Browse

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

ID PMID Title PublicationDate abstract
21185665 Bilateral patellar tendon ruptures without predisposing systemic disease or steroid use: a 2012 Jan Simultaneous bilateral patellar tendon rupture occurs rarely and is even rarer in patients without systemic disease or predisposing conditions. We present a case of bilateral, midsubstance patellar tendon ruptures along with a partial anterior cruciate ligament tear from a fall from a standing height in an otherwise healthy adult without any predisposing conditions. Most patients that sustain a tendon rupture have risk factors for tendonopathy including chronic renal disease, systemic lupus erythematosus, rheumatoid arthritis, or exposure to medications (such as corticosteroids or fluoroquinolones). Currently, there are approximately 50 reported cases of bilateral patellar tendon rupture in the scientific literature; however, only a small minority occurred in patients without any predisposing factors. Most of the reports of a bilateral tendon rupture without systemic disease occurred in the inferior pole of the tendon, with only a few of these occurring in the midsubstance. Because of the rarity of this event in a patient without systemic disease, this condition is often misdiagnosed. Emergency physicians should maintain a high degree of suspicion in those patients with concerning clinical and/or radiographic findings.
23147903 Coagulation and the fibrin network in rheumatic disease: a role beyond haemostasis. 2012 Dec Activation of the immune system has been increasingly recognised to be associated with procoagulatory status in patients with inflammatory rheumatic disease. Changes in endothelial cell and platelet activation, blood flow, expression and activity of different coagulation factors, and impaired fibrinolysis serve as pathophysiological basis for enhanced risk of venous thromboembolism in inflammatory rheumatic diseases, such as rheumatoid arthritis (RA), connective tissue diseases and vasculitides. Recent studies identifying mechanisms for a functional role of coagulation factors beyond haemostasis have provided examples of interesting links between the coagulation system and innate immune activation. Furthermore, citrullinated fibrinogen is an important and early autoantigen in patients with RA carrying the HLA-DRβ1 shared epitope allele, which demonstrates an adaptive immune response to a coagulation factor in an inflammatory rheumatic disease. Additional studies have provided strong evidence that a multitude of different components of the haemostatic system (such as thrombin, fibrinogen, coagulation factor XIII and factors of the fibrinolytic system) are relevant mediators of inflammatory processes as well as of inflammatory control. Understanding the interactions between coagulation and the immune system in inflammatory rheumatic diseases will not only improve our knowledge of disease mechanisms, but could also permit the development of innovative therapeutic interventions.
22660185 Bone cell interactions through Eph/ephrin: bone modeling, remodeling and associated diseas 2012 Mar Bones cannot properly form or be maintained without cell-cell interactions through ephrin ligands and Eph receptors. Cell culture analysis and evaluation of genetic mouse models and human diseases reveal various ephrins and Eph functions in the skeletal system. Migration, attachment and spreading of mesenchymal stem cells are regulated by ephrinB ligands and EphB receptors. ephrinB1 loss-of-function is associated with craniofrontonasal syndrome (CFNS) in humans and mice. In bone remodeling, ephrinB2 is postulated to act as a "coupling stimulator." In that case, bidirectional signaling between osteoclastic ephrinB2 and osteoblastic EphB4 suppresses osteoclastic bone resorption and enhances osteoblastic bone formation, facilitating the transition between these two states. Parathyroid hormone (PTH) induces ephrinB2 in osteoblasts and enhances osteoblastic bone formation. In contrast to ephrinB2, ephrinA2 acts as a "coupling inhibitor," since ephrinA2 reverse signaling into osteoclasts enhances osteoclastogenesis and EphA2 forward signaling into osteoblasts suppresses osteoblastic bone formation and mineralization. Furthermore, ephrins and Ephs likely modulate pathological conditions such as osteoarthritis, rheumatoid arthritis, multiple myeloma and osteosarcoma. This review focuses on ephrin/Eph-mediated cell-cell interactions in bone biology.
27625807 Pharmacogenomics and its importance in pediatric medicine. 2012 Jun Individual variation in drug response and adverse drug reactions (ADRs) are a serious problem in medicine. This individual variation in drug response could be due to multiple factors but there is strong evidence that genetic factors play a significant role in drug response variability and toxicity. Although substantial studies that link genetic variants to inter-individual difference in drug response in adults have been reported, such studies are comparatively rare in pediatric medicine. The ultimate goal of medical research is to improve human health in every disease and every patient. Many diseases such as asthma, autism, epilepsy, juvenile rheumatoid arthritis and attention-deficit hyperactivity disorder develop during childhood. Human development is a rapidly changing process. In children, there are differences in absorption, distribution, excretion and metabolizing capabilities of a drug compared with adults. Therefore, many pharmacological and toxicological actions of drugs in children are not predictable from adult experience. It is also possible that children may experience a different range of ADRs that may have long-term implications for their development. Therefore, an improved understanding of the drug transformation pathways for all age groups is necessary. Such studies could provide insight into the susceptibility of a child to ADRs. The availability of the complete sequence of human genome and the biochip technology may help in identifying the polymorphic variations in drug related genes. In this regard, pharmacogenetic and pharmacogenomic studies may play an important role in providing markers of increased risk or susceptibility. Based on this genetic information, children at risk can be identified before therapy is initiated and pediatric ADRs may be minimized. In this short article, an attempt has been made to emphasize the importance of pharmacogenomics in pediatrics.
22342162 Central nervous system inflammation in disease related conditions: mechanistic prospects. 2012 Mar 29 Inflammation is part of the innate immune response following insults to the body. This inflammatory reaction can spread throughout the systemic circulation and also into the central nervous system (CNS). CNS involvement has been demonstrated following acute peripheral insults including sepsis, surgery, burns and organ injury. It has also been observed in chronic conditions including obesity, diabetes and rheumatoid arthritis. Inflammation within the CNS is part of the pathogenesis of neurodegenerative diseases, in particular Alzheimer's disease, multiple sclerosis and Parkinson's disease. These diseases are prone to exacerbation as a result of increased inflammation within the CNS following peripheral insult. The effect of inflammation within the CNS can also be modulated by other factors including age and also oestrogen, although how pro-inflammatory cytokines within the CNS cause clinical changes remains to be elucidated. The mechanism underlying the passage of inflammation from the periphery into the CNS also remains unclear. Evidence has led to the suggestion of two main pathways: blood brain barrier (BBB) dependent and BBB independent. This uncertainty has led to an increasing body of work exploring the processes involved in both the passage of inflammation into, and the effect of cytokines on, the CNS.
22133829 [Bone and calcium update; bone research update. Osteoclastogenesis and osteoimmunology]. 2011 Dec Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption. This restructuring process called "bone remodeling" is important not only for maintaining bone mass and strength, but also for mineral homeostasis. Excessive osteoclast activity leads to pathological bone resorption, as seen in a variety of local or generalized osteopenic conditions such as rheumatoid arthritis, cancer bone metastasis and osteoporosis. The immune and skeletal systems share various molecules including cytokines, signaling molecules, transcription factors and membrane receptors. The scope of osteoimmunology has been extended to encompass a wide range of molecular and cellular interactions, the elucidation of which will provide a scientific basis for future therapeutic approaches to diseases related to the immune and skeletal systems.
21731554 Microalgae as sources of carotenoids. 2011 Marine microalgae constitute a natural source of a variety of drugs for pharmaceutical, food and cosmetic applications-which encompass carotenoids, among others. A growing body of experimental evidence has confirmed that these compounds can play important roles in prevention (and even treatment) of human diseases and health conditions, e.g., cancer, cardiovascular problems, atherosclerosis, rheumatoid arthritis, muscular dystrophy, cataracts and some neurological disorders. The underlying features that may account for such favorable biological activities are their intrinsic antioxidant, anti-inflammatory and antitumoral features. In this invited review, the most important issues regarding synthesis of carotenoids by microalgae are described and discussed-from both physiological and processing points of view. Current gaps of knowledge, as well as technological opportunities in the near future relating to this growing field of interest, are also put forward in a critical manner.
21419275 Vitamin D deficiency and connective tissue disease. 2011 Recently, the evidence linking vitamin D status as a potential environmental factor affecting autoimmune disease prevalence continues to accumulate. Beyond that the traditional known metabolic activities, vitamin D has been shown to modulate the immune system and has anti-inflammatory properties. The immune-regulatory role of vitamin D affects both the innate and adaptive immune responses contributing to the immune-tolerance of self-structures. Vitamin D deficiency skews the immunologic response towards loss of tolerance. Serum levels of vitamin D have been found to be significantly lower in several autoimmune or immune-mediated diseases than in the healthy population. Experimental animal models and clinical studies show that 1,25-dihydroxyvitamin D3 or vitamin D receptor (VDR) agonists can either prevent or suppress symptoms of type 1 diabetes, experimental autoimmune encephalomyelitis, rheumatoid arthritis, systemic lupus erthyematosus and inflammatory bowel disease. The heading aims at reviewing the complex immune-regulatory role of vitamin D from the cellular and humoral level through animal models of autoimmune rheumatic diseases and representing the known contribution of vitamin D in the pathogenesis of connective tissue diseases. Increased vitamin D intakes might reduce the incidence and severity of autoimmune disorders besides reducing the rate of osteoporotic bone fracture.
21395511 Role of activin A in the induction of Foxp3+ and Foxp3- CD4+ regulatory T cells. 2011 Regulatory T cells (Tregs) play a crucial role in the maintenance of immune homeostasis. The two best studied types of CD4(+) regulatory T cells are the Foxp3(+) Tregs and the T regulatory type 1 (Tr1) cells. CD4(+) regulatory T cells play a protective role in autoimmune disease. On the other hand, they also may have pathogenic properties in infectious diseases and carcinogenesis. Because of their potential for the therapy of various human diseases, factors responsible for expanding regulatory T cells are of interest. One of these factors, the TGFbeta family member activin A, is expressed in different inflammatory conditions, such as inflammatory bowel disease, rheumatoid arthritis, and asthma. Although activin A might have pro- and anti-inflammatory properties depending on the context of expression, this review focuses on the role of activin A for the expansion of the CD4(+) regulatory T-cell pool.
21312334 Azamacrocyclic metal complexes as CXCR4 antagonists. 2011 May 2 The chemokine receptor CXCR4 is a member of the seven transmembrane GPCR family, which is implicated in multiple diseases, including HIV infection, cancers, and rheumatoid arthritis. Low-molecular-weight nonpeptidic compounds, including AMD3100 and various pyridyl macrocyclic zinc(II) complexes, have been identified as selective antagonists of CXCR4. In the present study, structure-activity relationship studies were performed by combining the common structural features of alkylamino and pyridiyl macrocyclic antagonists. Several new zinc(II) or copper(II) complexes demonstrated potent anti-HIV activity, strong CXCR4-binding activity, and significant inhibitory activity against Ca(2+) mobilization induced by CXCL12 stimulation. These results may prove useful in the design of novel CXCR4 antagonists, and the compounds described could potentially be developed as therapeutics against CXCR4-relevant diseases or chemical probes to study the biological activity of CXCR4.
21283147 Pain, catastrophizing, and depression in the rheumatic diseases. 2011 Apr Persistent and disabling pain is the hallmark of osteoarthritis, rheumatoid arthritis, fibromyalgia, and various other rheumatologic conditions. However, disease severity (as measured by 'objective' indices such as those that employ radiography or serology) is only marginally related to patients' reports of pain severity, and pain-related presentation can differ widely between individuals with ostensibly similar conditions (for example, grade 4 osteoarthritis of the knee). Increasing evidence in support of the biopsychosocial model of pain suggests that cognitive and emotional processes are crucial contributors to inter-individual differences in the perception and impact of pain. This Review describes the growing body of literature relating depression and catastrophizing to the experience of pain and pain-related sequelae across a number of rheumatic diseases. Depression and catastrophizing are consistently associated with the reported severity of pain, sensitivity to pain, physical disability, poor treatment outcomes, and inflammatory disease activity, and potentially with early mortality. A variety of pathways, from cognitive to behavioral to neurophysiological, seem to mediate these deleterious effects. Collectively, depression and catastrophizing are critically important variables in understanding the experience of pain in patients with rheumatologic disorders. Pain, depression, and catastrophizing might all be uniquely important therapeutic targets in the multimodal management of a range of such conditions.
21269234 The impact of biologic response modifiers on hepatitis B virus infection. 2011 Apr INTRODUCTION: The biologic response modifiers are a diverse group of medications that have emerged over the last decade. They target pro-inflammatory cytokines or cell surface molecules that drive illnesses such as rheumatoid arthritis. Despite the greater control afforded they have also ushered in a new spectrum of side effects. As the same immunologic machinery that helps control infections such as HBV contributes to the pathogenesis of rheumatologic diseases, persistence or reactivation of the virus remains an evolving concern. AREAS COVERED: A systemic literature review was performed using the PubMed and Medline databases (1996 to January 2010) searching for the index term 'Hepatitis B' combined with the terms 'tumor necrosis factor', 'B cell', 'rituximab', 'IL-1', 'anakinra', 'IL-6', 'tocilizumab', 'CTLA-4', and 'abatacept'. All relevant articles in English were reviewed and secondary references of interest were also retrieved. This paper addresses the role of the various cytokines and cluster of differentiation molecules in controlling HBVinfection and the currently known effect that the biologic response modifiers have on viral control by the host immune response. EXPERT OPINION: The risk of HBV reactivation is greatest in HBsAg positive patients. These patients should start antiviral therapy one week before receiving a biologic response modifier. The risk of HBV reactivation in HBsAg negative patients appears very low but when HBsAb titers are low use of rituximab or TNF-α antagonists may increase the risk of reactivation.
21247392 Mean platelet volume: a link between thrombosis and inflammation? 2011 Platelet activation is a link in the pathophysiology of diseases prone to thrombosis and inflammation. Numerous platelet markers, including mean platelet volume (MPV), have been investigated in connection with both thrombosis and inflammation. This review considers MPV as a prognostic and therapeutic marker as well as the factors influencing its measurement. Established cardiovascular risk factors, such as smoking, hypertension, dyslipidemia, and diabetes, can influence MPV, depending on confounding factors. Low-grade inflammation is one such factor. Evidence, particularly derived from prospective studies and a meta-analysis, suggest a correlation between an increase in MPV and the risk of thrombosis. High MPV associates with a variety of established risk factors, cardio- and cerebrovascular disorders, and low-grade inflammatory conditions prone to arterial and venous thromboses. High-grade inflammatory diseases, such as active rheumatoid arthritis or attacks of familial Mediterranean fever, present with low levels of MPV, which reverse in the course of anti-inflammatory therapy. Lifestyle modification, antihypertensive, lipid lowering and diet therapies can also affect MPV values, but these effects need to be investigated in large prospective studies with thrombotic endpoints.
20672910 The dangerous liaison between iNKT cells and dendritic cells: does it prevent or promote a 2011 Feb Invariant natural killer T (iNKT) cells represent an important regulatory T-cell subset that perceives signals of danger and/or cellular distress and modulate the adaptive immune response accordingly. In the presence of pathogens, iNKT cells acquire an adjuvant function that is fundamental to boost anti-microbial and anti-tumor immunity. At the same time, iNKT cells can play a negative regulatory function to maintain peripheral T-cell tolerance toward self-antigens and to prevent autoimmune disease. Both these effects of iNKT cells involve the modulation of the activity of dendritic cells (DCs) through cell-cell interaction. Indeed, iNKT cells can either boost Th1 immunity by enhancing maturation of pro-inflammatory DCs or promote immune tolerance through the maturation of tolerogenic DCs. This dual action of iNKT cells opens questions on the modalities by which a single-cell subset can exert opposite effects on DCs and may even put in question the overall immunosuppressive properties of iNKT cells. This review presents the large body of evidence that shows the ability of iNKT cells to negatively regulate autoimmunity and to prevent autoimmune diseases including multiple sclerosis, type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus. In addition, an update is provided on the mechanisms of iNKT-DCs interactions and how this can result in inflammatory or tolerogenic responses.
21548849 MEK inhibitors: a patent review 2008 - 2010. 2011 Jul INTRODUCTION: MAPK/extracellular signal-regulated kinase (MEK) inhibitors target the Ras/Raf/MEK/ERK signaling pathway, which is important in cell growth, differentiation and development. The pathway has been implicated in the progression of a variety of diseases, in particular cancer, as well as in immune and inflammatory diseases such as rheumatoid arthritis, organ transplant rejection, septic shock, asthma and viral infection. AREAS COVERED: A comprehensive review of the patent literature (2008 - 2010) covering MEK inhibitors and combinations thereof is provided in this paper. EXPERT OPINION: The first MEK inhibitor was described in the literature in 1995, and several companies are still active in the research and development of MEK inhibitors for various disease states. The emerging role of MEK inhibitors in disease has prompted further investigations of this important target. The combination of MEK inhibitors with other agents/therapies in the treatment of diseases, particularly cancer, is a key development in the field.
21530402 Interferon-β exacerbates Th17-mediated inflammatory disease. 2011 Jun Interferon (IFN)-β is the treatment most often prescribed for relapsing-remitting multiple sclerosis (RRMS). 30-50% of MS patients, however, do not respond to IFN-β. In some cases, IFN-β exacerbates MS, and it consistently worsens neuromyelitis optica (NMO). To eliminate unnecessary treatment for patients who are non-responsive to IFN-β, and to avoid possible harm, researchers are identifying biomarkers that predict treatment outcome before treatment is initiated. These biomarkers reveal insights into the mechanisms of disease. Recent discoveries on human samples from patients with RRMS, NMO, psoriasis, rheumatoid arthritis, systemic lupus erythematosus and ulcerative colitis, indicate that IFN-β is ineffective and might worsen clinical status in diverse diseases when a Th17 immune response is prominent.
21482522 [Identification of a novel lymphotoxin-alpha (LTA) gene associated with ankylosing spondyl 2011 Apr Lymphotoxin-alpha (LTA) gene has been reported to have a genetic association with systemic lupus erythematosus (SLE), psoriasis, and rheumatoid arthritis. However, the association of LTA with ankylosing spondylitis (AS) has not reported. By case-control study, we carried out the high density limited genome scanning to the HLA class III region about 58 kb in Ningxia population (case 300 and control 385). In this study, 33 SNPs in LTA were genotyped in Ningxia population. We analyzed these SNPs and the haplotypes covering LTA. Only the distribution of TCC haplotype which contains mutation allele of LTA rs909253 was statistically significant(P=0.0005). The C allele frequency of the LTA rs909253 T/C polymorphism was higher in AS cases than that in the controls (28.5% versus 19.7%, P=2×10-4) in Ningxia population. The results suggest that there is a relevance between LTA and the susceptibility of AS, and we identified that the LTA polymorphism may be associated with AS in Ningxia population.
21245642 Peripheral T-cell lymphoma that developed during the follow-up of IgG4-related disease. 2011 IgG4-related disease is a recently recognized fibroinflammatory disorder characterized by extensive IgG4-positive plasma cell and lymphocyte infiltration of various organs. The pancreatic manifestation of IgG4-related disease is called autoimmune pancreatitis (AIP), in which autoimmune mechanisms are likely involved. On the other hand, some autoimmune and chronic inflammatory disorders, such as Sjögren's syndrome and rheumatoid arthritis, are associated with increased risks of non-Hodgkin lymphoma (NHL). There have been a few reports of cases with IgG4-related disease that had subsequently developed NHL, however, all of them suffered from B-cell lymphoma. We describe the first case of NHL, compatible with a subtype of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), which arose in IgG4-related sclerosing cholangitis. As patients with IgG4-related disease may be at an increased risk of developing NHL, such presentation during the follow-up of IgG4-related disease should be carefully scrutinized to exclude NHL.
23319323 Voltage-dependent anion channels (VDACs, porin) expressed in the plasma membrane regulate 2013 Jan Fewer molecules have been identified on human than murine osteoclasts, the former differing from murine osteoclasts in many ways. We show that voltage-dependent anion channels (VDACs, porin) are expressed in the plasma membrane of human osteoclasts. A search for novel proteins expressed in the plasma membrane of human osteoclasts identified VDAC. Anti-VDAC antibodies inhibited human osteoclastogenesis in vitro. VDAC expression was detected in membranes by immunoelectron microscopy and immunocytochemical double staining. The VDAC protein functions as a Cl(-) channel. VDACs regulate bone resorption, which show using Osteologicâ„¢ plates. The epitope of the antibody lay within a 10-amino acid sequence in the VDAC. The findings suggest that the VDAC is, at least partly, a novel Cl(-) channel regulating the differentiation and function of human osteoclasts. VDACs may play a crucial role in acidifying the resorption lacunae between osteoclasts and bone. Inhibitors of VDACs could be used to treat diseases involving increased resorption, such as osteoporosis, rheumatoid arthritis, and Paget's disease.
23267667 Metabolite profile analysis of aconitine in rabbit stomach after oral administration by li 2013 Jul 1. Aconitine (AC), an active and highly toxic constituent extracted from aconitum plants, is well known for its excellent effects against rheumatism and rheumatoid arthritis. The metabolism of AC in liver and intestine has been previously reported. However, little is known about the metabolism of AC in stomach. In this study, the metabolite profiling of AC in stomachs of rabbit and rat was performed by liquid chromatography/electrospray ionization/multiple-stage tandem mass spectrometry (LC/ESI/MS(n)), for the first time. 2. The samples were purified by liquid-liquid extraction, separated using an Agilent extended C18 column following a linear gradient elution and then detected by ESI/MS(n) in positive ion mode. Metabolites were identified by comparing their protonated molecules, fragmentation patterns and chromatographic behaviors with those of standard compounds and data from authorized literature works. 3. In conclusion, 14 metabolites were identified in animal stomach after oral administration of AC. The presentation of a large amount of metabolites of AC in stomach suggested that, for aconitum alkaloids, the stomach might play an important role in their metabolism.