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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
18578973 Sarcoidosis occuring during anti-TNF-alpha treatment for inflammatory rheumatic diseases: 2008 May Anti-TNF-alpha agents have been tried in cases of refractory sarcoidosis, giving favourable results. Thus, the occurrence of a granulomatous disease in a patient receiving such drug seems paradoxical. We describe 2 patients with inflammatory rheumatic disease, the first with ankylosing spondylitis, the second with rheumatoid arthritis, under anti-TNF-alpha treatment (infliximab and etanercept respectively) who developed non-caseating granulomas of the lungs and lymph nodes consistent with the diagnosis of sarcoidosis. Limited and various similar cases have been reported. It is generally considered that these granulomatous diseases are related to the anti-TNF-alpha agent.
18450273 [Proposal of Croatian Society for Rheumatology for anti-TNF-alpha therapy in adult patient 2007 Spondyloarthritides (SpA) as a group are one of the most common rheumatic disorders with a predominant affection of the spine. Conventinal disease modifying antirheumatic drugs which are effective in rheumatoid arthritis have poor effect on spinal inflammation. Today there is confirmed efficacy ofbiologics in spondylitis. This therapy is expensive and potentially hazaradous. Croatian Society for Rheumatology set up recommendations for the use of TNF-alpha blockers in SpA. There are several important points to be considered before their use: diagnosis of Spa, duration and disease activity, previous therapy and it's efficacy, application and efficacy ofbiologics, contraindications and safety preacutions and finally a decision for continuous tretament with biologics.
18446139 Primer: Toll-like receptor signaling pathways--what do rheumatologists need to know? 2008 Jun Toll-like receptors (TLRs) have caught the attention of rheumatologists searching for additional therapeutic targets for diseases such as rheumatoid arthritis and systemic lupus erythematosus. Signaling from these molecules can induce the expression of cytokines such as tumor necrosis factor and interferon alpha. Strategies that target TLRs and their co-receptors (such as MD2 for TLR4 or CD36 for TLR2) might be a more-selective approach than inhibition of global signals such as nuclear factor kappaB or p38 mitogen-activated protein kinase. TLR signaling requires adaptor proteins, including MyD88, Mal, TRIF and TRAM, which are recruited to specific receptors: Mal is used only by TLR2 and TLR4, TRIF is used by TLR3 and TLR4, and TRAM is recruited by TLR4 alone. Mal and TRAM are subject to complex biochemical regulation. Inhibition of Mal or MyD88 blocks the production of inflammatory mediators in synovial tissue. Another possible intracellular target is Unc93b, a protein involved in signaling from TLR3, TLR7 and TLR9. Inhibition of TLR4, TLR7 and TLR9 has produced intriguing results, which indicate that TLRs and their signaling pathways might indeed have great potential as novel targets for the treatment of inflammatory joint disease.
18433881 Parental non-inherited HLA resistance alleles do not confer protection against multiple sc 2008 May 30 Multiple sclerosis (MS) is a complex trait in which alleles at or near the class II loci HLA-DRB1 and HLA-DQB1 contribute significantly to genetic risk. HLA-DRB1*14 and DRB1*11 bearing haplotypes protect against MS and DRB1*01 and DRB1*10 interact with DRB1*15 to reduce risk of the disease. Recent work in other autoimmune diseases such as rheumatoid arthritis has suggested that maternal non-transmitted protective alleles can also confer disease resistance. In this investigation of 7093 individuals from 1432 MS families, we have analysed the transmission of HLA-DRB1*14,*11,*10 and *01 haplotypes, stratified by sex of parent. No significant transmission differences between mothers and fathers were found, suggesting that non-inherited resistance alleles do not appear to play a role in MS.
18385630 Determinants of disability in chronic musculoskeletal health conditions: a literature revi 2008 Mar Knowledge of the determinants of disability in musculoskeletal conditions (MSC) is critical for reducing their burden. No epidemiologic studies from a truly comprehensive perspective consider environmental factors (EF) and personal factors (PF) as determinants of disability. However, one can identify candidate EF from the International Classification of Functioning, Disability and Health (ICF) Core Sets for rheumatoid arthritis (RA), osteoporosis (OP), osteoarthritis (OA), low back pain (LBP) and chronic wide spread pain (CWP). The objective of this literature review was to contribute to the validation of the EF from the ICF Core Sets for MSC and the candidate PF from a (ICF) Delphi exercise, as well as from the report of the Bone and Joint Decade (BJD) Health Strategy Project. The results of the literature search focus on reviews published between January 1991 and March 2006 that contained information on EF and PF that determine disability in LBP, RA and OA. Many PF and EF included in the ICF Core Sets were confirmed as potential determinants of disability. However, regarding some contextual factors, in particular EF referring to the physical environment, there is a lack of reviews and clinical studies that have investigated their relevance to disability. The predominant medical model in studies on disability in MSC may explain this lack of evidence. However, the increasing attention given to the integrative model of functioning, disability and health of the World Health Organization (WHO) and the approval of the ICF by the World Health Assembly in 2001 may stimulate future research on the effect of EF and PF on disability.
18285764 Technology Insight: hematopoietic stem cell transplantation for systemic rheumatic disease 2008 Apr Hematopoietic stem cells (HSCs) have the capacity for self-renewal and the potential to differentiate into all types of hematopoietic and immune system cells. These features have been successfully used to treat a multitude of hematologic malignancies and nonmalignant diseases such as aplastic anemia, hemoglobinopathies, inborn errors of metabolism and congenital immunodeficiency states. The application of HSC transplantation has been expanded over the past decade to include immune-mediated diseases such as multiple sclerosis, treatment-refractory rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. Transplantation of HSCs for the treatment of autoimmune diseases aims to fundamentally correct the dysregulated immune system, which could result in sustained clinical remission or potential cure. The use of this approach is currently restricted to clinical research, as there is no standard conditioning regimen to attain these aims in autoimmune diseases. HSC transplantation is associated with inherent morbidity and mortality, both treatment-related and disease-related, and selecting the correct group of patients with the best risk:benefit ratio is a challenging task.
18284649 Review article: use of antitumour necrosis factor therapy in inflammatory bowel disease du 2008 May BACKGROUND: One of the most frequently asked questions during consultation with those affected by inflammatory bowel disease is what are its effects on pregnancy, and how the treatment will impact on conception and pregnancy outcomes. AIM: To review available data regarding the safety of biological therapies during pregnancy, primarily in woman with inflammatory bowel disease. METHODS: A Medline search was performed and available original research and review articles relating to the use of biological (antitumour necrosis factor-alpha) therapies in inflammatory bowel disease were reviewed. Where information regarding the use of a drug in inflammatory bowel disease during pregnancy was limited, articles referring to its use for other indications, such as rheumatoid arthritis, were reviewed. CONCLUSIONS: Based on available data, biological therapies appear to be safe in pregnancy. Most studies looking at the effects of any one medication on pregnancy in inflammatory bowel disease are confounded by the fact that most patients are on multiple medications and have varying levels of disease activity. Stopping therapy in the third trimester should be considered. Large registries with longer follow-up periods will be necessary before firm conclusions about the safety of antitumour necrosis factor-alpha therapies during conception and pregnancy can be drawn.
18240539 Osteoporosis and inflammation. 2007 Dec Osteoporosis represents a major healthcare burden, affecting approximately 10 million people aged over 50 years in the United States and with another 30 million or more at risk. One of the major contributing factors to osteoporosis is withdrawal of estrogen during menopause in women. Human and animal experiments have implicated pro-inflammatory cytokines as primary mediators of the accelerated bone loss at menopause including interleukin-1, tumor necrosis factor-alpha, and interleukin-6. Increased production of pro-inflammatory cytokines is associated with osteoclastic bone resorption in a number of disease states including rheumatoid arthritis, periodontitis, and multiple myeloma; estrogen withdrawal is associated with increased production of pro-inflammatory cytokines, and exposure of bone cultures to supernatants from activated leukocytes is associated with increased bone resorption. A major advance has been the discovery of RANKL, its receptor RANK, and the endogenous inhibitor osteoprotegerin. The binding of RANKL to RANK is essential for the differentiation and activation of osteoclasts and mediates the actions of essentially all known stimulators of osteoclastic bone resorption. RANKL expression is heightened in post- compared with pre-menopausal women, and this effect is attenuated by estrogen replacement therapy. RANKL is also a therapeutic target; a human antibody with high specificity and affinity to RANKL is currently under clinical evaluation for the treatment of osteoporosis in post-menopausal women and of metastatic bone disease in cancer patients with bone metastasis. Early data are promising.
18090867 Temporal relationship between antitumor necrosis factor-alpha antibody therapy and recrude 2008 Mar Tumor necrosis factor (TNF)-alpha inhibitors have been used effectively to treat rheumatoid arthritis and inflammatory bowel disease. Although the role of TNF-alpha in tumor development is not well understood, an increased risk of malignancies with anti-TNF-alpha therapy has been suggested. We report an instructive case of a patient, treated for Crohn's disease with infliximab, who presented with a neck abscess diagnosed to be head and neck squamous cell carcinoma. The patient's clinical course illustrates a temporal relationship between reappearance of his cancer after a complete response to therapy and the resumption of infliximab for worsening Crohn's disease.
18065143 Adherence to therapy: using an evidence-based protocol. 2007 Nov The number of patients receiving injectable medications has increased significantly during the past few years. Today, patients with hepatitis, rheumatoid arthritis, and multiple sclerosis are added to the list of those, namely diabetics, who have been instructed in self-administration of injectable medications. Currently, some of these medications create significant skin site reactions, and patients tend to discontinue the medications without informing the healthcare provider. Determining the problem and developing a research study that provides evidence to demonstrate methods to help patients adhere to agreed-upon treatment modalities can be accomplished within the clinical practice setting. This study provided a method to decrease skin reactions with interferon 1-b injections for multiple sclerosis patients and has been continued as a method with other like medications.
17936213 Rituximab in mixed cryoglobulinemia: increased experience and perspectives. 2007 Sep Type II mixed cryoglobulinemia syndrome (MCsn) is a systemic vasculitis mainly linked to immune complex deposition in several organs and to hepatitis C virus (HCV) infection. Therapeutic strategies can target either the viral trigger HCV if present, or pathogenic events downstream the triggering infection, e.g, the proliferating B-cells directly. Antiviral therapy should be considered as first-line treatment in many HCV-positive patients. However, it may prove ineffective, contraindicated, or poorly tolerated. On the other hand, the other available treatments (such as cytotoxic agents, plasma exchange and steroids) may lead to life-threatening complications and may be difficult to manage in the long term. Given the good safety profile in lymphomas, rituximab (RTX) has been used off-label for numerous patients suffering from a variety of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis/ polymyositis, and anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis. Efficacy and safety of RTX in MCsn and in particular in MCsn-related glomerulonephritis was recently described. Based on these results, a multicentre, controlled, randomised, clinical trial is now ongoing to compare RTX versus the best available treatments in some severe MCsn manifestations (i.e. skin ulcers, sensory and/or motor neuropathy and active glomerulonephritis).
17873600 Reassessment of the role of cannabinoids in the management of pain. 2007 Oct PURPOSE OF REVIEW: The aim of this article is to assess the role of cannabinoids in the treatment of acute and chronic pain in humans. RECENT FINDINGS: Very few clinical trials looking at the analgesic effects of cannabinoids in the acute pain settings have been performed. Three recent studies have evaluated the oral administration of synthetic cannabinoids in postoperative pain. At low doses cannabinoids are not different from placebo, whereas at high doses they may be associated with adverse effects or even worsening of pain intensity. In chronic pain patients, the safety and analgesic efficacy of a number of cannabinoid compounds have recently been evaluated in several clinical trials in several chronic pain conditions. While the small size of the trials and the relatively short duration of follow-up limits broad generalization, to date there is increasing evidence that cannabinoids are safe and effective for refractory chronic pain conditions including neuropathic pain associated with multiple sclerosis, rheumatoid arthritis, and peripheral neuropathy associated with HIV/AIDS. SUMMARY: The precise role of cannabinoids in pain treatment still needs further evaluation. Cannabinoid compounds may be more effective in the context of chronic neuropathic pain than for the management of acute pain.
17762462 Basic science for the clinician 45: CD4+ T-cell subsets of probable clinical consequence. 2007 Aug I have often said "blessed be the splitters, for they shall inherit the earth." By that I mean that it is only by studying carefully culled populations, approaching, but never quite reaching, homogeneity that we can ever gain real insights into rheumatologic diseases. Differentiating tuberculous from gouty from rheumatoid arthritis was a good start, and when Moll and Wright identified the seronegative spondyloarthropathies, we were on our way to establishing "splitters" as leaders. Predictably, once T cells were identified as different from B cells, the floodgates opened. Subsets galore were described, with more isolated populations in the T-cell family, but we are now finding heterogeneity in B-cell populations, as well, which has been discussed in a previous article in this series. But as for T cells... well, it has not been smooth sailing. I initially trained in a laboratory that was firmly committed to the proposition that there were within the CD8 population not only cytotoxic cells but also "suppressor cells." Problem is, no one could ever isolate the little buggers, and so the idea of a suppressor or regulatory subpopulation of CD8+ T cells went the way of the Edsel. As noted in a previous article in this series, T regulatory cells were finally identified but not within the CD8+ population. And there are other regulatory subsets within both CD4+ and CD8+ T-cells populations and even new effector and memory populations that can be identified by their surface markers and functions. It is high time to review some of them; some of these populations may be involved in the immunopathogenesis of our diseases and undoubtedly will shortly be targets of immunotherapeutics. Although previous articles in this series discussed some of these subsets, I thought expanding on what is known about another recently described subset and putting them all together in one review might be helpful.
17727320 B-cell targeting: a novel approach to immune intervention today and tomorrow. 2007 Sep B cells and their products, antibodies, play an important role in the diagnosis and, in some instances, in the pathogenesis of many autoimmune diseases. Specific B-cell directed therapies are of recent interest as their impact on B-cell activity can influence a variety of autoimmune diseases. The development and introduction of rituximab, a depleting antibody targeting CD20+ B cells, and previously CD52-directed treatment with Campath-1h for the treatment of B-cell malignancies as well as rheumatoid arthritis have pioneered this therapeutic field. Other non-depleting strategies employ CD22 or B-cell activating factor/B lymphocyte stimulator and apoptosis-inducing ligand as targets and are under clinical investigation at present. Abnormalities of B-cell subsets have been identified by a number of independent groups which often represent characteristic patterns of disturbances of the human B-cell repertoire. However, the clinical value of specific B-cell subset targeting/depletion has not been addressed extensively. As such an approach may afford the possibility to avoid unnecessary adverse events related to depletion of non-pathogenic B-cell populations, B-cell subset targeting may have the capacity to enhance the benefit/risk ratio of B-cell immune intervention.
17614359 Nanosystems for simultaneous imaging and drug delivery to T cells. 2007 Jun 8 The T-cell response defines the pathogenesis of many common chronic disease states, including diabetes, rheumatoid arthritis, and transplant rejection. Therefore, a diagnostic strategy that visualizes this response can potentially lead to early therapeutic intervention, avoiding catastrophic organ failure or prolonged sickness. In addition, the means to deliver a drug dose to those cells in situ with the same specificity used to image those cells would provide for a powerful therapeutic alternative for many disease states involving T cells. In this report, we review emerging nanosystems that can be used for simultaneous tracking and drug delivery to those cells. Because of their versatility, these systems--which combine specific receptor targeting with an imaging agent and drug delivery--are suited to both basic science and applications, from developing therapeutic strategies for autoimmune and alloimmune diseases, to noninvasive tracking of pathogenic T-cell migration.
17563605 Employer benefit design considerations for the era of biotech drugs. 2007 Jun A growing number of employed persons in the United States live and work with potentially complex chronic conditions such as rheumatoid arthritis, multiple sclerosis, and cancer. Increasingly, many of the medications used to treat these serious conditions are costly, primarily because many of the newest drugs are high-cost biotechnology derived pharmaceuticals, referred to in this report as biotech drugs. The rapidly increasing use of new biotech medications for an expanding number of chronic and potentially disabling conditions of working-age adults has significant implications for US employers in the anticipated effect on worker productivity, human capital preservation, and health care costs. However, new approaches, including sophisticated modeling techniques, are providing employers with the insights and guidance necessary to make the benefit design decisions that will provide optimal outcomes to employees while managing employer costs effectively.
17427564 [Case report: tuberculosis of parotid gland]. 2007 Jan Primary tuberculosis of the parotid gland is an unusual clinical presentation. In this report a 32 years old male patient with parotid gland tuberculosis has been presented. The patient has been admitted to Ear, Nose & Throat outpatient clinic of our hospital with the complaint of left facial nodule. Histopathologic examination of the needle aspiration biopsy (NAB) specimen yielded benign necrotic lenfoid tissue, and in cervical ultrasonography cystic formations in left parotid gland were detected. Since the nodule size has increased in the follow-up period, cervical tomography was performed and heterogenous mass in the left side with lobular contour and hypodense appearance in posterior cervical region was detected. Histopathologic examination of the repeated NAB revealed chronic sialadenitis and benign lymphoid hyperplasia, and the patient has undergone left parotidectomy and lymph node dissection. Histopathologic examination of the excisional biopsy specimen revealed necrotising granuloma with diffuse caseification lesions concordant with tuberculosis. The patient was diagnosed as parotid gland tuberculosis, and anti-tuberculous therapy was started with isoniazid, rifampin, ethambutol and pyrazinamide. The history of the patient pointed out that he had used steroid for four months with a suspective diagnosis of rheumatoid arthritis, and his father had tuberculosis. In conclusion, since tuberculosis is a common infection in our country, it should be considered in the differential diagnosis of parotid nodules.
17263820 Sézary syndrome in a patient receiving infliximab for ankylosing spondylitis. 2007 Apr Infliximab, a tumour necrosis factor (TNF)-alpha antagonist, has shown striking efficacy in the treatment of chronic inflammatory rheumatological diseases such as rheumatoid arthritis and ankylosing spondylitis. However, long-term follow-up studies support that treatment with infliximab is associated with an increased risk of non-Hodgkin lymphoma. So far, few cases of cutaneous lymphoma have been reported in patients receiving TNF-alpha-blocking agents. We report a patient who developed Sézary syndrome 17 months after the onset of infliximab therapy for ankylosing spondylitis. Cutaneous lesions partially remitted following infliximab withdrawal and methotrexate treatment. Although the causal link between infliximab and the emergence of Sézary syndrome is uncertain, the present case raises the need for exhaustive long-term registries of malignancies, including primary cutaneous lymphomas, in patients receiving TNF-alpha-blocking agents.
17207896 Neuropeptide Y regulates catecholamine release evoked by interleukin-1beta in mouse chroma 2007 Feb Activation of the hypothalamic-pituitary-adrenal gland (HPA) axis can modulate the immune system. Cytokines and neuropeptide Y (NPY) are potent regulators of the HPA axis and are both produced by the adrenal medulla. The cytokine interleukin-1beta (IL-1beta) belongs to the interleukin-1 family along with interleukin-1alpha and the interleukin receptor antagonist (IL-1ra). The aim of the present study was to determine the interaction between NPY and IL-1beta in catecholamine (norepinephrine, NE and epinephrine, EP) release from mouse chromaffin cells in culture. We found that IL-1beta increased the constitutive release of NPY, NE and EP from mouse chromaffin cells. This IL-1beta stimulatory effect was blocked by IL-1ra. The immunoneutralization of NPY and the use of the NPY Y(1) receptor antagonist (BIBP 3226) inhibited the stimulatory effect of IL-1beta on catecholamine release from these cells. The present work shows that IL-1beta induces catecholamine release, and in turn this peptide will induce an additional increase in catecholamine release acting through the Y(1) receptor. This work suggests that NPY is involved in the regulatory loop between the immune and the adrenal system in some pathophysiological conditions where plasmatic IL-1beta increases, like in sepsis, rheumatoid arthritis, stress or hypertension.
17090024 Activity-based protein profiling reagents for protein arginine deiminase 4 (PAD4): synthes 2006 Nov 15 Protein arginine deiminase 4 (PAD4), which catalyzes the post-translational conversion of peptidyl arginine to peptidyl citrulline, is widely regarded as one of the best new targets for the development of a novel rheumatoid arthritis therapeutic. In addition to its presumed role in this disease, PAD4 is also a calcium-dependent histone deiminase that acts as a transcriptional co-repressor. Herein we describe the design, synthesis, and in vitro evaluation of two fluorescently labeled activity-based protein profiling (ABPP) reagents that specifically and irreversibly modify the active, that is, calcium-bound, form PAD4 with equal affinity to previously described small molecule chemical probes of PAD4 function. These fluorescently tagged ABPPs will be useful for identifying the conditions under which this enzyme is activated in vivo and may prove to be useful RA diagnostics.