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ID PMID Title PublicationDate abstract
21179612 Atacicept: targeting B cells in multiple sclerosis. 2010 Jul Multiple sclerosis (MS) has traditionally been considered to be a T-cell-mediated disease. However, there is an increasing body of evidence for the involvement of B cells and autoantibodies in the pathology of this disease, providing a rationale for treatments directed against B cells. In this paper we summarize evidence for the key role of B cells in the immunopathology of MS and review data supporting the use of a novel B-cell targeted therapy, atacicept, in this condition. Atacicept is a human recombinant fusion protein that comprises the binding portion of a receptor for both BLyS (B-Lymphocyte Stimulator) and APRIL (A PRoliferation-Inducing Ligand), two cytokines that have been identified as important regulators of B-cell maturation, function and survival. Atacicept has shown selective effects on cells of the B-cell lineage, acting on mature B cells and blocking plasma cells and late stages of B-cell development while sparing B-cell progenitors and memory cells. The efficacy of atacicept in animal models of autoimmune disease and the biological activity of atacicept in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) has been demonstrated. Clinical studies were initiated to investigate the safety, tolerability and efficacy of atacicept in patients with MS. An unexpected increase in inflammatory activity in one of the trials, however, led to suspension of all atacicept trials in MS.
20807507 Transmission of circulating cell-free AA amyloid oligomers in exosomes vectors via a prion 2010 Oct 1 Recent studies clearly demonstrated that several types of pathogenic amyloid proteins acted as agents that could transmit amyloidosis by means of a prion-like mechanism. Systemic AA amyloidosis is one of the most severe complications of chronic inflammatory disorders, particularly rheumatoid arthritis. It is well known that, similar to an infectious prion protein, amyloid-enhancing factor (AEF) acts as a transmissible agent in AA amyloidosis. However, how AEF transmits AA amyloidosis in vivo remained to be fully elucidated. In the present study, we focused on finding cell-free forms of AEF and its carriers in circulation by using the murine transfer model of AA amyloidosis. We first determined that circulating cell-free AEF existed in blood and plasma in mice with systemic AA amyloidosis. Second, we established that plasma exosomes containing AA amyloid oligomers derived from serum amyloid A had AEF activity and could transmit systemic AA amyloidosis via a prion-like mechanism. These novel findings should provide insights into the transmission mechanism of systemic amyloidoses.
20722620 Alternative use of bisphosphonate therapy for rheumatic disease. 2010 Bisphosphonates are widely use for pathologies such as osteoporosis, Paget's disease or bone metastasis. However, their potent antiresorptive properties open new therapeutic opportunities for other conditions associated with an increased focal or systemic bone remodelling. Moreover, apart from their antiresorptive activity, bisphosphonates could also have others properties through a specific analgesic or anti-inflammatory effect. Thus, rheumatic diseases like rheumatoid arthritis, spondylarthritis or SAPHO syndrome (acronym for synovitis, acne, pustulosis, hyperostosis and osteitis) that are associated with systemic and sometimes focal bone loss could be good candidates for bisphosphonate therapy. Other non-inflammatory rheumatic diseases like bone osteonecrosis, algodystrophy, fibrous dysplasia or neuropathic osteoarthropathy are also associated with pain and an increase of focal bone remodelling. Several studies have shown that bisphosphonate could have promising therapeutic potential in these inflammatory or non-inflammatory diseases where therapeutic options are usually few. This review will focus on the new potential alternative indications for bisphosphonate in rheumatic diseases.
20550723 Rituximab ameliorated severe hearing loss in Cogan's syndrome: a case report. 2010 Jun 16 BACKGROUND: Rituximab is a monoclonal antibody inducing depletion of B lymphocytes and presently approved for the treatment of non-Hodgkin's lymphoma and rheumatoid arthritis. Here is the first report of the use of this drug in a case of Cogan's syndrome (CS). CASE PRESENTATION: a 25-year-old Italian woman was referred with conjunctival hyperaemia, interstitial keratitis, moderate bilateral sensorineural hearing loss accompanied by tinnitus, dizziness, nausea and vertigo, poorly responsive to oral and topical steroidal therapy. Diagnosis of typical CS was made. The administration of a combined immunosuppressive treatment resolved ocular inflammation, dizziness, nausea, and vertigo but gave little results in controlling progressive hearing loss. A noticeable improvement in hearing function was documented by pure tone audiometry after infusion of Rituximab. DISCUSSION: in CS, hearing function is often the most difficult parameter to control with therapy. A positive effect of Rituximab on was observed in our case. The drug also allowed to significantly reduce the number of adjuvant immunosuppressive medications.
20514324 A case of hypertrophic cranial pachymeningitis presenting with scleritis in a patient with 2010 Jun Hypertrophic cranial pachymeningitis (HCP) is an uncommon disorder that causes a localized or diffuse thickening of the dura mater and has been reported to be infrequently associated with systemic autoimmune disorders such as Wegener's granulomatosis, rheumatoid arthritis, sarcoidosis, Behçet's disease, Sjögren syndrome, and temporal arteritis. Here, we report a case of HCP initially presented with scleritis and headache in a patient with undifferentiated connective tissue disease (UCTD). HCP was initially suspected on brain magnetic resonance imaging and defined pathologically on meningial biopsy. Immunologic studies showed the presence of anti-RNP antibody. After high dose corticosteroid therapy, the patient's symptoms and radiologic abnormalities of brain were improved. Our case suggested that HCP should be considered in the differential diagnosis of headache in a patient with UCTD presenting with scleritis.
20411808 [Case of toxoplasma encephalopathy with specific MRI findings, diagnosed by IgG avidity in 2010 Apr We report a 60-year-old woman with toxoplasma encephalopathy. She was being treated with prednisolone and methotrexate for rheumatoid arthritis that was diagnosed at the age of 40. In a preoperative examination of her left fifth finger ganglion, pericardial effusions, cardiomegaly, and a right atrial mass were detected. In addition, brain MRI showed nodular shadows in the right thalamus, bilateral globus pallidus, and left dentate nucleus of the cerebellum. T1 and T2 weighted images showed high intensities within those shadows; however, a T1 gadolinium enhancement image showed no contrast enhancement in the lesions. There were no positive neurological findings. Examination of the cerebrospinal fluid and cultivation tests showed nothing particular. The right atrial mass was subsequently diagnosed as malignant lymphoma and treated with radiation therapy. Toxoplasma gondii antibody titers were increased in both serum and cerebrospinal fluid. Based on IgG avidity index and nested PCR, we diagnosed toxoplasma encephalopathy with chronic T. gondii infection. The T. gondii gene product was also detected in cerebrospinal fluid by nested PCR. We consider that IgG avidity index and nested PCR were useful for the diagnosis of toxoplasma encephalopathy.
20356400 Differing effect of systemic anti psoriasis therapies on platelet physiology--a case repor 2010 Mar 31 BACKGROUND: Psoriasis is a common, chronic relapsing inflammatory skin disease. Lately, there is increasing evidence that psoriasis is more than "skin deep". Epidemiological studies showed that severe psoriasis might have also important systemic manifestations such as metabolic deregulations, cardiovascular disease (CVD) and increased mortality. Moreover, recently psoriasis patients were found to have platelet hyperactivity. CASE PRESENTATION: This is a case report and review of the literature. We present a patient with long standing severe psoriasis vulgaris with marked thrombocytosis. His thrombocytosis did not correlate with disease severity but rather with the different treatments that he was exposed to, subsiding only during treatment with anti Tumor Necrosis Factor (TNF)- agents. A literature review revealed that in rheumatoid arthritis, another systemic inflammatory disease; interleukin (IL)-6 might be implicated in causing thrombocytosis. CONCLUSION: This unique case report illustrates that different systemic treatments for psoriasis might have implications beyond the care of skin lesions. This insight is especially important in psoriasis patients in view of their deranged hemostatic balance toward a prothrombotic state, which might increase the risk of thrombosis and CVD. Therefore, further studies analyzing the effect of different drugs on platelets physiology are warranted.
20176259 Immunologic rheumatic disorders. 2010 Feb We provide the basics for clinicians who might be called on to consider the diagnosis of diseases such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) in their practice. We will emphasize clinical recognition and first-line laboratory testing. Only characteristics of the classic rheumatic inflammatory diseases (ie, RA, seronegative spondyloarthropathy, SLE, antiphospholipid syndrome, Sjögren syndrome, scleroderma, and polymyositis/dermatomyositis) will be covered. In the past decade, treatment for RA and seronegative spondyloarthropathy has substantially improved. Their treatment has been revolutionized by the use of methotrexate and, more recently, TNF inhibitors, T-cell costimulation modulators, and B-cell depletion. The goal of RA treatment today is to induce a complete remission as early as possible in the disease process, with the mantra being "elimination of synovitis equals elimination of joint destruction." The hope is that if the major mediators of Sjögren syndrome, SLE, or scleroderma can be identified and then blocked, as in the example of TNF inhibitors in patients with RA, more specific treatments will become available. Thus RA has become an excellent model of this evolving paradigm. Through the identification of major mediators in its pathogenesis, novel and highly efficacious therapeutic agents have been developed.
20134490 Top-down therapy for IBD: rationale and requisite evidence. 2010 Feb Several trials have shown that early treatment of Crohn's disease with immunomodulators and anti-TNF agents leads to a superior clinical outcome, including healing of the mucosa, compared with standard therapy alone. Mounting evidence indicates that mucosal healing is associated with a reduced risk of complications, and a reduced need for surgeries and hospitalizations. In the SONIC trial, a combination of the standard azathioprine immunomodulator therapy and infliximab, an anti-TNF agent, had more potent anti-inflammatory effects than either drug alone in patients with Crohn's disease who had evidence of active inflammation. These findings and those from rheumatoid arthritis trials have prompted the investigation of early initiation of immunomodulator (standard or anti-TNF) therapy for Crohn's disease, in suitable patients, which has led to substantial improvements in disease management. Careful selection of patients is, however, essential given the potential risk of toxic effects from these therapies and the fact that some patients with IBD will have a favorable disease course without them. Identification of suitable patients, however, remains a challenge, as genetic, phenotypic and environmental factors have not yet been identified that can be used for routine assessment and selection is mainly based on clinical criteria.
20053532 Epigenetics and autoimmunity. 2010 May Advances in genetics, such as sequencing of the human genome, have contributed to identification of susceptible genetic patterns in autoimmune diseases (AID). However, genetics is only one aspect of the diseases that does not reflect the influence of environment, sex or aging. Epigenetics, the control of gene packaging and expression independent of alterations in the DNA sequence, is providing new directions linking genetics and environmental factors. Recent findings have contributed to our understanding of how epigenetic modifications could influence AID development, showing differences between AID patients and healthy controls but also showing how one disease differs from another. With regards to epigenetic abnormalities, DNA methylation and histone modifications could be affected leading to large spatial and temporal changes in gene regulation. Other epigenetic processes, such as the influence of the ionic milieu around chromatin and DNA supercoiling stresses may be suspected also. The newly described role of microRNAs in control of gene expression is important by promoting or suppressing autoreactivity in AID. As a consequence control of cellular processes is affected becoming conducive, for example, to the development of autoreactive lymphocytes in systemic lupus erythematosus, synoviocyte proliferation in rheumatoid arthritis, or neural demyelination in multiple sclerosis. Application of epigenetics to AID is in its infancy and requires new hypotheses, techniques, tools, and collaborations between basic epigenetic researchers and autoimmune researchers in order to improve our comprehension of AID. From this will arise new therapeutics, means for early intervention, and perhaps prevention.
19794918 Prevention of NSAID-Induced Small Intestinal Mucosal Injury: Prophylactic Potential of Lan 2009 Sep Non-steroidal anti-inflammatory drugs (NSAIDs), which are used for the treatment of several inflammatory disorders including rheumatoid arthritis, are well known to cause gastroduodenal mucosal lesions as an adverse effect. Recently, the serious problem of NSAID-induced small intestinal damage has become a topic of great interest to gastroenterologists, since capsule endoscopy and double-balloon enteroscopy are available for the detection of small intestinal lesions. Such lesions have been of great concern in clinical settings, and their treatment and prevention must be devised as soon as possible. Proton pump inhibitors (PPI), such as lansoprazole and omeprazole, show a potent anti-secretory effect. PPIs also have a gastroprotective effect, independent of their anti-secretory actions, which is probably mediated by inhibition of neutrophil functions as well as antioxidant actions. Administration of lansoprazole reduced the severity of the intestinal lesions in a dose-dependent manner, but omeprazole had no effect. The amount of heme oxygenase-1 (HO-1) protein in the intestinal mucosa was significantly increased by lansoprazole, but not by omeprazole. These results suggest that lansoprazole, but not omeprazole, ameliorates indomethacin-induced small intestinal ulceration through upregulation of HO-1/carbon monoxide. Therefore, lansoprazole may be useful for preventing the adverse effects of NSAIDs not only in the stomach but also in the small intestine.
19773741 Accepting risk in clinical research: is the gene therapy field becoming too risk-averse? 2009 Nov Risk is an inescapable aspect of clinical research and is increasingly pertinent to the gene therapy field as the imperative for clinical trial activity grows. In recent years, the widely reported occurrence of serious adverse events (SAEs) in gene therapy studies, including trials for ornithine transcarbamylase (OTC) deficiency, X-linked severe combined immunodeficiency (SCID-X1), and rheumatoid arthritis, has heightened fear in public perceptions of gene therapy. Although it is essential to be cognizant of the risks involved in gene therapy research, there is a danger that gene therapy may become too risk-averse. If the field is to make progress, it is necessary to understand how risk is defined in gene therapy research, how understandings of risk differ, how risk is assessed, how decisions about risk are made, and how gene therapy risks are communicated to subjects and research participants during the informed consent process. In addition to minimizing the risks of clinical research through extensive preclinical safety studies, attention should be given to how decisions about risk and risk acceptability are made by researchers and subjects, and to the methods used to communicate risks to patients. Critical attention to risk will help ensure that the safety of subjects is protected, while also enabling research to develop better treatments for patients.
19726993 Exercise as an anti-inflammatory intervention to combat inflammatory diseases of muscle. 2009 Nov PURPOSE OF REVIEW: The purpose of this review was to give an update on the effects of physical exercise in patients with chronic inflammatory disorders with a focus on the potential anti-inflammatory effects, particularly in inflammatory myopathies. RECENT FINDINGS: Until recently patients with myositis were refrained from doing physical exercise due to the fear of exacerbation of muscle inflammation. Several studies now support the beneficial clinical effects of physical exercise on physical performance, cardiorespiratory fitness and muscle strength in these patients. In this context, the observations from healthy individuals and from patients with other chronic inflammatory disorders such as rheumatoid arthritis and chronic obstructive lung disease that physical exercise or regular physical activity may lower levels of systemic inflammation markers such as C-reactive protein (CRP) and interleukin (IL) 6 is interesting. Exercise may also have a downregulating effect on inflammatory molecules in muscle tissue, which is of particular relevance for patients with myositis. Thus, physical activity or exercise can have a beneficial effect on human health partly due to its anti-inflammatory effect. SUMMARY: In contrast to the previous recommendations to avoid physical exercise, accumulating data now suggest that physical exercise in patients with myositis is safe, benefits clinical outcome and may even reduce inflammation.
19678540 The interleukin-18 inhibitory activities of echinocystic acid and its saponins from Impati 2009 May Echinocystic acid (1), an echinocystic acid saponin, 2, and four of its ester saponins, 3-6, obtained from the active fraction of Impatiens pritzellii var. hupehensis, an traditional Chinese medicine for rheumatoid arthritis, were investigated for their effects on lipopolysaccharide (LPS)-induced interleukin (IL)-18 in human peripheral blood mononuclear cells. Three of them, 1, 2 and 6, showed obvious activity to inhibit the production of IL-18, especially the ester saponins with a sugar chain at C-28, 6. Structure-activity relationships are discussed in brief.
19546580 Genetics of diabetic nephropathy: are there clues to the understanding of common kidney di 2009 Diabetic nephropathy is the most common cause of end-stage renal disease in the Western world. There is evidence for a genetic susceptibility to diabetic kidney disease, but despite intensive research efforts it has proved difficult to identify the causative genes. Improvements in genotyping technologies have made genome-wide association studies (GWAS), employing hundreds of thousands of single nucleotide polymorphisms, affordable. Recently, such scans have advanced understanding of the genetics of common complex diseases, finding more than 100 novel susceptibility variants for diverse disorders including type 1 and 2 diabetes, coronary heart disease, Crohn's disease and rheumatoid arthritis. In this review, type 2 diabetes is highlighted to illustrate how genome-wide association studies have been used to study the genetics of complex multifactorial conditions; in addition, diabetic nephropathy will be used to demonstrate how similar scans could be employed to detect genetic factors predisposing to kidney disease. The identification of such variants would permit early identification of atrisk patients, enabling targeting of therapy and a move towards primary prevention. In addition, these powerful research methodologies may identify genes that were not previously known to predispose to nephropathy, thereby enhancing our understanding of the pathophysiology of renal disorders and potentially leading to novel therapeutic approaches.
19513730 [Translational aspects on the role of B-cells in autoimmune diseases. "From bench to bedsi 2009 Jul In recent years, new findings in immunology have been successfully converted to therapeutic principles, in particular for rheumatoid arthritis (RA) and spondylarthritides. The introduction of cytokine blockers in RA using tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 inhibitors presented the first original therapy modalities in rheumatology, after proliferation-inhibiting drugs, such as methotrexate and cyclophosphamide, had been accepted in oncology. This advance was and is still being extended with the co-stimulation blockade using abatacept and IL-6 receptor inhibition. Anti-CD20 therapies are of particular importance, initially approved for the treatment of non-Hodgkin's lymphoma (NHL), this therapy modality has been approved in recent years for the treatment of RA following the failure of TNF-blockade. However, questions remain regarding the role of B cells in a number of autoimmune diseases, as well as the working principles of B-cell targeted therapy. In this context, close clinical observation of patients has yielded answers to and confirmation of basic scientific concepts.
20333321 Anti-Inflammatory Agents for Cancer Therapy. 2009 Inflammation is closely linked to cancer, and many anti-cancer agents are also used to treat inflammatory diseases, such as rheumatoid arthritis. Moreover, chronic inflammation increases the risk for various cancers, indicating that eliminating inflammation may represent a valid strategy for cancer prevention and therapy. This article explores the relationship between inflammation and cancer with an emphasis on epidemiological evidence, summarizes the current use of anti-inflammatory agents for cancer prevention and therapy, and describes the mechanisms underlying the anti-cancer effects of anti-inflammatory agents. Since monotherapy is generally insufficient for treating cancer, the combined use of anti-inflammatory agents and conventional cancer therapy is also a focal point in discussion. In addition, we also briefly describe future directions that should be explored for anti-cancer anti-inflammatory agents.
19093325 Sarcoidosis and the rheumatologist. 2009 Jan PURPOSE OF REVIEW: The purpose of this review is to discuss challenges in the diagnosis and treatment of sarcoidosis by rheumatologists. RECENT FINDINGS: Sarcoidosis is a heterogeneous multisystem granulomatous disease. Rheumatologists are faced with multiple challenges in the management of this disease. Features that can have similarities to many rheumatic diseases are being increasingly reported. There are many reports of sarcoidosis coexisting with or mimicking rheumatic diseases such as systemic lupus erythematosus, rheumatoid arthritis, and ankylosing spondylitis. Musculoskeletal features of sarcoidosis can also mimic infection and malignancy. Biomarkers for the diagnosis and monitoring of treatment of response are lacking. Tumor necrosis factor (TNF) inhibition therapy is a viable alternative for immunodulation for various manifestations. However, increased vigilance is needed, as there are also emerging reports of drug-induced sarcoidosis in association with the use of anti-TNFalpha agents and other medications. This article reviews these diagnostic and treatment challenges that rheumatologists face. SUMMARY: Many questions remain to be answered. More studies looking at the reliability of certain serological and radiological biomarkers are needed. Issues concerning the safety of the use of biological response modifiers in inducing sarcoidosis need further study.
21099241 [A case of psoriasis induced by infliximab treatment for Crohn's disease]. 2010 Nov Infliximab, the monoclonal antibody to tumor necrosis factor, is indicated for refractory luminal and fistulizing Crohn's disease and rheumatoid arthritis. Infliximab treatment has adverse events including infusion reactions, opportunistic infections, and the potential for the event such as reactivation of latent tuberculosis. Cutaneous adverse reactions of TNF-α agents include skin rash, urticaria, pruritus, lupus-like eruption, and injection site reactions. Most of all, psoriasis or psoriasiform dermatitis induced by infliximab treatment for Crohn's disease is rarely reported in Korea. We report a case of psoriasis induced by infliximab treatment for Crohn's disease with a review of world literature.
20954790 Spiro azepane-oxazolidinones as Kv1.3 potassium channel blockers: WO2010066840. 2010 Dec This article evaluates a patent application from Solvay Pharmaceuticals, which claims spiro azepane-oxazolidinones as novel blockers of the voltage-gated potassium channel Kv1.3 for the treatment of diabetes, psoriasis, obesity, transplant rejection and T-cell mediated autoimmune diseases such as rheumatoid arthritis and MS. The patent describes a new chemotype of Kv1.3 blockers and thus illustrates the growing interest of the pharmaceutical industry in Kv1.3 as a target of immunosuppression and metabolic disorders. This article briefly summarizes the chemistry and biological data provided in the patent and then compares the new compounds to Kv1.3 blockers previously disclosed by both academia and pharmaceutical companies.