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ID PMID Title PublicationDate abstract
21036646 Diagnostic strategy for patients with hypogammaglobulinemia in rheumatology. 2011 May The discovery of hypogammaglobulinemia, which is defined as a plasmatic level of immunoglobulin (Ig) under 5 g/L is rare in clinical practice. However, the management of immunodepressed patients in rheumatology, sometimes due to the use of immunosuppressive treatments such as anti-CD20 in chronic inflammatory rheumatisms, increases the risk of being confronted to this situation. The discovery of hypogammaglobulinemia in clinical practice, sometimes by chance, must never be neglected and requires a rigorous diagnosis approach. First of all, in adults, secondary causes, in particular lymphoid hemopathies or drug-related causes (immunosuppressors, antiepileptics) must be eliminated. A renal (nephrotic syndrome) or digestive (protein-losing enteropathy) leakage of Ig is also possible. More rarely, it is due to an authentic primary immunodeficiency (PID) discovered in adulthood: common variable immunodeficiency (CVID) which is the most frequent form of PID, affects young adults between 20 and 30 years and can sometimes trigger joint symptoms similar to those in rheumatoid arthritis; or Good syndrome, which associates hypogammaglobulinemia, thymoma and recurrent infections around the age of 40 years. In most cases, after confirming hypogammaglobulinemia on a second test, biological examinations and thoracic-abdominal-pelvic CT scan will guide the diagnosis, after which the opinion of a specialist can be sought depending on the findings of the above examinations. At the end of this review, we provide a decision tree to guide the clinician confronted to an adult-onset hypogammaglobulinemia.
20803050 Reimbursement of pharmaceuticals: reference pricing versus health technology assessment. 2011 Jun Reference pricing and health technology assessment are policies commonly applied in order to obtain more value for money from pharmaceuticals. This study focussed on decisions about the initial price and reimbursement status of innovative drugs and discussed the consequences for market access and cost. Four countries were studied: Germany, The Netherlands, Sweden and the United Kingdom. These countries have operated one, or both, of the two policies at certain points in time, sometimes in parallel. Drugs in four groups were considered: cholesterol-lowering agents, insulin analogues, biologic drugs for rheumatoid arthritis and "atypical" drugs for schizophrenia. Compared with HTA, reference pricing is a relatively blunt instrument for obtaining value for money from pharmaceuticals. Thus, its role in making reimbursement decisions should be limited to drugs which are therapeutically equivalent. HTA is a superior strategy for obtaining value for money because it addresses not only price but also the appropriate indications for the use of the drug and the relation between additional value and additional costs. However, given the relatively higher costs of conducting HTAs, the most efficient approach might be a combination of both policies.
24426249 Antioxidant status and oxidative stress in the circulation of younger and elderly human su 2013 Oct Extensive research has demonstrated the protective properties of antioxidants, which scavenge reactive oxygen species and their precursors, as well as up-regulate enzymes involved in the repair of cellular damage. Several case-control studies have showed higher blood levels of antioxidants and decreased oxidative stress in younger individuals when compared with older ones. Cell damage caused by free radicals appears to be a major contributor in aging and degenerative diseases of aging such as cancer, cardiovascular disease, cataracts, compromised immune system, rheumatoid arthritis and brain dysfunction. The objective of this study was to determine the variation of Circulating levels of selected antioxidants (enzymic and non enzymic) and oxidative stress marker in younger and older humans. The results showed that a majority of the younger age group participants showed a significant increase in enzymic and nonenzymic antioxidant status and a decrease in oxidative stress when compared with the older age group.
27231402 Ultrasensitive impedimetric lectin based biosensor for glycoproteins containing sialic aci 2013 Jan We report on an ultrasensitive label-free lectin-based impedimetric biosensor for the determination of the sialylated glycoproteins fetuin and asialofetuin. A sialic acid binding agglutinin from Sambucus nigra I was covalently immobilised on a mixed self-assembled monolayer (SAM) consisting of 11-mercaptoundecanoic acid and 6-mercaptohexanol. Poly(vinyl alcohol) was used as a blocking agent. The sensor layer was characterised by atomic force microscopy, electrochemical impedance spectroscopy and X-ray photoelectron spectroscopy. The biosensor exhibits a linear range that spans 7 orders of magnitude for both glycoproteins, with a detection limit as low as 0.33 fM for fetuin and 0.54 fM for asialofetuin. We also show, by making control experiments with oxidised asialofetuin, that the biosensor is capable of quantitatively detecting changes in the fraction of sialic acid on glycoproteins. We conclude that this work lays a solid foundation for future applications of such a biosensor in terms of the diagnosis of diseases such as chronic inflammatory rheumatoid arthritis, genetic disorders and cancer, all of which are associated with aberrant glycosylation of protein biomarkers.
24516733 The role of the Epstein-Barr virus in the pathogenesis of some autoimmune disorders - Simi 2011 Dec After a brief summary on the properties of the Epstein-Barr virus (EBV), the course and latency stages of the infection, the characteristics of infectious mononucleosis (IM), and other disorders caused by this virus, as well as the course of the serological responses to EBV, the current paper focuses on the role of EBV in two autoimmune disorders: multiple sclerosis (MS), and systemic lupus erythematosus (SLE). Diverse evidence suggests that infection by EBV during late childhood or young adulthood may have a role in the pathogenesis of MS. These include the similarity between the geographical distribution of IMand MS, the high risk of contracting MS by individuals who have recovered from IM, the elevation of the titers of IgG antibodies against EBV nuclear antigens occurring years before the initial manifestations of MS, and the extremely rare occurrence of MS in individuals seronegative for EBV. However, the data on the mechanism underlying the relationship between EBV and MS are controversial. Moreover, many observations indicate that EBV contributes also to the pathomechanism of SLE. However, this contribution differs from the relationship between EBV and MS, as shown by the lack of any increase in the risk of SLE after IM. In SLE, EBV serology is quantitatively and qualitatively different from the normal response - that is, EBV viral load is higher and a strong cross-reaction can be detected between certain EBV antigens and autoantigens of pathological importance. These observations, along with the findings pointing to a possible role of EBV in rheumatoid arthritis and myasthenia gravis indicate that infection by EBV may be one of the environmental factors, which can facilitate the development of some autoimmune disorders in genetically susceptible individuals.
21942253 What is the potential for inhaled p38 inhibitors in the treatment of chronic obstructive p 2011 Oct p38 has been an intensely studied therapeutic target in the pharmaceutical industry. With more than 20 compounds entering human trials, none have progressed beyond Phase II to the best of our knowledge. The transient efficacy seen in many of the Phase II trials has raised some concerns for the future potential of this target, particularly in rheumatoid arthritis. With this caveat, there is good evidence for p38 inhibition to be efficacious in chronic obstructive pulmonary disease and there are now several oral compounds currently in development for this disease, with encouraging data beginning to emerge. With an inhaled agent likely to improve the therapeutic window between efficacy and some of the common adverse events observed with oral p38 inhibitors it would seem a sensible approach to take for a disease of the lung. This review will highlight the potential for an inhaled p38 inhibitor in chronic obstructive pulmonary disease, as well as some of the design principles that are important to consider when developing an inhaled kinase inhibitor.
21860378 Induction and testing of hypoxia in cell culture. 2011 Aug 12 Hypoxia is defined as the reduction or lack of oxygen in organs, tissues, or cells. This decrease of oxygen tension can be due to a reduced supply in oxygen (causes include insufficient blood vessel network, defective blood vessel, and anemia) or to an increased consumption of oxygen relative to the supply (caused by a sudden higher cell proliferation rate). Hypoxia can be physiologic or pathologic such as in solid cancers, rheumatoid arthritis, atherosclerosis etc… Each tissues and cells have a different ability to adapt to this new condition. During hypoxia, hypoxia inducible factor alpha (HIF) is stabilized and regulates various genes such as those involved in angiogenesis or transport of oxygen. The stabilization of this protein is a hallmark of hypoxia, therefore detecting HIF is routinely used to screen for hypoxia. In this article, we propose two simple methods to induce hypoxia in mammalian cell cultures and simple tests to evaluate the hypoxic status of these cells.
21701078 Effect of methotrexate on fracture healing. 2011 Low doses of methotrexate (MTX) are safe and effective for treating adult and juvenile rheumatoid arthritis. However, because this powerful anti-inflammatory drug might negatively influence the healing of wounds and fractures, MTX administration is often stopped during surgical procedures. The present study assesses the effects of low- and high-dose MTX on early inflammatory processes and bone healing in an experimental model of fracture. Thirty male Sprague-Dawley rats were assigned to low- and high-dose MTX and control groups. A femur was cut using a reciprocating saw and a 2-mm fracture gap was made using a fixator. One or four weeks thereafter, macrophages were immunostained and new bone formation was histomorphometrically measured. Significantly less new bone was formed in the high-dose MTX, than in the control group (p< 0.01), whereas bone formation did not significantly differ between the low-dose MTX and control groups. These results suggested that a low dose of MTX does not affect the early process of endochondral bone formation during fracture healing, whereas a high dose might delay the progress of new periosteal bone formation. Although more macrophages were found in the groups treated with MTX, their impact on surrounding inflammatory processes remains unclear.
21637053 Clinical role of FDG PET/CT for methotrexate-related malignant lymphoma. 2011 Jul Methotrexate-related malignant lymphoma (MTX-RML) is a type of therapy-related lymphoma, and it often occurs in patients with rheumatoid arthritis. The most distinctive characteristic of MTX-RML is a quick response to withdrawal of MTX. However, because there is a risk of recurrence without a distinctive indicator of disease, close follow-up is needed. We present F-18 2-fluoro-2-deoxyglucose (FDG) postitron emission tomography (PET) or computed tomography (CT) images of MTX-RML along with the characteristic clinical presentation of MTX-RML. FDG PET/CT has the advantage of being able to detect malignant lymphoma in patients who have undergone MTX treatment. After withdrawal of MTX, FDG uptake decreases along with a reduction in the volume of lesions. Although recurrent lesion develops independent to the initial FDG PET/CT findings, FDG PET/CT is useful for early detection of unexpected recurrent lesions. FDG PET/CT allows for the assessment of malignant lymphoma and recurrent lesions in patients who received MTX therapy, which is crucial for the management of MTX-RML.
21372514 [Marked efficacy of metronidazole for the intestinal pseudoobstruction associated with sys 2011 In May 2009, a 57-year-old woman who had rheumatoid arthritis since 9 years was admitted to our hospital for dyspnea due to interstitial pneumonia (IP). On admission, she exhibited proximal scleroderma, finger edema, Raynaud's phenomenon, digital pitting scars, ankyloglossia, and esophageal dysmotility. The patient was diagnosed as having systemic sclerosis (SSc), according to the American College of Rheumatology criteria. After initiation of high-dose corticosteroid therapy, gradual amelioration of IP was observed. However, the patient complained of abdominal fullness. Computed tomography and intestine series findings revealed significant dilatation of the small intestine due to intra-abdominal free air and pneumatosis cystoides intestinalis but no mechanical obstruction, leading to a diagnosis of SSc with pseudo-obstruction. The patient underwent decompression with a long intestinal tube, which led to improvement in her symptoms. Although erythromycin (EM) and some prokinetic agents were administered, abdominal involvement recurred several days after resumption of oral ingestion. Therefore, we changed the antibiotic from EM to metronidazole (750 mg/day). Her manifestations were promptly ameliorated by metronidazole therapy in 4 days and did not recur. Metronidazole is an antibiotic used to treat intra-abdominal anaerobic bacterial infections and is also commonly used in preoperative treatment for colorectal surgery. In conclusion, we report a case where SSc-associated pseudo-obstruction was successfully managed by metronidazole therapy.
21369953 Silicone breast implants and connective tissue disease: no association. 2011 May The association of silicone breast implants with connective tissue diseases (CTDs), including systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and fibromyalgia, as well as a hypothesized new "atypical" disease, which does not meet established diagnostic criteria for any known CTD, has been extensively studied. We have reviewed the epidemiologic literature regarding an association between cosmetic breast implants and CTDs, with particular emphasis on results drawn from the most recent investigations, many of which are large cohort studies with long-term follow-up, as well as on those studies that address some of the misinformation and historically widespread claims regarding an association between breast implants and CTDs. These claims have been unequivocally refuted by the remarkably consistent evidence from published studies, as well as numerous independent meta-analyses and critical reviews, which have demonstrated that cosmetic breast implants are not associated with a subsequent increased occurrence of individual CTDs or all CTDs combined, including fibromyalgia. Moreover, there is no credible evidence for the conjectured excess of "atypical" CTD among women with cosmetic breast implants, or of a rheumatic symptom profile unique to these women. No increased risk of CTDs is evident in women with extracapsular ruptures in two studies, which evaluated risk by implant rupture status, and no consistent association has been observed between silicone breast implants and a variety of serologic markers or autoantibodies. Thus, any claims that remain regarding an association between cosmetic breast implants and CTDs are not supported by the scientific literature but rather are a residual byproduct of the unprecedented large-scale product liability litigation in the USA.
21255096 New targets of pemphigus vulgaris antibodies identified by protein array technology. 2011 Feb We performed partial evaluation of pemphigus vulgaris (PV) autoantibody profile using the protein array technology. The sera from seven patients with acute PV and five healthy donors were probed for the presence of autoantibodies characteristic of the organ-non-specific autoimmune disorders rheumatoid arthritis, lupus erythematosus, scleroderma, diabetes and some other autoimmune disorders, but not to desmosomal proteins. The array targeted 785 human genes amplified using Mammalian Gene Clone Collection with gene-specific primers containing 20-bp nucleotide extension complementary to ends of linear pXT7 vector. The array identified PV antibodies significantly (P<0.05) differentially reactive with 16 antigens, most of which were cell-surface proteins, such as CD2, CD31, CD33, CD36, CD37, CD40, CD54, CD66c and CD84 molecules, nicotinamide/nicotinic acid mononucleotide adenylyltransferase, immunoglobulin heavy chain constant region gamma 2 and others. Reactivity with Fc-IgG helps explain an ability of the chimeric desmoglein constructs to absorb out all disease-causing PV antibodies. Anti-M(1) muscarinic receptor antibody was also identified, consistent with the facts that while blockade of this receptor causes keratinocyte detachment, its activation is therapeutic in PV. Further proteomics analysis of PV antibodies should help elucidate the immunopathogenic mechanisms underlying keratinocyte detachment and blistering.
21204734 Therapeutic targeting of osteoclast function and pathways. 2011 Feb INTRODUCTION: Osteoclasts are responsible for bone resorption and underlie a number of pathological states in which osteolysis is a feature. Over recent decades our molecular understanding of osteoclast differentiation and activation has expanded significantly, and this has allowed for the development of a number of osteoclast-targeted therapies. AREAS COVERED: This review seeks to present the underlying molecular mechanisms of osteoclast differentiation and activity as a basis for understanding our current treatment of osteoporosis and malignant tumors in bone. Osteoclast-targeted therapies are also being evaluated for the treatment of rheumatoid arthritis, osteosarcoma and giant cell tumor of bone. EXPERT OPINION: With concurrent advances in the fields of molecular biology, pathology and advanced imaging, osteoclast-targeted therapies show great potential for treating conditions in which excess resorption of bone is a key pathological process. Targeting of osteoclast control mechanisms offers the potential of combining 'molecular imaging' with therapeutic intervention and longitudinal monitoring of disease processes.
21186199 Right coronary artery fistula to the coronary sinus and right atrium associated with giant 2011 Mar We present the case of a 54-year-old female with a previous history of lung fibrosis secondary to methotrexate used for rheumatoid arthritis who was referred to cardiology evaluation due to precordial pain. Echocardiography showed biatrial enlargement with an enlarged coronary sinus and tubular image posterior to the heart. On the coronary angiogram, the right coronary artery was enlarged, and a distal fistula was identified. The patient underwent a contrast enhanced cardiac computed tomography which demonstrated an aneurysmatic right coronary artery with a distal fistula to the right atrium and coronary sinus. As the chest pain did not recur and there was a high risk of the intervention to correct coronary fistula, the patient remained on conservative treatment.
21172874 The role of osteoclast-associated receptor in osteoimmunology. 2011 Jan 1 The term osteoimmunology is coined for molecular and cellular cross talk between the skeletal and immune system. Immunomodulatory signals have long been implicated as key regulators of bone metabolism. Recently, osteoclast-associated receptor (OSCAR), an IgG-like receptor, has been identified as an important osteoimmunological mediator. OSCAR expression in bone is highly conserved across different species, and the molecule is an important costimulatory receptor for osteoclast differentiation through activation of NFATc1. In humans, OSCAR is expressed by macrophages, monocytes, and monocyte-derived dendritic cells and modulates the response of the innate and adaptive immune systems by promoting cell activation and maturation, Ag presentation, and proinflammatory circuits. Human studies indicate that OSCAR may contribute to the pathogenesis and severity of osteoporosis and rheumatoid arthritis. In this paper, we review the structure-function relationship, expression pattern, and physiological role of OSCAR in osteoimmunology and summarize its potential implications for human diseases.
21107711 Interleukin-21 as a potential therapeutic target for systemic lupus erythematosus. 2011 Aug Interleukin-21(IL-21) is the most recently discovered member of the type-I cytokine family. Structurally, IL-21 shows homology to IL-2, 4, and 15 proteins. It has a variety of effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. Many previous studies have identified that IL-21 was associated with different autoimmune and inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. In addition, recent work has explored the role of IL-21 in systemic lupus erythematosus (SLE). Elevated expression of IL-21 was found in the sera of patients and mice with SLE. Moreover, association of IL-21 and IL-21R polymorphisms with susceptibility to SLE have been reported. All these findings suggest that IL-21 may have promise as a potential therapeutic target for SLE. In this review, we will discuss the biological features of IL-21, the IL-21 signaling and its potential role in SLE.
21079906 Hematopoietic colony-stimulating factors: new players in tumor-nerve interactions. 2011 Apr A variety of cancers are accompanied by debilitating pain, which constitutes the primary reason for poor quality of life in cancer patients. There is an urgent demand for the development of specific mechanism-based therapies against cancer pain. Recently, important advances have been made in mechanisms contributing to cancer pain. A notable finding was that the tumor-derived hematopoietic growth factors, granulocyte- and granulocyte-macrophage-colony-stimulating factors (G-CSF/GM-CSF), subserve important functions in the generation of pain hypersensitivity in tumor-affected regions. In this context, their receptors were unexpectedly found on pain-sensing nerves and were observed to be functionally linked to nociceptive sensitization and tumor-induced pain. Here, we review evidence supporting a role for G-/GM-CSF in sensitization of pain-sensing nerves, the underlying signaling pathways and the cross-talk with other pronociceptive cytokines, peptides and modulators derived from immune cells, osteoclasts and tumor cells. These findings hold implications in the therapy of pain in disease states, such as cancer and rheumatoid arthritis.
21030559 Increased thioredoxin-1 production in human naturally occurring regulatory T cells confers 2011 Jan 20 Levels of regulatory T cells (Tregs) are increased in different cancer types as well as in inflammatory diseases, such as rheumatoid arthritis. Treg accumulation may result from aberrant proliferation and trafficking as well as greater resilience to oxidative stress compared with conventional T cells. This enhanced antioxidative capacity of Tregs possibly serves as feedback inhibition during inflammation and prevents uncontrolled immune reactions by favoring survival of suppressor rather than effector cells. In this study, we demonstrate that human Tregs express and secrete higher levels of thioredoxin-1, a major antioxidative molecule. Thioredoxin-1 has an essential role in maintaining their surface thiol density as the first line of antioxidative defense mechanisms and is sensitive to proinflammatory stimuli, mainly tumor necrosis factor-α, in a nuclear factor-κB-dependent fashion. The antiapoptotic and oncogenic potential of (secreted) Trx-1 suggests that it may exert effects in Tregs beyond redox regulation.
20863903 Atherosclerosis and macrovascular involvement in systemic sclerosis: myth or reality. 2011 Mar Systemic sclerosis (SSc) is a chronic disease of unknown etiology, characterized by enhanced fibrosis, and microvascular abnormalities. During the past several decades, the death rates due to cardiovascular disease or cerebrovascular disease in SSc patients substantially increased and are currently responsible for 20-30% of mortality. Various autoimmune rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus accelerate atherosclerosis. Although microvascular disease is a hallmark of SSc, an ongoing debate exists regarding the presence and extent of macrovascular diseases and the presence of accelerated atherosclerosis in SSc patients. Despite conflicting results as to intima-media thickness (IMT) in SSc patients, the most recent and largest study has found no difference in either plaque occurrence or IMT. Additionally, abnormal coronary flow reserve in SSc patients appears to be due to microvascular involvement rather than atherosclerosis of the epicardial coronary arteries. Angiographic findings as well as computed tomography studies have generated conflicting reports as to coronary atherosclerosis in SSc. Herein, we review the current knowledge of macrovascular involvement and atherosclerosis in SSc. The differences between SSc and other autoimmune rheumatic diseases in the presence and extent of atherosclerosis need to be further investigated.
19855968 Dermatomyositis and HIV infection: case report and review of the literature. 2011 May Since the 1980s, a host of autoimmune phenomena and rheumatologic illnesses have been linked to infection with the human immunodeficiency virus (HIV). Given the broad effects of this virus on both the humoral and cell-mediated arms of the immune system, illnesses such as polymyositis and Reiter's syndrome appear to be more prevalent in HIV-infected individuals and occur in the absence of well-described predispositions. The activities of some rheumatologic illnesses exhibit an inverse relationship with the course of HIV infection, such as rheumatoid arthritis, which becomes more quiescent with advancing disease. Dermatomyositis is a rheumatologic illness that very infrequently occurs and during our review of literature only three other cases were reported. We present the case of a Caucasian male in his mid-20s who presented with acquired immunodeficiency syndrome and subsequently developed dermatomyositis. In this review, we highlight the current relationship between HIV infection and autoimmunity, the possible ways HIV infection may foster an environment favorable for the development of dermatomyositis, and review the previously reported cases of individuals with HIV infection who developed dermatomyositis. The complex issues of how to treat individuals with HIV and dermatomyositis is also discussed.