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ID PMID Title PublicationDate abstract
31488308 AA amyloidosis secondary to adult onset Still's disease: About 19 cases. 2020 Feb OBJECTIVE: Adult onset Still's disease (AOSD) is an inflammatory disorder characterized by high spiking fever, evanescent rash, polyarthritis, and many other systemic manifestations. Recurrent or persistent disease can lead to AA amyloidosis (AAA). Our objectives were to present 3 French cases and perform a systematic review of the literature, in order to determine the prevalence, characteristics, predisposing factors, and therapeutic response of AOSD-related AAA. METHODS: A systematic literature review was performed by searching MEDLINE from 1971 to 2018. Two independent investigators selected reports of AAA complicating AOSD. New French cases were identified with the help of the Reference Center for rare Auto-Inflammatory Diseases and Amyloidosis (CEREMAIA). Patients with juvenile idiopathic arthritis were excluded. RESULTS: The prevalence of AAA in AOSD was 0.88% (95%CI [0.49-1.28]) based on 45 articles. In addition to 3 new cases from the CEREMAIA, 16 patients were assessed for clinical presentation, risk factors, and therapeutic response of AOSD-related AAA. Mean age at AOSD onset was 29.6 ± 12.6 years, with a mean delay before AAA diagnosis of 16.75±5.8 years. Renal involvement was the most common manifestation of AAA. The majority of patients presented active AOSD at AAA diagnosis. Various treatments of AOSD-related AAA were attempted including corticosteroids and biotherapies. CONCLUSION: AAA is a rare and severe complication that may occur during the course of uncontrolled active AOSD. It could be prevented by early diagnosis and better control of AOSD, with more frequent use of biotherapies.
31273637 Clinicopathologic features of rheumatoid nodules: a retrospective analysis. 2019 Nov OBJECTIVES: The clinical and histopathologic features of patients that have been diagnosed with rheumatoid nodules were investigated. METHODS: This study included patients with rheumatoid nodules, confirmed by histologic assessment, between 2005 and 2018 at the Hanyang University Hospital. Each patient had a total score of 6 or more according to the American College of Rheumatology criteria. RESULTS: A total of 57 cases were included in this study. The median age of the patients at the time of diagnosis was 57 years (range, 39-70 years). The average duration between the onset of treatment and occurrence of rheumatoid nodule was 11.6 years. Bone erosion was observed in 44 patients (77.2%). Among 57 patients, 56 (98.2%) were treated with disease-modifying anti-rheumatic drugs; most of the patients (87.7%) showed high-positive rheumatoid factor or high-positive anti-citrullinated protein antibodies. The foot, hand, and wrist, in order of decreasing frequencies, were the anatomical sites with the highest occurrence of rheumatoid nodules, whereas, the soft tissue adjacent to the joint, subcutis, dermis, lung parenchyma, and submucosal layer of the supraglottic area, also in an order of highest frequency, were the histological sites with the highest occurrence. Microscopically, central necrobiosis was present in all cases. Stromal fibrosis (96.5%), palisading of histiocytes (82.5%), perivascular lymphocytic infiltration (68.4%), and cleft or cystic degeneration (63.2%) were also observed. CONCLUSIONS: A clinicopathological review of cases diagnosed with rheumatoid nodules histologically was performed to confirm characteristics that can help clinicians understand the pathophysiology of the condition and make accurate diagnoses of rheumatoid nodules. Key Points • We reviewed the clinical, imaging, and histologic features of rheumatoid nodule. • The average duration between the onset of treatment and occurrence of rheumatoid nodule was 11.6 years. • Among 57 rheumatoid nodule patients, 98.2% were treated with disease-modifying anti-rheumatic drugs.
31849678 Network Pharmacology-Based Prediction of Active Ingredients and Mechanisms of Lamiophlomis 2019 Background: Lamiophlomis rotata (LR) showed favorable clinical effect and safety on rheumatoid arthritis (RA), but its active ingredients and mechanisms against RA remain unknown. The aim of this work was to explore the active ingredients and mechanisms of LR against RA by network pharmacology. Methods: Compounds from LR were identified using literature retrieval and screened by absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluation. Genes related to the selected compounds or RA were identified using public databases, and the overlapping genes between compounds and RA target genes were identified using Venn diagram. Then, the interactions network between compounds and overlapping genes was constructed, visualized, and analyzed by Cytoscape software. Finally, pathway enrichment analysis of overlapping genes was carried out on Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Results: A total of 148 compounds in LR were identified, and ADMET screen results indicated that 67 compounds exhibited good potential as active ingredients. A total of 90 compounds-related genes and 1,871 RA-related genes were identified using public databases, and 48 overlapping genes between them were identified. Cytoscape results suggested that the active ingredients and target genes of LR against RA consisted of 23 compounds and 48 genes, and luteolin and AKT1 were the uppermost active ingredient and hub gene, respectively. DAVID results exhibited that the mechanisms of LR against RA were related to 34 signaling pathways, and the key mechanism of LR against RA might be to induce apoptosis of synovial cells by inactivating PI3K-Akt signaling pathway. Conclusion: The active ingredients and mechanisms of LR against RA were firstly investigated using network pharmacology. This work provides scientific evidence to support the clinical effect of LR on RA, and a research basis for further expounding the active ingredients and mechanisms of LR against RA.
31695863 Stromal cell-derived factor-1 as a potential therapeutic target for osteoarthritis and rhe 2019 With age, joints become subject to chronic inflammatory processes that lead to degeneration of articular cartilage. Although multifactorial, cytokines have been shown to play a role in the pathogenesis of these chronic disease states. Stromal cell-derived factor 1 (SDF-1) is a chemokine that has been shown to be active in homeostatic mechanisms and developmental processes throughout the body, such as endochondral bone formation. SDF-1 plays a role in the transition from cartilage to bone. Although it has been shown to be a factor in normal development, it has also been shown to involve in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA). In RA, SDF-1 has been shown to stimulate the recruitment of proinflammatory cells, as well as osteoclasts to the synovium, aiding in the facilitation of synovial degradation. Similarly, in OA, SDF-1 has been shown to regulate key proteins involved in the degradation of the cartilage of the joint. Because of its role in degenerative joint disease, SDF-1 has been investigated as a potential therapeutic target. Animal studies have been employing SDF-1 inhibitors, such as AMD3100 and T140, to study their effects on attenuating degenerative joint disease. These studies have shown promising results in slowing the progression of cartilage degradation and could potentially be used as therapeutic target for humans OA and RA.
31592115 The Increased RNase Activity of IRE1α in PBMCs from Patients with Rheumatoid Arthritis. 2019 Aug Purpose: Despite recent advances in the diagnosis and treatment of rheumatoid arthritis (RA), this inflammatory disease remains a challenge to patients and physicians. Recent evidence highlights the contribution of endoplasmic reticulum (ER) stress in the pathogenesis and treatment of RA. Herein, we study the expression of the ER stress sensor inositol-requiring enzyme 1α (IRE1α), as well as XBP1 splicing and the regulated IRE1-dependent decay (RIDD), in peripheral blood mononuclear cells (PBMCs) from patients with RA compared with healthy controls. Methods: The PBMCs from blood samples of RA patients and healthy volunteers were isolated by a density gradient centrifugation method using Ficoll. The gene expression levels of GRP78/ Bip, IRE1, XBP1s, micro-RNAs (miRNAs) were evaluated by real-time PCR. Results: The expression of GRP78, IRE1, and XBP1s were increased in PBMCs of RA patients compared with healthy controls. We further show that the RIDD targets (miRNA-17, -34a, -96, and -125b) were downregulated in RA samples. Conclusion: This study can expand our knowledge on the importance of RNase activity of IRE1α in RA and may offer new potentials for developing novel diagnostic and/or therapeutic biomarkers.
31530986 Associations of TRAF1/C5 rs10818488 and rs3761847 polymorphisms with genetic susceptibilit 2019 The results on associations of tumor necrosis factor (TNF)-receptor associated factor 1/complement component 5 (TRAF1/C5) rs10818488 and rs3761847 polymorphisms with rheumatoid arthritis (RA) are controversial, thus this study was performed to examine whether the aforementioned polymorphisms were associated with RA in a Chinese population. Furthermore, an updated meta-analysis was conducted. The polymorphisms were genotyped in 328 Chinese RA patients and 449 healthy controls. Studies examining the association of TRAF1/C5 rs10818488 and/or rs3761847 polymorphism with RA were exhaustively searched. No significant difference in either genotype or allele distribution between RA patients and controls was found. The updated meta-analysis was conducted based on 19 articles including the present study. A significant association of RA with TRAF1/C5 rs10818488 polymorphism G allele in Europeans (OR = 0.843, 95% CI = 0.730-0.975, p = 0.021) and in Asians (OR = 1.070, 95% CI = 1.009-1.136, p = 0.024) was found. Additionally, a significant association of RA with TRAF1/C5 rs10818488 polymorphism G allele under the recessive model in Asians (OR = 1.129, 95% CI = 1.023-1.246, p = 0.016) and in Africans (OR = 0.657, 95% CI = 0.507-0.851, p = 0.001) was found. Only a borderline significant association of RA with TRAF1/C5 rs3761847 polymorphism A allele was found in Europeans. Non-significant associations of RA with TRAF1/C5 rs10818488 and rs3761847 polymorphisms were found in our study. The updated meta-analysis results demonstrate that TRAF1/C5 rs10818488 polymorphism is associated with RA in Europeans, Asians and Africans, and TRAF1/C5 rs3761847 polymorphism is associated with RA in Europeans with borderline significant evidence.
31426398 Rheumatoid Arthritis Treatment. A Back to the Drawing Board Project or High Expectations f 2019 Aug 16 Despite the significant progress in Rheumatoid Arthritis (RA) therapeutics, there are several reports in the literature claiming that the size of unmet needs in RA is large. In the era before biologics, there was indeed a significant number of patients who did not achieve low disease activity (LDA) or disease remission due to limited therapeutic choices in the doctors' armamentarium. Treatment wise, great progress has been achieved over the last decades with the discovery and introduction in therapeutics of new molecules, such as the biological (b) disease-modifying anti-rheumatic drugs (DMARDs), and the targeted synthetic (ts) DMARDs. Today, with such a plethora of conventional synthetic (cs) DMARDs, tsDMARDs, and bDMARDs, why are we unable to successfully treat RA patients? What is wrong? However, a new drug for RA does not mean it is necessary to switch to a new treatment. It is very easy to change and switch therapies when the patient complains about pain and stiffness. In this setting, it is obligatory to rule out other comorbidities and disorders that may be the cause of the pain first. Thus, clinicians must have a deep knowledge of the drug therapy and be able to adjust the treatment when needed. A minute clinical examination must be carried out on every visit with close monitoring of the patient. A treat-to-target (T2T) approach and the application of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) recommendations and strategies should minimize the unmet needs.
31027874 [Sjögren's syndrome update: Clinical and therapeutic aspects]. 2019 Jul Sjögren's syndrome (SS) is a systemic orphan disease. It is characterized by the involvement of epithelial tissues leading to the term of autoimmune epithelitis. New classification criteria have been developed in 2016. New scores have also been developed: a patient-reported outcome called ESSPRI and a score assessing systemic activity of the disease called ESSDAI. These new tools are very helpful to better stratify patients and to customize the management of this very heterogeneous disease. Among the autoimmune diseases, SS is associated with the highest risk of lymphoma. Five to ten percent of the patients will have a B cell lymphoma mostly a low-grade lymphoma developing from mucosa-associated lymphoid tissue (MALT). Major advances have been made in this field: pathogeny is better understood, new predictors are available and progresses have been made in the management of this severe complication. Research in the field of SS is very dynamic as illustrated by the high number of therapeutic trials. There is hope that these innovations, reviewed in the present article, will have potential significant repercussions for the patients in the next few years.
30891620 ESSDAI activity index of the SJÖGRENSER cohort: analysis and comparison with other Europe 2019 Jun The objective of the study was to assess the ESSDAI index characteristics in the SJÖGRENSER cohort (Spanish Rheumatology Association's registry of patients with Primary Sjögren Syndrome [PSS]). SJÖGRENSER is a prospective multicentric study on a cohort of Spanish patients with PSS who meet the 2002 American-European consensus from rheumatology units. 298 variables were studied in patients for the inclusion of the study from an anonymous list from each department. The ESSDAI (EULAR Sjögren's syndrome disease activity index) includes 12 domains and measures systematic activity in PSS patients. Each domain is divided into 3-4 levels, (0: no activity; 1: low activity; 2: moderate activity; 3: high activity) and is attributed a weight. Each domain score is obtained by multiplying the activity level by the weight assigned. According to ESSDAI: low activity < 5; moderate activity 5-13, and high activity ≥ 14. ESSDAI was compared between several European PSS cohorts (EULAR, ASSES, GEAS, GRISS, Ducth). 437 patients were included from 33 Spanish rheumatology units. 95.2% were women with a median age of 58.63 years [p25-p75: 50.02-67.98 years] and average PSS evolution of 10.4 years (6-16 years). ESSDAI median on entering the study was 2 (0-4). 31% of patients had ESSDAI 0; low activity 49%, moderate activity 15%, and high activity 5%. Those with greater activity were the joint, haematological and biological domains, whereas the lung was the most affected organ with pleural and parenchymatous involvement. Unlike other European cohorts, the initial SJÖGRENSER cohort was characterised by low-zero systemic activity in 80% of patients, which differentiates it from other cohorts and provides a prospective study opportunity.
30932443 Incidental papillary thyroid cancer diagnosis in patient with adult-onset Still's disease- 2019 Apr 1 Adult onset Still's disease (AOSD) is a systemic inflammatory disease characterized primarily by a triad consisting of daily fever, arthritis and maculopapular exanthema. The pathogenesis and etiology of AOSD are unknown and the diagnosis, which can be very challenging, is often made by exclusion. Here, we report a case of a 61-year-old woman with a history of mild psoriatic arthritis, fever, arthritis and maculopapular exanthema. Her initial laboratory tests showed neutrophilic leukocytosis, hypertransaminasemia, and markedly elevated levels of the erythrocyte sedimentation rate and C-reactive protein. With a presumptive diagnosis of AOSD, based on Yamaguchi criteria, the patient started an extensive diagnostic work-up to exclude other potential differential diagnoses. With fluorodeoxyglucose (FDG) positron-emission tomography, a thyroid nodule with moderate FDG uptakes was detected. The fine needle aspiration biopsy led to diagnosis of papillary thyroid cancer. The history of psoriatic arthritis, the patient's age, and atypical features of the skin rash described as not concomitant with fever flares, suggested a diagnosis of paraneoplastic AOSD-like manifestations.
30710221 Proposal for a simple algorithm to differentiate adult-onset Still's disease with other fe 2019 Jun OBJECTIVE: To identify several clinical and/or laboratory parameters which can differentiate adult-onset Still's disease (AOSD) from other causes of fever of unknown origin (FUO) and create a clinician-friendly algorithm for this purpose. METHODS: FUO patients hospitalized between March 2015 and September 2017 were recruited prospectively. AOSD patients diagnosed between 2001 and 2017 in our department were analyzed. Clinical and laboratory parameters were recorded for all patients. A multivariate analysis was performed to identify possible parameters related to the discrimination of AOSD from FUO. RESULTS: We recruited 69 AOSD patients (51 females, 74%) and 87 patients (43 females, 49.4%) evaluated for FUO. Median ages were 45 (30-57) and 45 (30-62), respectively. Arthralgia, rash, sore throat, neutrophilia, serum ferritin level higher than 5 times of the upper limit, and elevated lactate dehydrogenase levels were associated with the likelihood of diagnosing AOSD; on the other hand, the number of daily fever peaks equal or greater than 3 was associated with the unlikelihood of diagnosing AOSD. After the clinical feasibility assessment of possible parameters derived from the multivariate analysis, in the setting of fever, two clinical (arthralgia, sore throat) and two laboratory (ferritin level, neutrophilia) parameters were selected to develop an algorithm for discrimination of AOSD and FUO. CONCLUSION: Presence of arthralgia, hyperferritinemia, sore throat, and neutrophilia suggests AOSD in patients presenting as FUO. This study proposes a clinician-friendly algorithm for the first time in current literature to discriminate AOSD from other causes of FUO.
30444203 In vivo, Extract from Withania somnifera Root Ameliorates Arthritis via Regulation of Key 2019 BACKGROUND: Rheumatoid Arthritis (RA) is a devastating disease characterized by continual addition of leukocytes and T cells within the articular cavity causing inflammation and cartilage destruction. Withania somnifera is one of the most precious medicinal herbs, reported to have antioxidant, anti-inflammatory, and immunomodulatory properties. OBJECTIVE: The purpose of this study was to evaluate anti-inflammatory activity of aqueous extract of Withania somnifera roots (WSAq) in Collagen Induced Arthritic (CIA) rats. METHODS: To achieve this, we assessed the level of inflammatory cytokines such as Tumor Necrosis Factor (TNF)-α, IL-1β, IL-6 and IL-10 in CIA rats. Further, transcription factor, oxidative stress parameters and CD+8 expressions were also analyzed in CIA rats. RESULTS: Arthritic rats showed a greater increase in the levels of pro inflammatory cytokines such as TNF-α, IL-1β, IL-6, transcription factor NF-κB and a decrease in IL-10 concentration than controls rats. Oral administration of WSAq at a dose of 300mg/kg.wt. (WSAq300) appreciably attenuated the production of these pro inflammatory cytokines. This anti-inflammatory activity of WSAq300 might be partly mediated through an increase in the secretion of IL-10 and inhibition of NF-κB activity. Further, arthritic rats also show increased oxidative stress as compared to control rats. This increased oxidative stress in the arthritic rats appears to be the outcome of both an activated pro-oxidant and a poor antioxidant defense system. Treatment with WSAq300 strongly ameliorates all these ROS parameters significantly to near normal. Additional, metalloproteinase MMP-8 levels were also measured and found to be increased in CIA rats, which after treatment with WSAq300 came down to near normal. CONCLUSION: From the above results, it can be concluded that the use of WSAq300 may be a valuable supplement which can improve human arthritis.
31501931 In vivo imaging of early stages of rheumatoid arthritis by α5β1-integrin-targeted positr 2019 Sep 9 BACKGROUND: Rheumatoid arthritis (RA) is one of the most common rheumatic diseases. Joint inflammation and pathological growth of joint cartilage cause swollen and painful joints, which severely diminishes the patients' life quality. There is no causal treatment. Symptomatic therapies should start as early as possible to take maximal effect. Hence, diagnostic procedures capable of detecting affected joints before the onset of clinical symptoms are highly desirable. We explored the value of PET imaging of integrin subtypes αvβ3 and α5β1 for early detection of RA foci in collagen-induced arthritis (CIA) mouse models. RESULTS: Development of RA in CIA mice was monitored by paw scoring, and αvβ3- and α5β1-integrin expression was quantified by μPET using (68)Ga-Avebetrin and (68)Ga-Aquibeprin. For consecutive sections of selected decalcified joints (knee, ankle), arthritic degeneration and integrin expression were assessed by MOVAT staining and β3/α5 immunohistochemistry (IHC), respectively. β3- and α5-IHC revealed elevated levels of both αvβ3- and α5β1-integrin in arthritic joints. Unlike αvβ3, α5β1 is strongly expressed in the proliferating synovial lining layer, which suggests that its presence is directly related to RA development. For mice with advanced RA (6 weeks after CIA), PET signals for α5β1-integrin were substantially stronger (> 300% of baseline) than that of αvβ3-integrin (< 200%). A longitudinal PET follow-up revealed that the manifestation of clinical symptoms of RA is preceded by upregulation of α5β1- but not of αvβ3-integrin. CONCLUSION: α5β1-integrin PET could add a new functional imaging aspect to the portfolio of RA diagnostics because it appears to be a sensitive biomarker for early RA development. We suggest α5β1-integrin PET as a valuable tool to achieve a higher precision for early diagnosis of RA, including initial staging, monitoring of the disease course, and drug treatment, and for planning of radiosynoviorthesis (RSO).
31970018 Rheumatiod Arthritis: An Updated Overview of Latest Therapy and Drug Delivery. 2019 Dec Rheumatoid arthritis is a severe autoimmune disorder, related to joints. It is associated with serious cartilage destruction. This causes disability and reduces the excellence of life. Numerous treatments are existed to combat this disease, however, they are not very efficient and possess severe side effects, higher doses, and frequent administration. Therefore, newer therapies are developed to overcome all these limitations. These include different monoclonal antibodies, immunoglobulins, small molecules used for immunotherapy and transgenes for gene therapy. One of the main goals of these new generation therapeutics is to address the underlying distressing biological processes by specifically targeting the causative agents with fewer systemic side effects and greater patient console. It is very fortuitous that loads of progressive investigations are going on in this field and many of them have entered into the successful clinical trial. But till date, a limited molecule has got FDA clearance and entered the market for treating this devastating disease. This review highlights the overview of conventional therapy and advancements in newer therapeutics including immunotherapy and gene therapy for rheumatoid arthritis. Further, different novel techniques for the delivery of these therapeutics of active and passive targeting are also described.
31879201 Cost evolution of biological drugs in rheumatoid arthritis patients in a tertiary hospital 2021 Jun OBJECTIVE: To assess the evolution of cost per patient/year and the cost per patient/year/drug in patients with rheumatoid arthritis (RA) receiving biological treatments. To analyze and quantify the factors influencing this evolution, such as the optimization of the biological drugs, the use of biosimilars, and official discounts and discounts obtained after negotiated procedures. In addition, to assess specific clinical parameters of disease activity in these patients. METHODS: Retrospective, observational study conducted in a Spanish tertiary hospital. Adult patients diagnosed with RA under treatment from 2009 to 2017 were included. RESULTS: 320, 270 and 389 patients were included in 2009, 2013 and 2017, respectively. The patient/year cost decreased from 10,789€ in 2009, 7491€ in 2013 to 7116€ in 2017. In 2017, due to the established competition, discounts of 14% and 29.5% were achieved on etanercept and its biosimilar; 11.5%, 17.8%, 17.9%, 17.3% on adalimumab, certolizumab, golimumab and tocilizumab IV respectively, and 24.6% and 43.1% on infliximab and its biosimilar. The percentage of patients optimized in 2017 was 35.2%. The annual saving in 2017 was 1,288,535€ (830,000€ due to dose optimization and/or administration regimens, 249,666€ corresponding to 7.5% of the official discount and 208,868€ after negotiated procedures). CONCLUSION: The annual cost per patient in RA decreased considerably due to different factors, such as discounts on the purchase of drugs due to official discounts and negotiated procedures, together with the optimization of therapies, the latter being the factor that contributed most to this decrease.
31508906 Effects of autophagy on apoptosis of articular chondrocytes in adjuvant arthritis rats. 2019 Nov Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that eventually leads to joint deformities and loss of joint function. Previous studies have demonstrated a close relationship between autophagy and the development of RA. Although autophagy and apoptosis are two different forms of programmed death, the relationship between them in relation to RA remains unclear. In this study, we explored the effect of autophagy on apoptosis of articular chondrocytes in vivo and in vitro. Adjuvant arthritis (AA) and acid-induced primary articular chondrocyte apoptosis were used as in vivo and in vitro models, respectively. Articular chondrocyte autophagy and apoptosis were both observed dynamically in AA rat articular cartilage at different stages (15 days, 25 days and 35 days). Moreover, chondrocyte apoptosis and articular cartilage injury in AA rats were increased by the autophagy inhibitor 3-methyladenine (3-MA) and decreased by the autophagy activator rapamycin. In addition, pre-treatment with 3-MA increased acid-induced chondrocyte apoptosis, while pre-treatment with rapamycin reduced acid-induced chondrocyte apoptosis in vitro. These results suggest that autophagy might be a potential target for the treatment of RA.
30833991 IL-12/IL-23p40 identified as a downstream target of apremilast in ex vivo models of arthri 2019 BACKGROUND: Apremilast (Otezla(®)) is a phosphodiesterase 4 (PDE4) inhibitor approved for the treatment of psoriasis and psoriatic arthritis (PsA), but the reason why apremilast shows clinical effect is not fully understood. The objective of this study was to study the downstream effects of apremilast on cells of inflamed joints in immune-mediated inflammatory arthritis. METHODS: Synovial fluid was obtained from patients with active rheumatoid arthritis (RA), PsA or peripheral spondyloarthritis (SpA; n = 18). The in vitro models consisted of synovial fluid mononuclear cells (SFMCs) or fibroblast-like synovial cells (FLSs) cultured for 48 h, SFMCs cultured for 21 days, an osteoclast pit formation assay, and a mineralization assay. RESULTS: In SFMCs cultured for 48 h, apremilast decreased the production of interleukin (IL)-12/IL-23p40 (the shared subunit of IL-12 and IL-23), colony-stimulating factor 1, CD6, and CD40 and increased the production of C-X-C motif chemokine 5 dose-dependently. Apremilast had a very different response signature compared with the tumor necrosis factor alpha inhibitor adalimumab with a substantially greater inhibition of IL-12/IL-23p40. In SFMCs cultured for 21 days, apremilast increased the secretion of IL-10. In FLS cultures, apremilast decreased matrix metalloproteinase-3 production. Apremilast decreased osteoclastogenesis but did not affect mineralization by human osteoblasts. CONCLUSION: This study reveals the downstream effects of apremilast in ex vivo models of arthritis with a strong inhibition of IL-12/IL-23p40 by SFMCs. Our findings could explain some of the efficacy of apremilast seen in IL-12/IL-23-driven immune-mediated inflammatory diseases such as psoriasis and PsA.
30430560 The immunopathogenesis of fibrosis in systemic sclerosis. 2019 Mar Systemic sclerosis (SSc) is an idiopathic systemic autoimmune disease. It is characterized by a triad of hallmarks: immune dysfunction, fibrosis and vasculopathy. Immune dysfunction in SSc is characterized by the activation and recruitment of immune cells and the production of autoantibodies and cytokines. How immune abnormalities link the fibrosis and vasculopathy in SSc is poorly understood. A plethora of immune cell types are implicated in the immunopathogenesis of SSc, including T cells, B cells, dendritic cells, mast cells and macrophages. How these different cell types interact to contribute to SSc is complicated, and can involve cell-to-cell interactions and communication via cytokines, including transforming growth factor (TGF)-β, interleukin (IL)-6 and IL-4. We will attempt to review significant and recent research demonstrating the importance of immune cell regulation in the immunopathogenesis of SSc with a particular focus on fibrosis.
30488533 Gene polymorphisms and serum levels of TL1A in patients with rheumatoid arthritis. 2019 Jul Recent findings showed elevated expression of tumor necrosis factor (TNF)-like ligand 1A (TL1A) in rheumatoid arthritis (RA) patients and arthritis mice. However, whether TL1A gene polymorphisms may correlate with RA susceptibility needs to be discussed. This case-control study was performed on 350 RA patients and 556 healthy subjects to identify TL1A genetic variants (rs3810936, rs6478109, and rs7848647) and their possible association with TL1A levels, susceptibility to and severity of RA. Odds ratio and 95% confidence interval were calculated to represent the correlation between TL1A polymorphisms and RA. The TL1A serum levels were evaluated. Results showed that frequencies of TC, TT + TC genotypes of rs3810936, rs7848647 in RA patients were significantly lower in RA patients compared with controls. Patients with C allele showed more severe disease course (disease activity index: erythrocyte sedimentation rate, rheumatoid factor) than in carriers of T allele. However, the allele or genotype frequencies of rs6478109 were not associated with RA. In addition, TL1A genetic variants conferred higher TL1A levels in RA patients compared with controls. In conclusion, these findings indicated an association between TL1A rs3810936, rs7848647 variation and the susceptibility of RA in a sample of Chinese individuals, and TL1A may correlate with severity of RA.
31366877 Adverse Reaction of Dextran Sodium Sulfate-Induced Colitis in a Collagen-Induced Mouse Art 2019 The pathogenic relationship of ulcerative colitis and rheumatoid arthritis is not known. Therefore, we examined dextran sodium sulfate (DSS)-induced colitis separately and in combination with a mouse arthritis model that mimics rheumatoid arthritis and evaluated the deterioration-related factors of each condition. Arthritis was induced in a collagen-induced arthritis mouse model using DBA/1JJmsSlc mice and ulcerative colitis was induced by the administration of drinking water containing 3.0% (w/v) DSS. The arthritis/DSS-treated mice developed worse colitis scores compared to that of the other groups of mice. The arthritis/DSS-treated mice did not demonstrate changes in hind foot volumes or in the concentration of matrix metalloproteinase-3 (MMP-3) in the plasma; however, plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α were increased. Our results showed that IL-6 and TNF-α may influence the deterioration effect of colitis in arthritic mice.