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ID PMID Title PublicationDate abstract
30487596 The role of Ca(2+) in acid-sensing ion channel 1a-mediated chondrocyte pyroptosis in rat a 2019 Apr Rheumatoid arthritis is an autoimmune disease with a poor prognosis. Pyroptosis is a type of proinflammatory programmed cell death that is characterised by the activation of caspase-1 and secretion of the proinflammatory cytokines interleukin (IL)-1β/18. Previous reports have shown that pyroptosis is closely related to the development of some autoimmune diseases, such as rheumatoid arthritis. The decrease in the pH of joint fluid is a main pathogenic feature of RA and leads to excessive apoptosis in chondrocytes. Acid-sensitive ion channels (ASICs) are extracellular H(+)-activated cation channels that mainly influence Na(+) and Ca(2+) permeability. In this study, we investigated the role of Ca(2+) in acid-sensing ion channel 1a-mediated chondrocyte pyroptosis in an adjuvant arthritis rat model. The expression of apoptosis-associated speck-like protein, NLRP3, caspase-1, ASIC 1a, IL-1β and IL-18 was upregulated in the joints of rats compared with that in normal rats, but the expression of Col2a in cartilage was decreased. However, these changes were reversed by amiloride, which is an inhibitor of ASIC1a. Extracellular acidosis significantly increased the expression of ASIC1a, IL-1β, IL-18, ASC, NLRP3 and caspase-1 and promoted the release of lactate dehydrogenase. Interestingly, Psalmotoxin-1 (Pctx-1) and BAPTA-AM inhibited these effects. These results indicate that ASIC1a mediates pyroptosis in chondrocytes from AA rats. The underlying mechanism may be associated with the ability of ASIC1a to promote [Ca(2+)](i) and upregulate the expression of the NLRP3 inflammasome.
29054585 [Influence of epigenetic in Sjögren's syndrome]. 2018 May Sjögren's syndrome (SS) is a systemic autoimmune epithelitis with a major female incidence, and characterized by a dry syndrome, impaired quality of life, visceral involvement, and lymphoma for the most aggressive cases. During this process, epithelial cells acquire the capacity to produce cytokines, chemokines, and autoantigens which can in turn be presented to the immune system. Consequently, this epithelitis is accompanied by lymphocytic infiltrations leading to the formation of pseudo-follicles in which self-reactive B lymphocytes are present. The recent integration of genomic and especially of epigenomic data, which make it possible to analyze the different cellular partners, opens new perspectives and allows to a better understanding of this complex and still incurable disease.
30544414 Serum amyloid A1 (SAA1) gene polymorphisms in Japanese patients with adult-onset Still's d 2018 Dec Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder in which inflammasome activation plays a pathophysiological role. In view of the inflammatory nature of AOSD, we investigated whether serum amyloid A (SAA) gene polymorphisms affect the susceptibility of patients with AOSD.Eighty-seven Japanese patients with AOSD and 200 healthy Japanese subjects were recruited in this study. The genotypes of the -13C/T SNP in the 5'-flanking region of the SAA1 gene (rs12218) and two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined using polymerase chain reaction fragment length polymorphism (PCR-RFLP) assay in all subjects. In AOSD patients, exons 1, 2, 3, and 10 of the MEFV gene were also genotyped by direct sequencing.The frequency of the SAA1.3 allele was increased in AOSD patients compared with that in healthy subjects (43.1% versus 37.5%), but the difference was not significant. The -13T allele was more frequently observed in AOSD patients than in healthy subjects (50.6% versus 41.0%, P = .0336). AOSD patients with the -13T allele had been treated with immunosuppressants more frequently than those without this allele. MEFV mutations were detected in 49 patients with AOSD (49/87, 57.3%). AOSD patients with MEFV variants frequently exhibit macrophage activation syndrome, but the difference was not significant (34.7% versus 18.4%, P = .081). Also, there was no significant difference in SAA1 -13C/T allele frequency between AOSD patients with and without MEFV mutations.Our data shows a significant association between T allele of rs12218 and AOSD in Japanese population.
30170935 An unusual manifestation of Sjögren syndrome encephalitis. 2019 Feb Sjögren syndrome (SS) is a systemic inflammatory and autoimmune disease characterized by systemic disorders of the exocrine glands, predominantly the salivary and lacrimal glands. Here, we report a 4-year-old boy who presented with the repetition of generalized tonic-clonic seizures for 1-2 min. Initially, he was diagnosed with idiopathic autoimmune encephalitis and was treated with steroids. He was eventually diagnosed with SS based on the examination results, such as inflammatory cell infiltration into the minor salivary glands and positive serum anti-SSA/Ro antibody. Although central nervous system complications are rare in pediatric SS, this condition should be considered in the differential diagnosis when a patient presents with idiopathic autoimmune encephalitis of unknown cause. Furthermore, SS can occur in relatively young children and can present without imaging abnormalities.
30572133 Lymphomagenesis in Sjögren's syndrome: Predictive biomarkers towards precision medicine. 2019 Feb Sjögren's syndrome (SS) is characterized by B cell hyperactivity documented by the production of plethora of autoantibodies and a strong tendency for NHL of B cell origin. Classical predictors of lymphoma have been already proposed and proved their validity, including clinical, serological and histopathologic biomarkers. The process of lymphomagenesis is multistep and encompasses mechanisms of antigen driven selection of the BCR with RF activity and various genetic contributors implicated in B cell proliferation, cell growth and cell cycle control, enhanced by a complex milieu of cytokines and trophic agents that are abundant within the inflammatory lesion of minor salivary glands of SS patients. Extensive efforts in the basic research field have revealed several novel biomarkers for lymphoma prediction while the major cellular and molecular mechanisms of evolutionary transition of B cells towards malignancy are under investigation. In this review, we present the current data regarding the newly proposed biomarkers for SS associated lymphoma prediction and a hypothetical model of lymphomagenesis based on the emerging data.
29269680 Severe Adult-onset Still Disease with Constrictive Pericarditis and Pleuritis That Was Suc 2018 Apr 1 Adult-onset Still disease (AOSD) is a systemic inflammatory disease characterized by fever, arthritis and rash. Corticosteroids represent a promising therapeutic option for AOSD; however, some resistant cases require immunosuppressants and biologic agents. We herein report the case of a 29-year-old Japanese man with severe AOSD, accompanied by constrictive pericarditis (CP) and pleuritis. Although 2 courses of steroid pulse and subsequent high-dose of prednisolone and cyclosporine A improved the patient's CP and pleuritis, his fever and inflammatory responses persisted. Tocilizumab (TCZ) was added to his treatment, which resulted in a rapid remission. This case suggests the usefulness of TCZ in the treatment of severe AOSD with CP and pleuritis.
29093421 Hypertrophic Pachymeningitis in Sjögren's Syndrome. 2018 Feb 1 Although central nervous system manifestations seem common in primary Sjögren's syndrome, hypertrophic pachymeningitis is rare. We herein describe a case of Sjögren's syndrome that was associated with hypertrophic pachymeningitis. Sjögren's syndrome should be considered as a cause of hypertrophic pachymeningitis.
26052802 Combined disease with pulmonary arterial hypertension and pulmonary venous hypertension re 2018 Jan A 49-year-old woman with primary Sjögren syndrome initially developed pulmonary venous hypertension (PVH) due to heart failure with preserved ejection fraction. Endomyocardial biopsy specimens showed mild myocardial fibrosis. Pulmonary arterial hypertension (PAH) was revealed after the treatment with diuretics. During the treatment for PAH using upfront combination with pulmonary vasodilators and immunosuppressants, the patient developed combined disease with PAH and PVH. A careful hemodynamic assessment is necessary in such cases.
29132785 Nonrheumatoid Arthritis of the Hand. 2018 Jan Arthropathy of the hand is commonly encountered. Contributing factors such as aging, trauma, and systemic illness all may have a role in the evolution of this pathology. Besides rheumatoid arthritis, other diseases affect the small joints of the hand. A review of nonrheumatoid hand arthropathies is beneficial for clinicians to recognize these problems.
29389830 Emergence and treatment of chikungunya arthritis. 2018 May PURPOSE OF REVIEW: To review the emergence, clinical features, pathogenesis, and treatment of acute chikungunya (CHIK) fever and chronic CHIK arthritis. RECENT FINDINGS: Since 2004, CHIK, an arboviral infection, has spread throughout the world, infecting millions of people. The illness occurs in two phases: an acute viremic infection followed by chronic arthritis. In less developed countries, there are limited resources and effective treatment. For acutely ill CHIK fever patients, management is symptomatic. The treatment of chronic CHIK arthritis should be determined by an understanding of pathogenesis. Is chronic CHIK arthritis a persistent viral infection or a postinfectious inflammatory process? Multiple proinflammatory cytokines, chemokines, and growth factors have been identified in chronic CHIK arthritis. Attempts to isolate CHIK virus from synovial fluid have been unsuccessful. Given pathogenetic similarities (as well as differences) compared with rheumatoid arthritis and the painful, disabling nature of the arthritis, it is not surprising that disease-modifying antirheumatic drugs such as methotrexate have begun to be used. SUMMARY: CHIK infection has emerged with major arthritic epidemics for which evidence-based therapy is limited. But there is an opportunity to improve the treatment of chronic CHIK arthritis and, from this disease, to gain understanding of the pathogenesis and treatment of inflammatory arthritis more generally.
29792851 Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexua 2018 Aug Collagen-induced arthritis (CIA) is a frequently used animal model of rheumatoid arthritis, human autoimmune disease that exhibits clear sex bias in incidence and clinical course. Female Dark Agouti rats immunized for CIA showed also greater incidence and higher arthritic score than their male counterparts. The study investigated sex differences in mechanisms controlling the primary immune responses in draining lymph nodes (dLNs), as a factor contributing to this dimorphism. The higher frequencies of CD4 + CD25 + Foxp3- cells, presumably activated effector T (Teff) cells, and IL-17+, IFN-γ + and IL-17 + IFN-γ + T cells were found in female compared with male rat dLNs. However, the frequency of CD4 + CD25 + Foxp3+ T regulatory cells (Treg) did not differ between sexes. Thus, CD4+ Teff cells/Treg ratio, and IL-17+ T cells/Treg and IFN-γ + T cells/Treg ratios were higher in female than in male rats, and among them was found lower frequency of PD-1+ cells. This suggested less efficient control of (auto)immune Th1/Th17 cell responses in female rat dLNs. On the contrary, the frequency of IL-4+ T cells was lower in female than in male rat dLNs. Consistently, the ratio of serum levels of collagen-specific IgG2a (IFN-γ-dependent, with an important pathogenic role in CIA) and IgG1 (IL-4-dependent) was shifted towards IgG2a in female compared with male rats. As a whole, the study suggests that sexual dimorphism in the control of T cell activation/polarization could contribute to sex bias in the susceptibility to CIA. Moreover, the study advises the use of animals of both sexes in the preclinical testing of new drugs for rheumatoid arthritis.
31643573 Rituximab. 2012 Rituximab is a chimeric mouse/human monoclonal antibody to CD20 a cell surface antigen found on pre-B and mature B lymphocytes and which is approved for use in non-Hodgkin lymphoma and chronic lymphocytic leukemia as well as in several autoimmune conditions, including rheumatoid arthritis and Wegener granulomatous. Rituximab has been linked to many cases of severe and even fatal liver injury as a result of reactivation of inactive or previously resolved hepatitis B.
29622302 Applied Bayesian Methods in the Rheumatic Diseases. 2018 May The use of applied Bayesian methods is increasing in rheumatology. Using the Bayes theorem, past evidence is updated with new data. Preexisting data are expressed as a prior probability distribution or prior. New observations are expressed as a likelihood. Through explicit incorporation of preexisting data and new data, this process informs how this new information should change the way we think. In this article, the authors highlight the use of applied Bayesian methods in the study of rheumatic diseases.
29660305 Temporomandibular Joint Reconstruction in Patients With Autoimmune/Connective Tissue Dis 2018 Aug PURPOSE: To evaluate clinical outcomes in patients with autoimmune or connective tissue (CT) disease undergoing temporomandibular joint (TMJ) reconstruction. MATERIALS AND METHODS: Patients were divided into 2 groups based on type of TMJ reconstruction. Patients in group 1 (n = 9) underwent autogenous reconstruction and had a diagnosis of rheumatoid arthritis (5), lupus arthritis (1), and psoriatic arthritis (3). Patients in group 2 (n = 2l) had alloplastic reconstruction with a patient-fitted total joint prosthesis (TMJ Concepts, Ventura, CA) and had a diagnosis of rheumatoid arthritis (15), lupus (3), and psoriatic arthritis (3). Standardized clinical and radiographic examinations were performed before surgery, immediately after surgery, and at longest follow-up after surgery (T3). RESULTS: Group l showed no meaningful improvement in maximal opening without pain, a decrease in lateral excursions, minimal decrease in TMJ pain, and a 32% relapse of chin projection at point B at T3. Average postsurgery follow-up time was 58 months. Postsurgical ankylosis was seen in 22% of patients. In contrast, group 2 showed a statistically meaningful decrease in subjective TMJ pain and lateral excursive movements and improvement in jaw function, diet, maximal incisal opening without pain, and only 5% showed a relapse at point B at T3. Average postsurgical follow-up in this group was 78 months. CONCLUSIONS: Improved treatment outcomes were obtained with alloplastic TMJ total joint reconstruction compared with autogenous TMJ reconstruction in patients with autoimmune or CT disease.
31171312 Oral treatment options for AS and PsA: DMARDs and small-molecule inhibitors. 2018 Jun Spondyloarthritis (SpA) represents a group of common diseases that share a number of characteristic clinical manifestations including peripheral arthritis, spondylitis, enthesitis, and dactylitis. Additionally, they can often be associated with extra-articular manifestations including psoriasis, anterior uveitis, and inflammatory bowel disease. The two most widely studied clinical phenotypes are ankylosing spondylitis and psoriatic arthritis. Although a number of biologic agents have been shown to be highly effective in treating these conditions, rheumatologists must generally initiate therapy with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) such as methotrexate and sulfasalazine. The use of these medications stems from our experience in rheumatoid arthritis, and there is a paucity of convincing clinical data supporting their use in SpA. More recently, new targeted synthetic DMARDs have become available and are a welcome addition to the management of these conditions. Through this review, we hope to highlight the evidence behind available treatment options on the various domains of these diseases including synovitis, enthesitis, dactylitis, and spondylitis. We also discuss the available evidence regarding co-medication of csDMARDs with biologic agents.
30092352 Inhibition of C5a prevents IL-1β-induced alternations in rat synoviocytes in vitro. 2018 Oct C5a is an important pro-inflammatory peptide involved in complement activation, membrane attack complex formation, immune cell chemotaxis, and allergic responses. Osteoarthritis is a disease characterized by degenerative changes in articular cartilage. It has recently been found that inflammatory responses play an important role in the pathogenesis of osteoarthritis and also in rheumatoid arthritis, where dysfunctional synoviocytes are involved. We performed a series of studies to verify our hypothesis that inhibition of C5a would prevent IL-1β-induced alternations in rat synoviocytes. In vitro studies were performed with RSC-364 cells to examine the role of C5a in the function of synoviocytes. RSC-364 cells (a rat derived synovial cell line) were treated with IL-1β, IL-1β+siC5a, IL-1β+PMX205 that is antagonist of C5aR, or left untreated. Cell cycle, proliferation, apoptosis, invasion, as well as levels of C5a, IL-17A and TNF-α expression were evaluated. We found that IL-1β could significantly increase the proliferation and invasion capabilities of RSC-364 cells, as well as of C5a IL-17A and TNF-α expression. In contrast, inhibition of C5a by siRNA or application of antagonist of C5aR PMX205 reversed the IL-1β-induced changes in C5a expression, cell cycle, proliferation, apoptosis, invasion, and cytokines releases. Taken together, our study results suggest that IL-1β can increase C5a expression in RSC-364 cells, and that C5a exerts a proinflammatory effect in RSC-364 cells. Inhibition of C5a might represent a new strategy for treating rheumatoid arthritis.
30122906 Patients' and nurses' preferences for autoinjectors for rheumatoid arthritis: results of a 2018 PURPOSE: This survey investigated patients' and nurses' preferences among four different autoinjectors used for subcutaneous delivery of medication for rheumatoid arthritis (RA). METHODS: In a multinational survey in five countries, 200 patients with RA and 100 nurses training patients on the use of autoinjectors participated in face-to-face interviews. Respondents were asked to rate the importance of eleven autoinjector attributes and to compare the autoinjectors for etanercept (Enbrel(®), MyClic(®) autoinjector), adalimumab (Humira(®), Humira pen), and an etanercept biosimilar (Benepali(®), Molly(®) autoinjector) with a demonstration autoinjector for a new etanercept biosimilar - Erelzi(®) (SensoReady(®) autoinjector). RESULTS: Easy grip and ease of performing self-injection were the most important attributes identified by both groups. Overall, 79% of the patients rated the SensoReady autoinjector easier to use than their currently used injection device (86% of MyClic users, 84% of Humira pen users, and 63% of Molly users). In the patient survey, the SensoReady performed better than the other autoinjectors on the attributes visual feedback after completion of injection, easy to grip, and convenient shape. Nurses also rated the SensoReady easier to use than the MyClic (95%), Humira pen (97%), or Molly (91%). When asked which autoinjector they would recommend to a patient with RA who had not used an autoinjector before, 81% of patients and 90% of nurses selected the SensoReady. CONCLUSION: Both patients and nurses perceived the SensoReady to be easier to use compared with other available injection devices. The main reasons for this preference were the buttonless injection, 360° viewing window for feedback (visual confirmation of dose injection), and convenient triangular shape making the injection device easy to grip. Patients and nurses were most likely to recommend the SensoReady autoinjector over other autoinjectors to patients with RA.
30051260 Autoimmunity in 2017. 2018 Dec The number of peer-reviewed articles published during the 2017 solar year and retrieved using the "autoimmunity" key word increased significantly compared to 2016 while maintaining a stable share within the immunology field, following years with alternated fortunes. A detailed arbitrary analysis of the published articles in leading immunology and autoimmunity journals provides a privileged viewpoint on the current trends of research from both basic and clinical studies. Indeed, we are observing that major steps forward are found for rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, among others. In particular, the new data on pregnancy success in lupus or biomarkers in systemic sclerosis are believed to change our management of these systemic conditions. In the case of rheumatoid arthritis, we have obtained data with significant implications in the understanding of the disease pathogenesis (as in the case of platelets), disease phenotyping, and new treatment options. Furthermore, the exponential growth of treatment options for cancer based on immune checkpoint modulation is paralleled by the need to address the potential autoimmunity side effects while taking advantage of new information obtained in paraneoplastic autoimmune conditions. Cumulatively, 2017 has been a very exciting year for autoimmune diseases, and we foresee that most of the data discussed herein will be followed by more extensive studies in the upcoming months.
29683362 Immunogenicity of biologic therapies: causes and consequences. 2018 Jun Antibodies or fusion proteins termed biologics allow the targeted therapy of diseases. Many of these agents have proven superior efficacy and safety to conventional therapies, and subsequently revolutionized the management of numerous chronic diseases. Repetitive administration of these protein-based therapeutics to immunocompetent patients elicit immune responses in the form of Anti Drug Antibodies (ADAs), which in turn impact their pharmacological properties and may trigger adverse events. Areas covered: Structural characteristics determining the immunogenicity of biologics are reviewed along with strategies to minimize it. Next, the different types of treatment-emerging ADAs, their potential clinical implications, and assays to detect them are addressed. Emphasis is put on the review of data on the immunogenicity of different types of biologics across numerous indications. Finally, practical considerations are discussed on how to manage patients with issues around the immunogenicity of their biologic treatment. Expert commentary: Immunogenicity is a clinically relevant criterion when selecting a biologic. Besides intrinsic properties of the agent (namely its structure), its respective mode of action, dosing regimen, comedication, and the indication treated must be considered. ADA detection assays need to be standardized to improve comparability of available data and to allow clinical decision-making.
29849657 Miliary Histoplasmosis in a Patient with Rheumatoid Arthritis. 2018 Miliary histoplasmosis is a rare presentation that may mimic miliary tuberculosis. We report a case of miliary histoplasmosis in a 52-year-old male who was being treated with hydroxychloroquine, methotrexate, and sulfasalazine for his rheumatoid arthritis and presented to the emergency department with shortness of breath and fevers. Computed tomography (CT) chest revealed miliary pulmonary nodules. Urine Histoplasma antigen and serum Histoplasma antigen were negative; however, Coccidioides immitis complement immunofixation assay and Coccidioides IgM were positive. The patient was initiated on treatment for pulmonary coccidioidomycosis and immunosuppression was held. However, a few days later, Histoplasma capsulatum was isolated from cultures from bronchoscopy. This case highlights the difficulty in diagnosing histoplasmosis in immunocompromised patients and the importance of having a broad differential diagnosis for miliary pulmonary nodules. Tissue culture and histopathology remain the gold standard for the diagnosis of histoplasmosis. Further research needs to be conducted to determine the optimal duration of histoplasmosis treatment in immunocompromised patients.