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ID PMID Title PublicationDate abstract
29889115 The Fatigue Assessment Scale: quality and availability in sarcoidosis and other diseases. 2018 Sep PURPOSE OF REVIEW: Fatigue is a problem experienced by many patients suffering from chronic diseases, including sarcoidosis patients. It has a substantial influence on patients' quality of life (QoL). It is, therefore, important to properly assess fatigue with a valid and reliable measure. The Fatigue Assessment Scale (FAS) is the only validated self-reporting instrument classifying fatigue in sarcoidosis. The aim of this review was to examine the psychometric properties of the FAS and the diseases and languages in which it has been used. Studies among sarcoidosis patients were also reviewed in terms of outcomes. RECENT FINDINGS: Studies were identified by searching the electronic bibliographic database Pubmed. Search terms used were: FAS and fatigue. Articles were included in the review if the FAS had been used to assess fatigue. RESULTS: Since its introduction, the FAS was used in 26 different diseases or conditions, including stroke, neurologic disorders, rheumatoid arthritis, idiopathic pulmonary fibrosis and sarcoidosis. Its reliability and validity have proved to be good. Unidimensionality has been established. So far, the FAS is available in 20 languages and widely used in sarcoidosis. Digital versions as well as PDFs of various languages are available online (www.wasog.org). SUMMARY: The FAS has good psychometric qualities for the diseases in which it has been examined, including sarcoidosis, and can be used in clinical practice. Healthcare workers can use the FAS to assess fatigue in the management, follow-up and clinical care programmes for their patients consistently across countries, as well as in clinical research.
29714571 Clinical Study Design to Assess Both Short- and Long-term Efficacy in Addition to Group Se 2018 Nov In clinical studies for disorders such as rheumatoid arthritis, type 2 diabetes mellitus, multiple sclerosis, osteoporosis, etc, sometimes the developers need to address safety concerns (eg, cardiovascular risk) in the phase III development, so that a large long-term safety study is needed before registration. This article does not contain any studies with human or animal subjects performed by any of the authors. Aiming for potential regulatory approval with a single confirmatory study, the authors suggest a design that assesses short-term efficacy (eg, signs or symptoms) and long-term efficacy (eg, structure or imaging), as well as safety (eg, major adverse cardiac events), for which a group sequential test is performed applying an alpha spending function. A graphical testing procedure is suggested for the data analysis. The testing procedure controls the family-wise type I error rate. The study may reach all or part of short-term efficacy, long-term efficacy, and/or safety objectives. It is possible to get market approval with a single confirmatory study that assesses short-term efficacy, long-term efficacy, and safety.
29671956 Atherosclerosis and autoimmunity: a growing relationship. 2018 May Atherosclerosis is regarded as one of the leading causes of mortality and morbidity in the world. Nowadays, it seems that atherosclerosis cannot be defined merely through the Framingham traditional risk factors and that autoimmunity settings exert a remarkable role in its mechanobiology. Individuals with autoimmune disorders show enhanced occurrence of cardiovascular complications and subclinical atherosclerosis. The mechanisms underlying the atherosclerosis in disorders like rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, systemic sclerosis and Sjögren's syndrome, seem to be the classical risk factors. However, chronic inflammatory processes and abnormal immune function may also be involved in atherosclerosis development. Autoantigens, autoantibodies, infectious agents and pro-inflammatory mediators exert a role in that process. Being armed with the mechanisms underlying autoimmunity in the etiopathogenesis of atherosclerosis in rheumatic autoimmune disorders and the shared etiologic pathway may result in substantial developing therapeutics for these patients.
29654868 Bee venom therapy: Potential mechanisms and therapeutic applications. 2018 Jun 15 Bee venom is a very complex mixture of natural products extracted from honey bee which contains various pharmaceutical properties such as peptides, enzymes, biologically active amines and nonpeptide components. The use of bee venom into the specific points is so called bee venom therapy, which is widely used as a complementary and alternative therapy for 3000 years. A growing number of evidence has demonstrated the anti-inflammation, the anti-apoptosis, the anti-fibrosis and the anti-arthrosclerosis effects of bee venom therapy. With these pharmaceutical characteristics, bee venom therapy has also been used as the therapeutic method in treating rheumatoid arthritis, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, liver fibrosis, atherosclerosis, pain and others. Although widely used, several cases still reported that bee venom therapy might cause some adverse effects, such as local itching or swelling. In this review, we summarize its potential mechanisms, therapeutic applications, and discuss its existing problems.
29635597 A Step Toward Identifying Sources of Medical Errors: Modeling Standards of Care Deviations 2018 Mar 1 OBJECTIVE: To examine the feasibility of utilizing electronic health records (EHR) to determine a metric for identifying physician diagnostic and treatment deviations in standards of care for different disease states. METHODS: A Boolean-rule-based model compared deviations in standards of care across four disease states: diabetes, cardiovascular disease, asthma, and rheumatoid arthritis. This metric was used to identify the relationship between physician deviations in standards of care procedures, before and after diagnosis, for 76 internal medicine physicians. RESULTS: The Boolean-rule-based model identified patterns of standards of care deviation for the physicians before diagnosis and during treatment. The deviations identified for each of the four disease states were then related to Continuing Medical Education courses that could support further training. The rule-based model was extended and improved by including system and process aspects of medical care that are not specifically related to the physician, yet potentially have an impact on the physician's decision to deviate from the standards of care. CONCLUSION: The Boolean-rule-based approach provided a means to systematically mine EHRs and use these data to assess deviations in standards of care that could identify quality of care issues stemming from system processes or the need for specific CME for a physician.
29574826 Antibody repertoire analysis in polygenic autoimmune diseases. 2018 Sep High-throughput sequencing of the DNA/RNA encoding antibody heavy- and light-chains is rapidly transforming the field of adaptive immunity. It can address key questions, including: (i) how the B-cell repertoire differs in health and disease; and (ii) if it does differ, the point(s) in B-cell development at which this occurs. The advent of technologies, such as whole-genome sequencing, offers the chance to link abnormalities in the B-cell antibody repertoire to specific genomic variants and polymorphisms. Here, we discuss the current research using B-cell antibody repertoire sequencing in three polygenic autoimmune diseases where there is good evidence for a pathological role for B-cells, namely systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis. These autoimmune diseases exhibit significantly skewed B-cell receptor repertoires compared with healthy controls. Interestingly, some common repertoire defects are shared between diseases, such as elevated IGHV4-34 gene usage. B-cell clones have effectively been characterized and tracked between different tissues and blood in autoimmune disease. It has been hypothesized that these differences may signify differences in B-cell tolerance; however, the mechanisms and implications of these defects are not clear.
29411897 The immunopathogenic and immunomodulatory effects of interleukin-12 in periodontal disease 2018 Apr Interleukin 12 (IL-12) is an inflammatory cytokine that promotes the response of the immune system. This cytokine has been implicated as a potent stimulator of several diseases characterized by inflammatory-induced bone destruction, such as rheumatoid arthritis and periodontitis. Yet, the exact role of IL-12 in the development and progress of periodontitis has not been clarified. Several studies have demonstrated a positive correlation between the level of IL-12 and the severity of periodontal destruction. Deletion of IL-12 in mice with periodontitis significantly suppressed the level of bone destruction. Interestingly, next to a role in modulating the pathogenesis, IL-12 also has immunological-regulatory properties. This cytokine induces expression of immunosuppressive molecules, such as indoleamine-pyrrole 2,3-dioxygenase (IDO). Thus, these findings suggest both negative and positive influences of IL-12 in periodontal disease. It is currently proposed that the diversity of action of cytokines is a molecular key which regulates biological development and homeostasis. Accordingly, the actions of IL-12 might be one of the mechanisms that regulate homeostasis of periodontal tissue during and following inflammation. Therefore, this article aims to review both destructive and protective functionalities of IL-12 with an emphasis on periodontal disease.
29392731 Immune modulatory effects of statins. 2018 May Despite major advances in recent years, immunosuppressive regimens for multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and graft-versus-host disease still have major adverse effects and immunomodulation rather than immune paralysis would be desirable. Statins inhibit the rate-limiting enzyme of the l-mevalonate pathway, the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. It was shown that blocking the l-mevalonate pathway reduces inflammation through effects on downstream metabolites of the pathway including farnesylpyrophosphates and geranylgeranylpyrophosphates, which are essential for the attachment of GTPases like RhoA, Rac and Ras to the cell membrane. Therefore, l-mevalonate pathway downstream products play critical roles in the different steps of an immune response including immune cell activation, migration, cytokine production, immune metabolism and survival. This review discusses the relevance of the different metabolites for the immunomodulatory effect of statins and connects preclinical results with data from clinical studies that tested statins for the treatment of different inflammatory diseases.
29141575 The Protective Effects of Extra Virgin Olive Oil on Immune-mediated Inflammatory Responses 2018 BACKGROUND AND OBJECTIVE: The increasing interest in the Mediterranean diet (MeDiet) hinges on the relevant role it plays in inflammatory diseases. Several clinical, epidemiological and experimental evidences suggest that consumption of the MeDiet reduces the incidence of certain pathologies related to oxidative stress, chronic inflammation and immune system diseases such as cancer, atherosclerosis and cardiovascular disease (CVD). These reductions can be partially attributed to extra virgin olive oil (EVOO) consumption which has been described as a key bioactive food because of its high nutritional quality and its particular composition of fatty acids, vitamins and polyphenols. Indeed, the beneficial effects of EVOO have been linked to its fatty acid composition, which is very rich in monounsaturated fatty acids (MUFA), and has moderate saturated and polyunsaturated fatty acids (PUFA). The current knowledge available on the beneficial effects of EVOO and its phenolic compounds, specifically its biological properties and antioxidant capacity against immune-mediated inflammatory responses (atherosclerosis, rheumatoid arthritis, diabetes, obesity, cancer, inflammatory bowel disease or neurodegenerative disease, among others) in addition to its potential clinical applications. CONCLUSION: The increasing body of studies carried out provides compelling evidence that olive polyphenols are potential candidates to combat chronic inflammatory states.
28967793 Fostamatinib for persistent/chronic adult immune thrombocytopenia. 2018 Jan Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by phagocytosis and destruction of autoantibody-coated platelets via spleen tyrosine kinase (Syk)-mediated signal transduction in macrophages. Effectiveness of existing therapies varies, and even leading treatments (e.g., IVIg, splenectomy, rituximab, thrombopoietic agents) do not provide optimal management for a substantial number of patients with chronic ITP. Fostamatinib disodium is an orally-bioavailable investigational agent being developed for treatment of primary persistent/chronic adult ITP. Fostamatinib inhibits FcR-triggered, Syk-dependent cytoskeletal rearrangement during phagocytosis. Promising findings have been described in several autoimmune diseases, including rheumatoid arthritis, and sustained responses with manageable adverse events observed with ongoing treatment in patients with heavily treated chronic ITP. Fostamatinib represents an active therapy targeting a previously unexplored mechanism of ITP pathogenesis.
31284287 Effects of Infliximab against Methotrexate Toxicity in Splenic Tissue via the Regulation o 2018 Methotrexate (MTX), which has been used in clinical practice for approximately 70 years, is still widely employed in the treatment of rheumatoid arthritis (RA), psoriasis, and cancer. Although MTX toxicity causes nephrotoxicity, hepatotoxicity, bone marrow suppression, pulmonary fibrosis, and gastrointestinal damage, previous studies have not addressed splenic toxicity. This is the first study to examine the effectiveness of infliximab (INF) against MTX-induced toxicity in splenic tissues via the regulation of CD3, CD68, and C200R. We investigated the effects of MTX on macrophages and T lymphocytes in the spleen at the molecular level and examined the protective potential of the tumor necrosis factor (TNF)-α antagonist INF against MTX toxicity. Three groups of rats were set up. Group 1 received saline solution only, group 2 a single dose of MTX (20 mg/kg), and group 3 INF (7 mg/kg) before administration of a single dose of MTX (20 mg/kg). All injections were given intraperitoneally. Spleen tissues were removed 5 days after MTX administration and evaluated for CD3, CD68, and CD200R using immunohistochemical staining. Finally, the mean numerical density of CD3+, CD68+, and CD200R+ cells was estimated by a histopathologist using StereoInvestigator 8. MTX increased the numerical densities of CD3+, CD68+, and CD200R+ cells (p < 0.05). We also observed that INF reduced the numerical densities of these cells following MTX administration (p < 0.05). INF may, therefore, be a promising candidate for the prevention of the deleterious effects on spleen tissue of MTX, used in the treatment of RA and cancer.
32232084 Realizing flexible bioelectronic medicines for accessing the peripheral nerves - technolog 2018 Patients suffering from conditions such as paralysis, diabetes or rheumatoid arthritis could in the future be treated in a personalised manner using bioelectronic medicines (BEms) (Nat Rev Drug Discov 13:399-400, 2013, Proc Natl Acad Sci USA 113:8284-9, 2016, J Intern Med 282:37-45, 2017). To deliver this personalised therapy based on electricity, BEms need to target various sites in the human body and operate in a closed-loop manner. The specific conditions and anatomy of the targeted sites pose unique challenges in the development of BEms. With a focus on BEms based on flexible substrates for accessing small peripheral nerves, this paper discusses several system-level technology considerations related to the development of such devices. The focus is mainly on miniaturisation and long-term operation. We present an overview of common substrate and electrode materials, related processing methods, and discuss assembly, miniaturisation and long-term stability issues.
30522694 CD84 cell surface signaling molecule: An emerging biomarker and target for cancer and auto 2019 Jul CD84 (SLAMF5) is a member of the SLAM family of cell-surface immunoreceptors. Broadly expressed on most immune cell subsets, CD84 functions as a homophilic adhesion molecule, whose signaling can activate or inhibit leukocyte function depending on the cell type and its stage of activation or differentiation. CD84-mediated signaling regulates diverse immunological processes, including T cell cytokine secretion, natural killer cell cytotoxicity, monocyte activation, autophagy, cognate T:B interactions, and B cell tolerance at the germinal center checkpoint. Recently, alterations in CD84 have been related to autoimmune and lymphoproliferative disorders. Specific allelic variations in CD84 are associated with autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. In chronic lymphocytic leukemia, CD84 mediates intrinsic and stroma-induced survival of malignant cells. In this review, we describe our current understanding of the structure and function of CD84 and its potential role as a therapeutic target and biomarker in inflammatory autoimmune disorders and cancer.
30527218 JAK-STAT inhibitors for the treatment of immunomediated diseases. 2019 May 3 The Janus kinase (JAK) pathway is implicated in the pathogenesis of many inflammatory and autoimmune diseases including rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease. There are a lot of proinflammatory cytokines involved in such diseases using this pathway to transduce intracellular signals. In the last years, JAK inhibitors (jakinibs) have appeared with a great success, showing that these kinds of drugs have a great applicability in clinical practice. Tofacitinib and baricitinib, the first jakinibs approved for the treatment of RA, are being investigated also for treating other autoimmune systemic diseases. Likewise, other jakinibs are in several phases of development. This review analyses the safety and clinical efficacy of the jakinibs, starting with the classics and continuing with next-generation jakinibs.
30258504 Tocilizumab in Large Vessel Vasculitis - Different Routes of Administration. 2018 BACKGROUND: Tocilizumab is increasingly used in the treatment of large vessel vasculitis with recent approval for giant cell arteritis. OBJECTIVE: To determine the efficacy and safety of tocilizumab in large vessel vasculitis in a real-life setting using different routes of administration. METHODS: Retrospective analysis of consecutive patients at a tertiary rheumatology department who received tocilizumab for large vessel vasculitis. RESULTS: A total of 11 patients were treated with tocilizumab (8 giant cell arteritis, 2 large vessel vasculitis associated with rheumatoid arthritis, 1 Takayasu arteritis) after a median of 2 other steroid-sparing agents (range 1-4). Of these, 9 received tocilizumab as salvage therapy for active vasculitis and 2 due to the toxicity of their former steroid-sparing medication. After a mean follow-up of 23 months 7 patients were in remission as to vasculitis under a mean prednisolone dose of 1.7 ± 1.5 mg; one patient relapsed after long term remission having discontinued tocilizumab for elective surgery; one patient stopped tocilizumab after attributable infectious complications, and two patients died: one due to complications of vascular surgery, probably not attributable to tocilizumab; and the other due to sepsis secondary to sigmoiditis. Only 3 relapses occurred under continuous tocilizumab treatment. In all these 3 cases, renewed remission could be achieved by switching from subcutaneous (162 mg qw) to intravenous tocilizumab (8mg/kg q4w). CONCLUSION: Tocilizumab is efficacious in patients with large vessel vasculitis in a real-life situation. Safety appears to be acceptable, but infectious complications have to be considered. Intravenous tocilizumab may be used in patients who relapse under subcutaneous application.
30133608 Gluten and Neuroimmunology. Rare association with Myasthenia Gravis and Literature Review. 2018 Apr As the celiac disease (CD), the non-celiac gluten sensitivity (NCGS) has also been associated with several autoimmune manifestations. It is rarely associated with myasthenia gravis (MG). This paper shall introduce the case of a young female patient, initially presenting a peripheral neuropathy framework. During clinical and neurological follow-up, she began to present symptoms of various immune-mediated morbidities. Diseases related to gluten represent a clinical spectrum of manifestations with a trigger in common, the ingestion of gluten. CD is the most well-known and serious disease of the spectrum, also called gluten-sensitive enteropathy. The NCGS is diagnosed from clinical evidence of improvement in symptoms followed by a Gluten Free Diet (GFD) in patients without signs of enteropathy in duodenal biopsy. There are indications that, although rare, with a prevalence of 1 in 5000, myasthenia gravis (MG) may occur more often when CD is also present. Between 13 to 22% of the patients with MG have a second autoimmune disorder. However, it is often associated with dermatomyositis or polymyositis, lupus erythematosussystemic lupus erythematosus, Addison's disease, Guillain-Barré syndrome and juvenile rheumatoid arthritis. Thus, the symptoms of neuromuscular junction involvement may give a diagnostic evidence of this rare association.
30108582 The Therapeutic and Pathogenic Role of Autophagy in Autoimmune Diseases. 2018 Autophagy is a complicated cellular mechanism that maintains cellular and tissue homeostasis and integrity via degradation of senescent, defective subcellular organelles, infectious agents, and misfolded proteins. Accumulating evidence has shown that autophagy is involved in numerous immune processes, such as removal of intracellular bacteria, cytokine production, autoantigen presentation, and survival of lymphocytes, indicating an apparent and important role in innate and adaptive immune responses. Indeed, in genome-wide association studies, autophagy-related gene polymorphisms have been suggested to be associated with the pathogenesis of several autoimmune and inflammatory disorders, such as systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. In addition, conditional knockdown of autophagy-related genes in mice displayed therapeutic effects on several autoimmune disease models by reducing levels of inflammatory cytokines and autoreactive immune cells. However, the inhibition of autophagy accelerates the progress of some inflammatory and autoimmune diseases via promotion of inflammatory cytokine production. Therefore, this review will summarize the current knowledge of autophagy in immune regulation and discuss the therapeutic and pathogenic role of autophagy in autoimmune diseases to broaden our understanding of the etiopathogenesis of autoimmune diseases and shed light on autophagy-mediated therapies.
30105021 The Coagulation Factors Fibrinogen, Thrombin, and Factor XII in Inflammatory Disorders-A S 2018 BACKGROUND: The interaction of coagulation factors has been shown to go beyond their traditional roles in hemostasis and to affect the development of inflammatory diseases. Key molecular players, such as fibrinogen, thrombin, or factor XII have been mechanistically and epidemiologically linked to inflammatory disorders like multiple sclerosis (MS), rheumatoid arthritis (RA), and colitis. OBJECTIVES: To systematically review the evidence for a role of coagulation factors, especially factor XII, fibrinogen, and thrombin in inflammatory disorders like MS, RA, and bowel disorders. METHODS: A systematic literature search was done in the PubMed database to identify studies about coagulation factors in inflammatory diseases. Original articles and reviews investigating the role of the kallikrein-kinin and the coagulation system in mouse and humans were included. RESULTS: We identified 43 animal studies dealing with inflammatory disorders and factors of the kallikrein-kinin or the coagulation system. Different immunological influences are described and novel molecular mechanisms linking coagulation and inflammation are reported. CONCLUSION: A number of studies have highlighted coagulation factors to tip the balance between hemostasis and thrombosis and between protection from infection and extensive inflammation. To optimize the treatment of chronic inflammatory disorders by these factors, further studies are necessary.
30099999 Immunosuppressive/Autoimmune Disorders. 2018 Sep Autoimmune disorders are a category of diseases in which the immune system attacks healthy cells as a result of a dysfunction of the acquired immune system. Clinical presentation and diagnosis are disease specific and often correspond with the degree of inflammation, as well as the systems involved. Treatment varies based on the specific disease, its stage of presentation, and patient symptoms. The primary goal of treatment is to decrease inflammation, minimize symptoms, and lessen the potential for relapse. Graves disease, Hashimoto thyroiditis, rheumatoid arthritis, Crohn disease, ulcerative colitis, systemic lupus erythematosus, and multiple sclerosis are discussed in this article.
30075502 Management of multiple neurological complications in mixed connective tissue disease: A ca 2018 Aug RATIONALE: Mixed connective tissue disease (MCTD) refers to an overlapping condition of different autoimmune disorders such as systemic lupus erythematosus, cutaneous systemic sclerosis, rheumatoid arthritis, polymyositis, and dermatomyositis. However, MCTD manifesting as transverse myelitis is extremely rare. Herein, we report a case of MCTD with both central and peripheral nervous system involvement. PATIENT CONCERNS: We describe and discuss the clinical findings and management of a 36-year-old man presented with a 2-week history of sudden bilateral lower-limb paralysis and dysuresia. Further investigation of his medical history showed a 6-month history of autoimmune symptoms. DIAGNOSES: The patient was diagnosed with MCTD, transverse myelitis, mononeuritis multiplex, and multiple lacunar infarctions. INTERVENTIONS: A combination of low-dose methylprednisolone (40 mg/d) and hydroxychloroquine sulfate (400 mg/d) was administered. OUTCOMES: After treatment, the symptoms were significantly improved. The patient recovered well after 1 year follow-up and the sequela was urinary incontinence and grade 4/5 lower-extremity muscle strength. LESSONS: MCTD with multiple neurological complications is extremely rare and poses diagnostic and therapeutic challenges. Our experience suggests a combination of low-dose corticosteroids and hydroxychloroquine sulfate may be an effective therapeutic approach.