/RF status, TNFi-IR, and certain comorbidities. These data support tofacitinib use for long-term management of RA.
31476301 Regenerative effects of glycyrrhizin and/or platelet rich plasma on type-II collagen induc 2019 Oct 30 Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease manifested by joint destruction and deformity, hence decreasing patient's life quality. The aim of the present work is to explore the mechanistic effects of glycyrrhizin (GL)and/or platelet rich plasma (PRP) treatment on collagen induced arthritis. 75 female Wistar rats were allocated into five equal groups. Group I: control group. Group II: arthritis group (A group); arthritis was induced by type-II collagen Group III: Glycyrrhizin treated group(A + GL group), Group IV: platelet rich plasma treated group(A + PRP group)and Group V: combined treatment group(A + GL + PRP group). Hind paw joint tissue levels of high-mobility group box 1 protein (HMGB-1), beclin-1 and nuclear factor (erythroid-2)-related factor 2 (Nrf2) DNA binding activity were detected by ELISA. Activities of myeloperoxidase (MPO) and catalase enzymes were determined spectrophotometrically. mRNA expression levels of microtubule associated protein light chain 3 (LC3) was detected by quantitative real time PCR. After 8 weeks treatment, there was improvement of inflammation and autophagy biomarkers by the significant reduction of HMGB-1 and beclin-1 levels, down regulation ofLC3mRNA expression. On the other hand, we monitored restoration of the anti-oxidant status through the inhibited MPO activity besides induction of both catalase and Nrf2-DNA binding activities. It could be concluded that, the mutual use of both PRP and GL had a greater effect than each alone against arthritis which is considered a novel finding that can highlight the regenerative and ameliorative effects of this combined treatmentthus launching promising avenues for RA treatment.
31832792 Proteomic profile of saliva collected directly from ducts: a systematic review. 2020 Feb OBJECTIVE: To present a systematic review that provides updated information about proteins found in salivary fluid extracted strictly from ducts. METHODS: The systematic review probing strategy was based on electronic databases word search (PubMed, EMBASE, LILACS, Web of Science, and Scopus). Risk of bias was assessed based on Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. RESULTS: After 2 rounds of scrutiny, 12 articles were included, totaling 231 individuals (125 were healthy, 41 were elder individuals with radicular caries, 56 had primary Sjögren's syndrome, and 9 were patients who had received radiotherapy for head and neck cancer). The selected studies had no similarities among proteins found, demonstrating the need of standard reference in experimental methodology to obtain a thorough coverage of proteins. CONCLUSION: Further studies are required to better determine the relative amount of proteins described in this study. It is essential to increase the number of samples, to perform similar collection techniques, to include other analyses methods such as mass spectrometry, and to perform the validation of some proteins using immunoassay techniques such as Elisa and Western blot. CLINICAL RELEVANCE: Proteomic profile of saliva collected from ducts is essential to better understand the disease process, enabling the identification of biomarkers for specific clinical situations.
31634487 Primary Sjögren's syndrome and the eye. 2020 Mar Primary Sjögren syndrome is an autoimmune disease that mainly affects exocrine glands such as the salivary and lacrimal glands. In addition, systemic involvement is common. Primary Sjögren syndrome is of particular interest to ophthalmologists as it constitutes an important differential diagnosis in conditions with dry eye disease. In addition, ocular tests for more precisely diagnosing and monitoring primary Sjögren syndrome have become increasingly important, and new therapeutics for local and systemic treatment evolve as a result of increased understanding of immunological mechanisms and molecular pathways in the pathogenesis of primary Sjögren syndrome. We provide an update of interest to ophthalmologists regarding pathogenesis, diagnosis, investigative procedures, and treatment options.
30873941 Differential expression of miR-17-92 cluster among varying histological stages of minor sa 2019 May OBJECTIVES: To investigate the differential expression of miR-17-92 cluster, which encodes 6 microRNAs (miR-NAs) including miR-17, miR-18a, miR-19a, miR-19b, miR-20a and miR-92a, among varying histological stages of labial minor salivary gland (MSG) tis- sues in patients with primary Sjögren's syndrome (pSS). METHODS: Fifty-seven pSS patients and 13 healthy volunteers were enrolled in this study. The pSS patients were allocated to 3 subgroups of advanced clinical stages according to the histological findings of the MSG biopsies. Salivary flow rate, Schirmer test and some laboratory indexes were also tested. The expression levels of the 6 miRNAs in MSG were evaluated using quantitative real-time polymerase chain reaction with TaqMan miRNA assay. RESULTS: The differences between the healthy individuals and the 3 pSS subgroups were statistically significant for positive findings of salivary flow rate, Schirmer test and laboratory indexes. In the labial MSG tissues, we observed that the expression level of miR-18a was significantly up-regulated in patients of the 3 pSS subgroups compared to healthy individuals, while the expression level of miR-92a was significantly down-regulated. We also observed that there was no notable difference in the expression levels of miR-17, miR-19a, miR-19b, and miR-20a. Furthermore, we distinguished that miR-18a was progressively up-regulated along the advanced histological stages of the 3 pSS subgroups, while the miR-92a was progressively down-regulated. CONCLUDIONS: This is the first study on the expression of the miR-17-92 cluster in MSG of pSS patients. The association of increased expression levels of miR-18a and reduced expression levels of miR-92a with advanced clinical stages of pSS could significantly reduce the substantial subjectivity of scoring inflammatory infiltrates and may aid in the diagnosis of pSS.
31214753 SERS-based liquid biopsy of saliva and serum from patients with Sjögren's syndrome. 2019 Sep In this preliminary study, we employed surface-enhanced Raman scattering (SERS) of saliva and serum samples for diagnosing Sjogren's syndrome (SjS), a systemic autoimmune disease characterized by dryness of the mouth and eyes. The saliva and serum samples from n = 29 patients with SjS and n = 21 controls were deproteinized with methanol and then the SERS spectra were acquired using silver nanoparticles synthesized by reduction with hydroxylamine hydrochloride. In the case of both saliva and serum, the SERS spectra were dominated by similar bands attributed to purine metabolites such as uric acid, xanthine, and hypoxanthine. Principal component analysis-linear discriminant analysis (PCA-LDA) models built from SERS spectra of saliva and serum yielded an overall classification accuracy of 94% and 98%, respectively. These results suggest that the SERS analysis of saliva and serum is able to capture the complex biochemical perturbations that accompany the onset of SjS, a strategy which could be translated in the future into a novel point-of-care diagnosis method. Graphical abstract.
31376268 Type I interferon signature in Sjögren's syndrome: pathophysiological and clinical implic 2019 May Type I interferons (IFN) have long been recognised as mediators of innate immune defense mechanisms against viral threats. Robust evidence over the last 15 years revealed their significant role in the pathogenesis of systemic autoimmune diseases, including systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). Despite the progress, methods of detection, initial triggers, biological functions and clinical associations in the setting of autoimmunity remain to be fully clarified. As therapeutic options for SS are currently limited, neutralising specific targets of the type I IFN pathway seems a promising option. In this review we summarise the current evidence regarding the role of type I IFN in SS.
31417323 Physical activity and sedentary behavior in women with rheumatoid arthritis: a comparison 2019 Objective: In rheumatoid arthritis (RA) patients, low levels of physical activity (PA) and high levels of sedentary behavior (SB) may play a role in enhancing cardiovascular risk. We do not know how long-term control of disease activity impacts upon daily PA levels and if treated patients attain PA levels seen in healthy controls. We therefore compared habitual levels of PA and SB between female RA patients with low disease activity achieved by anti-tumor necrosis factor (TNF) therapy, those with active arthritis (aRA) and non-RA controls. Methods: We carried out a cross-sectional comparison of 40 RA patients on anti-TNF therapy for >2 years with DAS28<3.2 (tRA), 32 patients on conventional disease modifying anti-rheumatic drugs with DAS28>3.2 (aRA) and 34 healthy controls (C) with the groups matched for age and body mass index. PA was assessed using the ActiGraph accelerometer to determine step count and time spent in moderate-to-vigorous physical activity (MVPA), light activity and sedentary time. Results: Daily step count was 72% higher in tRA and 40% higher in C in comparison to aRA (p<0.01). Sedentary time (as a proportion of wear time) was 10% less in tRA than aRA (p=0.03), while light activity time was 18% higher (p=0.014). Both RA groups had 40% lower MVPA time than C (p=0.001). Only half of either RA group fulfilled current WHO guidelines for PA compared with 82% of controls. Conclusion: RA patients who had long-term disease suppression were more physically active with less SB compared to RA patients with active disease. They had similar light PA and SB to controls although lower MVPA. Behavioral change interventions are likely to be needed in order to restore moderate exercise, further reduce SB and to meet guidelines for daily PA.
30936951 Risk factors associated with periprosthetic joint infection after total elbow arthroplasty 2019 Apr BACKGROUND: For patients undergoing total elbow arthroplasty (TEA), the present study aimed to investigate: (i) what risk factors are associated with periprosthetic elbow infection; (ii) what is the incidence of infection after TEA; and (iii) what is the acuity with which these infections present? METHODS: The Statewide Planning and Research Cooperative System database was used to identify all patients who underwent TEA between 2003 and 2012 in New York State. Admissions for prosthetic joint infection (PJI) were identified using ICD-9 (International Classification of Diseases, Ninth Revision, Clinical Modification) diagnosis code 996.66. Multivariate analysis was used to determine risk factors that were independently prognostic for PJI. RESULTS: Significant risk factors for PJI included hypothyroidism [odds ratio (OR) = 2.04; p = 0.045], tobacco use disorder (OR = 3.39; p = 0.003) and rheumatoid arthritis (OR = 3.31; p < 0.001). Among the 1452 patients in the study period who underwent TEA, 3.7% (n = 54) were admitted postoperatively for PJI. There were 30 (56%) early infections, 17 (31%) delayed infections and seven (13%) late infections. CONCLUSIONS: Pre-operative optimization of thyroid function, smoking cessation and management of rheumatoid disease may be considered in surgical candidates for TEA. The results of the present study add prognostic data to the literature that may be helpful with patient selection and risk profile analysis. LEVEL OF EVIDENCE: Level III: prognostic study.
31186080 T lymphocyte dependence of the immune response to immunosuppressive neoantigen-exposing Fc 2019 May We recently identified a rheumatoid factor associated with autoimmune disease resistance and remission, and have named it regulatory rheumatoid factor (regRF). Epitopes recognized by regRF can be induced in papain Fc fragments of IgG. Immunization of arthritic rats with homologous Fc fragments that expose neoepitopes recognized by regRF reduces the symptoms of collagen-induced arthritis. Therefore, regRF-producing lymphocytes are a promising therapeutic target in arthritis, and Fc fragments are a means of stimulating this target.
30660454 Scientific validation of anti-arthritic effect of Kashayams - A polyherbal formulation in 2021 Jan BACKGROUND: Toll-like receptor-4 (TLR-4) mediates activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) resulting in induction of proinflammatory genes such as that encoding tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) which played a significant role in cartilage destruction of rheumatoid arthritis (RA). Low risk and better efficacy made herbal drugs more reliable than nonsteroid anti-inflammatory drugs (NSAIDS) in RA treatment. Gugguluthiktam Kashayam (GuK), Punarnavadi Kashayam (PuK) and Balaguluchiadi Kashayam (BgK) are ayurvedic polyherbal formulations prescribed in classical ayurvedic texts Sahasrayogam and Ashtangahridayam as medicines for the treatment of RA. OBJECTIVE: The objective of the present study was to elucidate the molecular mechanism of anti-arthritic effect of these Kashayams on TLR-4 signal transduction pathway in collagen induced arthritic rats. MATERIAL AND METHODS: The wistar rats grouped into group I - Normal, group II- Collagen induced arthritis (CIA), group III- CIA + BgK, group IV- CIA + PuK, group V- CIA + GuK, group VI - CIA + Indomethacin (3 mg/kg b.wt.). Treatment with Kashayam (2 ml/kg b.wt) started after 14 days of primary immunization with type II collagen and continued for a period of 45 days. RESULTS: Arthritis index, C-reactive protein (CRP), rheumatoid factor (RF) and myeloperoxidase (MPO) in serum and protein level of TLR-4, myeloid differentiation factor 88 (MYD88), NF-κB, TNF-α, IL-1β, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 COX-2) and prostaglandin E-2 (PGE-2) in cartilage were significantly elevated in CIA rats. Further, treatment with Kashayams downregulated all these inflammatory mediators hitherto TLR-4-NF-kB signal transduction pathway except IL-10, an anti-inflammatory cytokine which showed a reverse effect. CONCLUSION: This molecular mechanism of the investigation confirmed the clinical efficacy of Kashayams in preventing the progression of RA and gave an intuition of the scientific validation of Kashayams, an Ayurvedic classical medicine.
31240499 Patterns of Prednisone Use in Patients with Rheumatoid Arthritis Initiating Treatment with 2019 Sep INTRODUCTION: Prednisone is frequently administered in combination with other therapies for the treatment of rheumatoid arthritis (RA); however, its chronic use is associated with an increased risk of comorbidities and mortality. The objective of this analysis was to evaluate changes in prednisone use among patients with RA treated with tocilizumab (TCZ) in routine US clinical practice. METHODS: TCZ-naïve patients in the Corrona RA registry who initiated TCZ were included. The primary outcome was the proportion of patients with changes in prednisone use over 12 months (primary analysis) and 6 months (secondary analysis). Changes in disease activity over 6 and 12 months (± 3 months) were assessed using the Clinical Disease Activity Index (CDAI). Outcomes were assessed in the overall population and separately for patients receiving TCZ monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs. RESULTS: Of patients receiving prednisone at baseline (mean [SD] dose: 7.7 [5.2] mg/day), 30.6% discontinued prednisone over 12 months; among patients receiving > 7.5 mg of prednisone at the time of TCZ initiation, 63.0% discontinued prednisone or decreased their dose by ≥ 5 mg over 12 months. In secondary analyses, 29.7% of patients receiving prednisone at baseline had discontinued prednisone over 6 months; among those receiving > 7.5 mg of prednisone at baseline, 51.3% discontinued or decreased their dose by ≥ 5 mg over 6 months. Changes in prednisone use and improvement from baseline in CDAI score over 6 and 12 months were comparable between patients who initiated TCZ monotherapy vs. TCZ combination therapy. CONCLUSIONS: In this real-world analysis, many patients initiating TCZ monotherapy or combination therapy were able to discontinue or decrease their prednisone dose over 12 months. Similar changes in prednisone dose were observed over 6 months. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01402661. FUNDING: Corrona, LLC and Genentech, Inc. Plain language summary available for this article.
31622314 Recurrent aseptic meningitis: A rare clinical presentation of Sjogren's syndrome. 2019 Oct Sjogren's syndrome most commonly presents with dry eyes, dry mouth, joint pain and fatigue. However, recurrent aseptic meningitis, reported as the most uncommon initial symptom, was the presenting feature in our case. We present the case of a 19-year-old female with recurrent episodes of aseptic meningitis. She presented with fever, headache, vomiting and photophobia. Neurological examination showed neck stiffness. Fundoscopy was normal. On two previous occasions her cerebrospinal fluid analysis was consistent with meningitis; however, it was normal at this presentation. Review of system revealed history of fatigue and sicca symptoms since early childhood. Autoimmune workup showed antinuclear antibodies with a titer of 1:400 and positive anti SSA (Ro) antibodies that led to the diagnosis of Sjogren's syndrome. She responded well to intravenous steroids, followed by oral prednisolone and hydroxychloroquine. To conclude, diagnosis of Sjogren's syndrome may also be considered in a patient presenting with recurrent aseptic meningitis.