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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
27525064 Elucidating novel disease mechanisms in severe asthma. 2016 Jul Corticosteroids are broadly active and potent anti-inflammatory agents that, despite the introduction of biologics, remain as the mainstay therapy for many chronic inflammatory diseases, including inflammatory bowel diseases, nephrotic syndrome, rheumatoid arthritis, chronic obstructive pulmonary disease and asthma. Significantly, there are cohorts of these patients with poor sensitivity to steroid treatment even with high doses, which can lead to many iatrogenic side effects. The dose-limiting toxicity of corticosteroids, and the lack of effective therapeutic alternatives, leads to substantial excess morbidity and healthcare expenditure. We have developed novel murine models of respiratory infection-induced, severe, steroid-resistant asthma that recapitulate the hallmark features of the human disease. These models can be used to elucidate novel disease mechanisms and identify new therapeutic targets in severe asthma. Hypothesis-driven studies can elucidate the roles of specific factors and pathways. Alternatively, 'Omics approaches can be used to rapidly generate new targets. Similar approaches can be used in other diseases.
28955915 Effect of dietary fish oil on mouse testosterone level and the distribution of eicosapenta 2016 Sep Low levels of serum testosterone are characteristically associated with diabetes, coronary atherosclerosis, obstructive sleep apnea, rheumatoid arthritis, and chronic obstructive pulmonary disease. Testosterone replacement therapy is effective against many of these disorders, indicating the importance of maintaining a healthy testosterone level. In this study, we investigated the effects of fish oil on murine testosterone metabolism and analyzed the dynamics of relevant lipids in testes by matrix-assisted laser desorption ionization mass spectrometry imaging. Testosterone was upregulated in mice that received fish oil. In the testicular interstitium, eicosapentaenoic acid-containing phosphatidylcholine was distributed characteristically. These data suggest that eicosapentaenoic acid is involved in testosterone metabolism.
27228636 Infections and Biological Therapy in Patients with Rheumatic Diseases. 2016 Mar Long-term extension studies and observational drug registers have revealed an increased risk of serious infections in patients treated with anti-tumor necrosis factor agents, particularly infliximab, etanercept and adalimumab. The same may be true for the newer biological drugs rituximab, tocilizumab and abatacept, although this has yet to be confirmed by long-term observational studies. We review the risk of tuberculosis, herpes zoster and other opportunistic infections, and the recommendations for screening for tuberculosis and hepatitis B and C infections in patients with rheumatoid arthritis, with the aim of informing patients and encouraging greater awareness among physicians.
29201698 Drug-induced Liver Disease in Patients with Diabetes Mellitus. 2015 Jul The study presented here was accomplished to assess the course of drug-induced liver diseases in patient's rheumatoid arthritis receiving long-term methotrexate therapy. Diabetes mellitus was revealed as the most significant risk factor. The combination of diabetes mellitus with other risk factors (female sex) resulted in increased hepatic fibrosis, degree of hepatic encephalopathy and reduction of hepatic functions. The effectiveness and safety of ursodeoxycholic acid and cytolytic type-with S-Adenosyl methionine was also evaluated. ABBREVIATIONS: 13C-MBT: 13C-methacetin breath test; ALT: alanine aminotransferase; AP: alkaline phosphatase; AST: aspartic transaminase; DILD: drug-induced liver disease; DM: diabetes mellitus; HE: hepatic encephalopathy; HFM: hepatic functional mass; SAMe: S-Adenosyl methionine; UDCA: ursodeoxycholic acid. HOW TO CITE THIS ARTICLE: Iryna K, Helen M, Elena S. Drug-induced Liver Disease in Patients with Diabetes Mellitus. Euroasian J Hepato-Gastroenterol 2015;5(2):83-86.
25693763 Platelet serotonin modulates immune functions. 2016 This short review addresses immune functions of platelet serotonin. Platelets transport serotonin at a high concentration in dense granules and release it upon activation. Besides haemostatic, vasotonic and developmental modulation, serotonin also influences a variety of immune functions (mediated by different serotonin receptors). First, platelet serotonergic effects are directed against invading pathogens via activation and proliferation of lymphocytes, modulation of cytokine release, and recruitment of neutrophils to sites of acute inflammation by induction of selectin expression on endothelial cells. Second, serotonin levels are elevated in autoimmune diseases, such as asthma or rheumatoid arthritis, and during tissue regeneration after ischemia of myocardium or brain. Specific antagonism of serotonin receptors appears to improve survival after myocardial infarction or sepsis and to attenuate asthmatic attacks in animal models. It will be of great clinical relevance if these findings can be translated into human applications. In conclusion, targeting immune modulatory effects of platelet serotonin may provide novel therapeutic options for common health problems.
26040207 Functional and genetic diversity of leukocyte immunoglobulin-like receptor and implication 2015 Nov Human leukocyte immunoglobulin-like receptors (LILR) are a family of 11 functional genes encoding five activating (LILRA1, 2, 4-6), five inhibitory (LILRB1-5) and one soluble (LILRA3) form. The number of LILR genes is conserved among individuals, except for LILRA3 and LILRA6, which exhibit copy-number variations. The LILR genes are rapidly evolving and showing large interspecies differences, making it difficult to analyze the functions of LILR using an animal model. LILRs are expressed on various cells such as lymphoid and myeloid cells and the expression patterns are different from gene to gene. The LILR gene expression and polymorphisms have been reported to be associated with autoimmune and infectious diseases such as rheumatoid arthritis and cytomegalovirus infection. Although human leukocyte antigen (HLA) class I is a well-characterized ligand for some LILRs, non-HLA ligands have been increasingly identified in recent years. LILRs have diverse functions, including the regulation of inflammation, immune tolerance, cell differentiation and nervous system plasticity. This review focuses on the genetic and functional diversity of the LILR family.
27786419 Medical arthroscopy: A tool for diagnosis and research in rheumatology. 2017 Feb Arthroscopy is an important diagnostic procedure which can be used in rheumatology practice to provide direct visualization of the joint cavity, permitting macroscopic evaluation of the synovium, sampling for histopathologic and microbiologic examination and the potential therapeutic benefit of lavage. The term 'medical arthroscopy' is used here to refer to arthroscopy performed by rheumatologists for these purposes. This term differentiates arthroscopy performed by orthopedic surgeons for structural interventions such as meniscal debridement and ligament repair. Medical arthroscopy finds a place in rheumatology as an aid to diagnosis, to confirm the presence of synovitis when not expected, to provide histologic or microbiologic diagnosis, and potential stratification for therapy, for example in rheumatoid arthritis, as well as a range of other research purposes. It is performed with local anesthetic using a small bore arthroscope, most usually inserted into the knee, although the wrist and metacarpophalangeal joints may also be inspected in this way. In experienced hands it is well tolerated, safe and complications are comparable to those reported by orthopedic surgeons.
27441391 Vitamin D: not just bone, but also immunity. 2016 Dec Vitamin D should not be considered only as a vitamin. It has a relevant role in many functions of body regulation, both skeletal and extra skeletal and this makes vitamin D an essential element for a healthy status. This is well explained by a ubiquitous presence of vitamin D receptors. Nowadays extra skeletal effects have a more interesting impact in medical practice. The paracrine and autocrine action of vitamin D has a pivotal role for these effects. The activation of the cellular transcriptional process leads to the expression of beta-defensin and cathelicidin, activating the Th1 pathway, related to innate immunity against bacteria. The action of vitamin D is also related to adaptive immunity with a Th2 response and production of anti-inflammatory cytokines like interleukins 4 and 5, and with Th17 and B-lymphocyte suppression. Vitamin D deficiency could have an unfavorable effect on both healthy and ill subjects. It is well-known that many autoimmune diseases like systemic lupus erythematosus and rheumatoid arthritis are influenced by vitamin D deficiency, and this is especially true for disease activity. Several other pathologies are influenced by the levels of vitamin D, such as diabetes mellitus type 1: an adequate intake of vitamin D can reduce the risk to develop this disease. The same applies to asthma and multiple sclerosis. It is very important to make a point about the deficiency state and their correction, especially in those people at higher risk.
27306356 Echocardiography in the Assessment of Patients with Rheumatologic Diseases. 2016 Aug Cardiovascular disease is an important extra-articular manifestation of rheumatologic diseases leading to considerable mortality and morbidity. Echocardiography emerges as a useful non-invasive technique for the screening and evaluation of cardiac involvement in these patients. With the technological advancement in echocardiographic techniques, we have gained a greater appreciation of the prevalence and nature of the cardiac involvement in these patients, as detection of subclinical disease is increasingly feasible. This review discusses cardiac involvement in patients with rheumatoid arthritis, systemic lupus erythematosus, anti-phospholipid antibody syndrome, systemic sclerosis and ankylosing spondylitis, and the role of different echocardiographic modalities in their evaluation.
27249518 Epigenetic biomarkers in rheumatology - the future? 2016 Epigenetic changes are stable modifications of DNA or histones that profoundly alter gene expression. They can be changed by environmental influences and can then be passed on to daughter cells or via the germ line to offspring. A variety of changes in epigenetic marks and in the expression of noncoding RNA has been found in cancer as well as in chronic inflammatory diseases. Interestingly, in both diseases similar mechanisms and pathways are affected albeit often to a different extent. DNA methylation is often lost in repetitive sequences, while in promoter regions hypo- as well as hypermethylation is found. Changes in microRNA levels typically affect microRNAs that are changed by an inflammatory environment, but disease specific changes have also been found in the blood and various cell types of patients with rheumatoid arthritis, systemic lupus erythematosus and other rheumatic diseases. Therefore, changes in the expression of microRNA in particular, but also demethylated gene loci, have been proposed as potential biomarkers in chronic inflammatory diseases and in cancer. Potentially, these changes could be used for early diagnosis and also to predict treatment response. Unfortunately most studies in rheumatology up to now were not designed to validate these epigenetic changes as biomarkers. Since the cancer field is much more advanced in the usage of biomarkers for disease subclassifications and subsequent therapeutic decisions, it is worthwhile to take a closer look at the biomarkers, methods and procedures used in oncology and to see which of these could also be applied to predicting disease severity and therapeutic response in rheumatic diseases. This article will highlight common epigenetic pathways activated in cancer and various rheumatic diseases and summarise epigenetic changes that have the potential to become biomarkers in rheumatic diseases.
26988082 Imaging of connective tissue diseases of the head and neck. 2016 Jun We review the imaging appearance of connective tissue diseases of the head and neck. Bilateral sialadenitis and dacryoadenitis are seen in Sjögren's syndrome; ankylosis of the temporo-mandibular joint with sclerosis of the crico-arytenoid joint are reported in rheumatoid arthritis and lupus panniculitis with atypical infection are reported in patients with systemic lupus erythematosus. Relapsing polychondritis shows subglottic stenosis, prominent ear and saddle nose; progressive systemic sclerosis shows osteolysis of the mandible, fibrosis of the masseter muscle with calcinosis of the subcutaneous tissue and dermatomyositis/polymyositis shows condylar erosions and autoimmune thyroiditis. Vascular thrombosis is reported in antiphospholipid antibodies syndrome; cervical lymphadenopathy is seen in adult-onset Still's disease, and neuropathy with thyroiditis reported in mixed connective tissue disorder. Imaging is important to detect associated malignancy with connective tissue disorders. Correlation of the imaging findings with demographic data and clinical findings are important for the diagnosis of connective tissue disorders.
26942206 Human Macrophages Utilize the Podosome Formin FMNL1 for Adhesion and Migration. 2015 Mar Macrophages play a crucial role in detecting, regulating, and resolving immune crises, requiring migration through complex extracellular matrices. Unwarranted macrophage inflammatory activity potentiates kidney disease, rheumatoid arthritis, and transplant rejection. Proper remodeling of the actin cytoskeleton, especially at adhesion structures, is essential to the translocation of macrophages. Macrophages form actin-rich adhesions termed "podosomes", giving them the capacity to make contacts with the substratum for traction through interstitial tissues. Macrophages express multiple formins, including FMNL1, Dia1, and Fhod1, with potential to impact actin remodeling involved in migration. Formins are a family of proteins that are best known for modifying the actin cytoskeleton via nucleation, elongation, bundling, and/or severing actin filaments. In this study we demonstrate that the formin FMNL1 is a key regulator of podosomes and is required for normal macrophage migration. Additionally, this is the first study to demonstrate defects in primary human cell migration resulting from specific formin silencing. Pharmacologic inhibition of all formin activity results in a significant decrease in podosome formation and normal macrophage migration. Furthermore, targeted suppression of FMNL1 results in decreases in macrophage migration similar to inhibition of all expressed macrophage formins. These novel findings suggest FMNL1 as a possible chemotherapeutic target to hinder macrophage migration, which could offer an innovative method for limiting unnecessary macrophage-mediated inflammation. We hypothesize that formins are required in podosome actin dynamics to support macrophage migration.
26809011 Treat-to-target in systemic lupus erythematosus: are we there yet? 2016 The treat-to-target (T2T) strategy has proven benefits in several chronic medical illnesses including rheumatoid arthritis. Whether the T2T principle can be applied to SLE has become a recent topic of discussion. A European panel of rheumatologists agrees that treatment of SLE should target at multiple goals that include control of disease activity, prevention of disease flares, minimization of disease or treatment related comorbidity, and improvement of quality of life. Therapy of SLE should aim at remission or when remission cannot be achieved, the lowest possible disease activity that is assessed by a validated lupus activity index and/or organ-specific markers. However, owing to the clinical heterogeneity of SLE, there is still no consensus on the definition of remission or low disease activity state in individual organ-systems. In real life, agents readily available for therapy switching in SLE are limited. Moreover, no disease activity index is universally agreed upon for disease monitoring to make therapeutic decisions. Currently, clinical parameters for the assessment and monitoring of lupus renal disease appear to be more objective and evidence-based. A therapeutic target in terms of proteinuria and/or other renal parameters should be tested in randomized controlled trials for the proof of the T2T concept in SLE.
26768758 The crossroads of autoimmunity and immunodeficiency: Lessons from polygenic traits and mon 2016 Jan Autoimmune and immunodeficiency diseases are outcomes of a dysfunctional immune system and represent 2 sides of the same coin. Multiple single-gene defects have been identified, resulting in rare diseases with features of both autoimmunity and immunodeficiency. On the other hand, more common autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, show a polygenic inheritance pattern. Not surprisingly, the genes implicated in single-gene disorders have also been shown to be linked to polygenic disorders. In this review article, we discuss the contribution of various immune system genes to common polygenic autoimmune disorders, as well as the pathophysiologic pathways and clinical features of monogenic defects that result in autoimmune disease. We also explore the hypotheses underlying the development of autoimmune disease and the overlap between immunodeficiency and autoimmunity.
26226330 Pharmacotherapy in the ageing patient: The impact of age per se (A review). 2015 Nov A literature search was carried out to review the influence of 'ageing' on pharmacotherapeutic decision-making, specifically how 'age' is defined and considered in the utilisation of medication. Embase, Medline, International Pharmaceutical Abstracts, and Google scholar were canvassed in a three-tiered search according to pre-established inclusion criteria. In tier 1, a total of 22 studies were identified highlighting the underutilisation of medication in elderly patients, with a particular focus on warfarin. Four studies highlighted an age-bias in medication-prescribing for elderly patients, specifically in relation to medicines for rheumatoid arthritis, angina, and hypertension. Tier 2 identified diverse definitions for 'elderly', including biological age, chronological age, physiological age, as well as various descriptions of 'elderly' in clinical trials and guidelines. Finally, medication optimisation tools were identified through the third tier, emphasising the use of chronological age to describe the 'elderly'. Old age influences pharmacotherapeutic decision-making at various levels, however, what complicates the situation is the absence of a comprehensive definition of 'elderly'. Clinical recommendations need to be based more on objective factors known to affect medication effectiveness and safety.
25915571 Complicating autoimmune diseases in myasthenia gravis: a review. 2015 Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis.
25892741 Applications of Multiple Reaction Monitoring to Clinical Glycomics. 2015 Mar 1 Multiple reaction monitoring or MRM is widely acknowledged for its accuracy of quantitation. The applications have mostly been in the analysis of small molecules and proteins, but its utility is expanding. Protein glycosylation was recently identified as a new paradigm in biomarker discovery for health and disease. A number of recent studies have now identified differential glycosylation patterns associated with health and disease states, including aging, pregnancy, rheumatoid arthritis and different types of cancer. While the use of MRM in clinical glycomics is still in its infancy, it can likely play a role in the quantitation of protein glycosylation in the clinical setting. Here, we aim to review the current advances in the nascent application of MRM in the field of glycomics.
25861493 JC Virus PCR Detection Is Not Infallible: A Fulminant Case of Progressive Multifocal Leuko 2015 We describe a case with a false-negative PCR-based analysis for JC virus in cerebrospinal fluid (CSF) in a patient with clinical and radiological findings suggestive of progressive multifocal leukoencephalopathy (PML) who was on chronic immunosuppressive therapy for rheumatoid arthritis. Our patient developed rapidly progressive global decline with clinical and radiographic findings suggestive of PML, but JC virus PCR in CSF was negative. The patient passed away 3 months from the onset of her neurological symptoms. Autopsy confirmed the diagnosis of PML with presence of JC-polyoma virus by immunohistochemical staining. This case highlights the potential of false-negative JC virus PCR in CSF when radiographic and clinical features are suggestive of "possible PML." We review the plausible causes of potential false-negative CSF results and suggest that when the clinical presentation is suspicious for PML repeat CSF analysis utilizing ultrasensitive PCR assay and subsequent brain biopsy should be considered if CSF remains negative. Additionally, appropriate exclusion of other neurologic conditions is essential.
25842185 Exosomes as nanocarriers for immunotherapy of cancer and inflammatory diseases. 2015 Sep Cell secreted exosomes (30-100nm vesicles) play a major role in intercellular communication due to their ability to transfer proteins and nucleic acids from one cell to another. Depending on the originating cell type and the cargo, exosomes can have immunosuppressive or immunostimulatory effects, which have potential application as immunotherapies for cancer and autoimmune diseases. Cellular components shed from tumor cells or antigen presenting cells (APCs), such as dendritic cells, macrophages and B cells, have been shown to be efficiently packaged in exosomes. In this review, we focus on the application of exosomes as nanocarriers and immunological agents for cancer and autoimmune immunotherapy. APC-derived exosomes demonstrate effective therapeutic efficacy for the treatment of cancer and experimental autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. In addition to their intrinsic immunomodulating activity, exosomes have many advantages over conventional nanocarriers for drug and gene delivery.
25693496 [Pulmonary manifestations of connective tissue diseases]. 2015 Mar Systemic autoimmune diseases are responsible for about 25% of all deaths due to interstitial lung disease; therefore, an early identification of patients with pulmonary manifestation changes the management. Detection, differential diagnostic classification and staging of the pneumological pattern of findings are largely based on high-resolution computed tomography (HR-CT). The main differential diagnostic challenges are interstitial manifestations which present with radiological-histopathological phenotypes of interstitial pneumonia. The most common form of interstitial pulmonary reaction form of connective tissue diseases is the nonspecific interstitial pneumonia (NSIP) pattern. In rheumatoid arthritis, a usual interstitial pneumonia (UIP) pattern is dominant. Uncharacteristic reactions of airways and pleura can be the leading symptom or present as accompanying findings. A serious complication is pulmonary hypertension. Drug-induced lung lesions can present with similar HR-CT morphology as connective tissue diseases and can only be differentiated in the temporal and clinical context.