Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 21437059 | Long-term use of adalimumab in the treatment of moderate to severe plaque psoriasis: a rev | 2010 Apr 19 | Psoriasis is a chronic T-cell-mediated inflammatory disease that primarily affects the skin and joints. Patients with moderate to severe psoriasis constitute about 30% of the psoriasis population. Treatment of this group is challenging due to the long-term side effects, toxicities and inconvenience of conventional treatments such as phototherapy, methotrexate and cyclosporine. However, recent advances in our understanding of the pathogenesis of psoriasis have led to the popular use of biologics, which offer a safer, more convenient and effective targeted therapy. Adalimumab was originally approved for treating rheumatoid arthritis. Currently, adalimumab is also approved for treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy or when other systemic therapies are medically less appropriate. Since the onset of the use of biologics, there have been concerns over safety and efficacy when used as long-term therapy. This paper reviews all publications, posters and abstracts reporting original data on the efficacy and/or safety of adalimumab in patients treated for chronic plaque psoriasis for more than 1 year. | |
| 19949263 | [Application of FRAX for health check-ups]. | 2009 Dec | WHO's FRAX aims to identify bone-fracture high-risk individuals requiring medical intervention by calculating each individual's 10-year probability (%) of bone fracture based on clinical risk factors or clinical risk factors plus bone mineral density (BMD). The risk factors are age, sex, femoral neck mineral density, or body mass index (BMI) if BMD data are unavailable, history of bone fracture, parental history of femoral neck fracture, smoking, consumption of alcohol, use of steroids, rheumatoid arthritis, and secondary osteoporosis. Model with clinical risk factors alone can predict osteoporotic fracture risk as well as the model with BMD and clinical risk factors. FRAX with clinical risk factors alone would be useful to screen those at high risk of fracture in population-based health check-ups. | |
| 19082529 | Successful treatment of refractory polymyositis with the immunosuppressant mizoribine: cas | 2009 Feb | We describe a patient who presented with polymyositis with anti-Jo-1 antibodies at 18 years after the onset of rheumatoid arthritis and was successfully treated with the immunosuppressive drug mizoribine at the time of exacerbation. She had developed diabetes mellitus, cerebral infarction, and myocardial infarction after high-dose steroid therapy was initiated. Therefore, an immunosuppressant was preferred as the second-line agent. Treatment with 150 mg/day of mizoribine and 8 mg/day of prednisolone resulted in eventual normalization of muscle enzyme levels. Mizoribine is a purine antimetabolite that inhibits T cell activation/proliferation and B cell proliferation. The potential efficacy of mizoribine for polymyositis was suggested by this case. | |
| 19007330 | Translating molecular insights in autoimmunity into effective therapy. | 2009 | Autoimmunity and the pathogenesis of autoimmune diseases were a major focus of the Walter and Eliza Hall Institute, where I started my research career. After my initial studies on immune cell culture and immune regulation, I returned to an analysis of the pathogenesis of human autoimmunity in London. Linking upregulated antigen presentation to autoimmunity led to an investigation of the role of cytokines in rheumatoid arthritis (RA), in collaboration with Ravinder Maini. These experiments defined the concept of a TNF-dependent cytokine cascade driving the manifestations of RA, which led to successful clinical trials of anti-TNF monoclonal antibody in RA patients, heralding a major change in medical practice. This success was made possible by enthusiastic support from many laboratory and clinical colleagues and taught us that cytokines are important rate-limiting steps and hence good therapeutic targets. My current scientific challenge is exploring the hypothesis of whether all major medical needs can be approached via cytokine blockade. | |
| 20686805 | Antibodies against cyclic citrullinated peptides in infectious diseases--a systematic revi | 2010 Dec | Rheumatoid arthritis (RA) is a disease characterized by symmetrical polyarthritis of the large and small joints, and in the majority of patients, there is a presence of the rheumatoid factor and erosions in the X-ray of the joints. More recently, the presence of anti-cyclic citrullinated peptide antibodies (anti-CCP) in this disease has been described, with diagnostic and prognostic value. Nevertheless, these antibodies have also been described in infectious diseases. The aim of the present study was to make a systematic review of the presence of antibodies against citrullinated peptides in infectious diseases. Search was conducted in the MEDLINE (1966 to 2010), Cochrane, SCielo, and LILACS databases, using the terms: "anti-CCP, anti-MCV, and infectious diseases"; "anti-CCP, anti-MCV, and virus"; "anti-CCP, anti-MCV, and mycobacteria"; "anti-CCP, anti-MCV, and tuberculosis"; "anti-CCP, anti-MCV, and leprosy"; "anti-CCP, anti-MCV, and leishmaniasis"; "anti-CCP, anti-MCV, and HIV"; "anti-CCP and HTLV"; "anti-CCP, anti-MCV, and Chagas disease"; "anti-CCP, anti-MCV, and Lyme disease", and the corresponding terms in Portuguese. Twenty-five publications were found, which dealt with anti-CCP and infection, and only one on anti-MCV and infection. Of these, 23 were cross-sectional and three cohort studies. Anti-CCP antibodies were found in various frequencies, reaching 37% in tuberculosis. In the other infections, it was a rare finding. In only one publication, anti-MCV was found in only one patient with hepatitis. Since infectious diseases are capable of running their course with osteoarticular symptoms, sometimes difficult to differentiate from RA, additional studies are necessary to define the performance of the test for the detection of anti-CCP antibodies in populations in which the frequency of such infections is high. | |
| 19585132 | [Biological switches: the 'all-or-none' principle in T-cell activation]. | 2009 Sep | T helper lymphocytes (Th cells) play a central role in cellular defence against pathogens as well as in cellular self tolerance. The activation of Th cells is a crucial process determining the course of a protective immune response. Dysregulated activation processes can lead to pathologic immune reactions and may induce autoimmune diseases. Thus, for example, chronic activation of Th cells can trigger autoimmune diseases such as rheumatoid arthritis. One fundamental feature of antigen-specific T-cell activation is the synthesis of cytokines, e.g. Interleukin- (IL-)2. Here we present results of our working group indicating for the first time that, at the level of the individual cell, IL-2 is expressed in a binary fashion, i.e. according to an all-or-none principle. The identification and characterization of such intracellular switches may provide new options to manipulate the fate of T cells and develop novel therapeutic strategies. | |
| 19568253 | Mesenchymal stem cells: innovative therapeutic tools for rheumatic diseases. | 2009 Jul | Mesenchymal stem cells (MSCs), or multipotent mesenchymal stromal cells as they are also known, have been identified in bone marrow as well as in other tissues of the joint, including adipose, synovium, periosteum, perichondrium, and cartilage. These cells are characterized by their phenotype and their ability to differentiate into three lineages: chondrocytes, osteoblasts and adipocytes. Importantly, MSCs also potently modulate immune responses, exhibit healing capacities, improve angiogenesis and prevent fibrosis. These properties might be explained at least in part by the trophic effects of MSCs through the secretion of a number of cytokines and growth factors. However, the mechanisms involved in the differentiation potential of MSCs, and their immunomodulatory and paracrine properties, are currently being extensively studied. These unique properties of MSCs confer on them the potential to be used for therapeutic applications in rheumatic diseases, including rheumatoid arthritis, osteoarthritis, genetic bone and cartilage disorders as well as bone metastasis. | |
| 19319499 | At crossroads between laboratory disciplines and medical advancements-The Center for Molec | 2009 Apr | The Center for Molecular Medicine (CMM) was conceived and built to respond to the challenges presented by the still common chronic diseases such as atherosclerosis, rheumatoid arthritis, diabetes, allergy, and alcoholism. The Karolinska University Hospital has a proud history of research with developments such as the pacemaker and the gamma-knife. The nearby Karolinska Institutet has a strong presence internationally on the basic sciences. However, the challenges of the "new biology" and the access to the complete human genome, transcriptome, and proteome raised the need for a new research institute that could meet the experimental requirements for translational research. A Foundation was established in 1994 with the goal to build and govern the new enterprise. After an intense fundraising campaign, building could start and CMM (Fig. 1) was inaugurated in 1997. Through more than 10 years of existence, it has evolved into a multidisciplinary research institute with research in four programs, Cardiovascular and Metabolic Diseases, Infection and Immunity, Neuropsychiatric Diseases, and Medical Genetics. Performance parameters have been introduced and scientific impact and relevance are followed annually. Transparency and collaboration between groups (now 28 groups with an approximate total of 400 people engaged in research) and leadership training for junior faculty are means to stimulate "centerness". | |
| 18991025 | Atherosclerosis in autoimmune rheumatic diseases-mechanisms and clinical findings. | 2009 Aug | Atherosclerosis is one of the major entities leading to morbidity and mortality in the western world. It is known now that atherosclerosis cannot be explained merely by the presence of the Framingham traditional risk factors and that autoimmunity takes a significant role in its pathogenesis. It is also known that individuals with autoimmune diseases demonstrate increased incidence of cardiovascular manifestations and subclinical atherosclerotic disease. The mechanisms for the assumed accelerated atherosclerosis in diseases such as systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, and systemic sclerosis include the classical risk factors, but may also be due to chronic inflammatory processes and immune dysregulation. Autoantibodies, autoantigens, pro-inflammatory cytokines, and infectious agents play a role in that process. Involvement of autoimmunity in the pathogenesis of accelerated atherosclerosis in rheumatic diseases and the common pathway that leads to this condition may lead to significant change in prevention of treatment. | |
| 18848375 | Herniation of the temporomandibular joint into the external auditory meatus secondary to b | 2009 Mar | The temporomandibular joint (TMJ) is intimately related to the external auditory meatus (EAM). Herniation of the joint into the EAM occurs secondary to neoplasia, trauma, inflammation and developmental problems [Conover GL, Crammond RJ. Tympanic plate fracture from mandibular trauma. J Oral Maxillofac Surg 1985;43:292-4; Ali TS, Rubinstein JT. Rheumatoid arthritis of the temporomandibular joint with herniation into the external auditory canal. Ann Otol Rhinol Laryngol 2000;109:177-9]. Benign necrotising otitis externa (BNOE) is an uncommon condition characterized by avascular necrosis of the tympanic plate that has been described as a sequela of simple otitis externa. [Wormald PJ. Surgical management of benign necrotizing otitis externa. J Laryngol Otol 1994;108:101-5.] We present a case of BNOE that resulted in a posterior herniation of the TMJ capsule into the EAM. | |
| 21188427 | Upper airway obstruction associated with flexed cervical position after posterior occipito | 2011 Feb | Upper airway obstruction resulting from overflexion fixation of the cervical spine is a rare but life-threatening complication after cervical spine surgery. There are few reports of dyspnea after a posterior cervical fusion. We present the case of a 63-year-old woman with rheumatoid arthritis who developed an upper airway obstruction immediately after an O-C4 fusion. She was reintubated with a fiberoptic scope. Revision surgery allowing the angle to return to the neutral position was performed to ameliorate the overflexion of the cervical spine fixation and the consequent upper airway obstruction. After revision surgery, the upper airway obstruction disappeared. Our experience suggests that intraoperative use of fluoroscopy and extubation with a tube exchanger are recommended to avoid this complication, especially in patients at high risk of upper airway obstruction. | |
| 21157651 | Teriflunomide, an inhibitor of dihydroorotate dehydrogenase for the potential oral treatme | 2010 Nov | Teriflunomide, being developed as a potential oral treatment for multiple sclerosis (MS) by sanofi-aventis, is the active metabolite of the rheumatoid arthritis drug leflunomide. Both teriflunomide and leflunomide are inhibitors of the mitochondrial enzyme dihydroorotate dehydrogenase, which is critically involved in pyrimidine synthesis. The production of activated T-cells largely depends on de novo pyrimidine synthesis, and thus pyrimidine depletion is thought to result in the inhibition of immune cell proliferation. Therapeutic efficacy of teriflunomide has been demonstrated in vivo in an experimental autoimmune encephalomyelitis model of MS using Dark Agouti rats. In a phase II, randomized, double-blind, placebo-controlled clinical trial of patients with relapsing-remitting MS, treatment with teriflunomide reduced the number of active lesions in the brain and preliminary evidence indicated a slowing in the development of disability. Recently reported data from the phase III TEMSO clinical trial support these initial findings. Compared with current therapies, teriflunomide has the advantage of oral administration. Thus, if good efficacy is demonstrated, teriflunomide may have a role to play in the future treatment of MS. | |
| 20941744 | Microparticles in physiological and in pathological conditions. | 2010 Oct | Chronic diseases pose a severe burden to modern National Health Systems. Individuals nowadays have a far more extended lifespan than in the past, but healthy living was only scantily extended. As much as longer life is desirable, it is saddened by chronic diseases and organ malfunctions. One contributor to these problems was recognized to be represented by microparticles (MPs). Our purpose is to better understand MPs, to contrast their ominous threat and possible clinical importance. For this intent we correlated MPs with thrombotic pathologies, hemophilia, malaria, diabetes, cardiovascular diseases, endothelial dysfunctions, pulmonary hypertension, ischemic stroke, pre-eclampsia, rheumatologic diseases-rheumatoid arthritis, polymyositis-dermatomyositis, angiogenesis and tumor progression-cancer; we listed the possibilities of using them to improve transfusion methods, as a marker for acute allograft rejection, in stem cell transplantation, as neuronal biomarkers, to understand gender-specific susceptibility for diseases and to improve vaccination methods and we presented some methods for the detection of MPs. | |
| 20877521 | The Expression of Toll-like Receptors in Dermatological Diseases and the Therapeutic Effec | 2010 Sep | Toll-like receptors are a group of glycoproteins located mostly in cellular membranes, capable of recognizing certain molecules in exogenous microorganisms and initiating immune responses against them through the activation of several intracellular signaling pathways. Toll-like receptors can be stimulated when an inflammatory reaction is needed for the treatment of conditions, such as viral infections or skin cancer, or can be inhibited when a reduction of inflammation is necessary for the treatment of conditions, such as rheumatoid arthritis, systemic lupus erythematosus, and septic shock. In the human skin, keratinocytes and Langerhans cells are known to express these receptors. Skin conditions where Toll-like receptors are known to be upregulated include acne, psoriasis, atopic dermatitis, syphilis, leprosy, Staphylococcus aureus infections, candidiasis, and herpes simplex and varicella zoster infections. Besides imiquimod, which is the most successful and more studied topical Toll-like receptor-modulating agent to date, other topical agents, such as nicotinamide, all-trans retinoic acid, adapalene, zinc, and sodium tosylchloramide, have also been found to exert some of their action through Toll-like receptors. Recent topical agents, including CBT-SL5 and CpG-ODN, are being evaluated for the treatment of inflammatory acne and skin cancer, respectively, and have demonstrated to be effective in the treatment of those conditions. | |
| 20536653 | Sarcoidosis during infliximab therapy for Crohn's disease. | 2010 May | Tumor necrosis factor-alpha (TNF-alpha) antagonists are effective for inflammatory diseases, such as Crohn's disease, rheumatoid arthritis (RA) and psoriasis. Although TNF-alpha antagonists are also useful for sarcoidosis, paradoxical occurrence of sarcoidosis or sarcoidal reaction may be observed. We report a Crohn's disease patient, who developed sarcoidosis during infliximab therapy. A 35-year-old man had been receiving infliximab for 7 months for Crohn's disease. He developed cough and fever, accompanied by an infiltrated erythematous plaque on his right knee. The chest radiography, skin biopsy and laboratory findings were all consistent with sarcoidosis. | |
| 21582293 | N-(2,3-Dimethyl-phen-yl)-4-hydr-oxy-2-methyl-2H-1,2-benzothia-zine-3-carboxamide 1,1-dioxi | 2009 Feb 28 | In the crystal structure of the title compound, C(18)H(18)N(2)O(4)S, the thia-zine ring adopts a distorted half-chair conformation. 1,2-Benzothia-zines of this kind have a wide range of biological activities and are mainly used as medicines in the treatment of inflammation and rheumatoid arthritis. The enolic H atom is involved in an intra-molecular O-H⋯O hydrogen bond, forming a six-membered ring. The mol-ecules arrange themselves into centrosymmetric dimers by means of inter-molecular N-H⋯O hydrogen bonds. A weak inter-molcular C-H⋯O inter-action is also present. | |
| 20556820 | The Fms-like tyrosine kinase 3 ligand, a mediator of B cell survival, is also a marker of | 2010 Nov | OBJECTIVE: To determine if the Fms-like tyrosine kinase 3 ligand (Flt-3L), a cytokine implicated in B cell ontogenesis and proliferation in hematologic malignancies, might be responsible for the increased numbers of circulating Bm2 and Bm2′ B cell subsets in patients with primary Sjögren's syndrome (SS). METHODS: Serum levels of Flt-3L were measured in 64 patients with primary SS and in 20 healthy controls matched for age and sex. Flt-3L and its receptor Flt-3 were quantified in circulating B cells and in salivary gland (SG) biopsy tissues by immunofluorescence analysis. The effect of Flt-3L on circulating B lymphocytes was then determined by coculture with cells of a human SG (HSG) epithelial cell line. RESULTS: Serum levels of Flt-3L were increased in patients with primary SS as compared with controls (mean ± SD 135.8 ± 5.5 versus 64.4 ± 4.5 pg/ml; P < 0.001). Serum levels of Flt-3L in primary SS patients correlated with the numbers of Bm2 and Bm2′ cells (r = 0.46, P < 0.0006), and Flt-3 was selectively expressed in Bm2 and Bm2′ cells. B cell culture experiments showed that Flt-3L potentiated the proliferative effect of anti-IgM stimulation. In SGs, we found that infiltrating B cells expressed Flt-3 and epithelial cells produced Flt-3L. Finally, Flt-3L levels were associated with high disease activity scores and increased risk of developing lymphoma. CONCLUSION: Serum levels of Flt-3L are elevated in patients with primary SS and correlate with abnormal B cell distribution. Flt-3 is mainly expressed by Bm2 and Bm2′ cells. Serum levels of Flt-3L might explain the clinical evolution of primary SS to B cell lymphoma that is observed in some patients, thus opening the possibility of new avenues for therapy. | |
| 19833746 | Expression of proteasomal immunosubunit beta1i is dysregulated in inflammatory infiltrates | 2009 Dec | OBJECTIVE: Minor salivary gland specimens were analyzed to investigate dysregulation of the proteasome system in patients with Sjögren's syndrome (SS) and patients with sicca syndrome. METHODS: Labial biopsy specimens from 17 patients with SS and 11 patients with non-autoimmunesicca syndrome were analyzed by immunohistochemistry for expression of the inducible proteasomal subunits ss1i, ss2i, and ss5i. The infiltrating subsets of lymphocytes were characterized using immunofluorescence stainings against the cell-surface markers CD20 and CD27. Two-dimensional electrophoresis and immunoblotting were used for detection of the proteasomal subunits ss1 and ss1i in peripheral blood monocyte cells. Gene expression of the constitutive subunits ss1, ss2, and ss5 and the corresponding inducible subunits ss1i, ss2i, and ss5i was further investigated at the mRNA level in small lip biopsies using real-time polymerase chain reaction. RESULTS: The expression of ss1i in infiltrating and peripheral immune cells was altered in patients with SS compared to patients with non-autoimmune sicca syndrome and healthy controls. No significant differences were found in ss2i and ss5i expression between the same groups in small lip biopsies. Chisholm-Mason grade and ss1i expression were found to be inversely correlated (Spearman r = -0.461, p = 0.014). The phenotype and distribution of the lymphocytic infiltrate showed no differences between patients with primary and secondary SS regardless of ss1i expression. CONCLUSION: The proteasomal ss1i subunit is dysregulated in peripheral white blood cells and in inflammatory infiltrates of minor salivary glands in patients with SS. | |
| 19605678 | Increased prevalence of antibodies to thyroid peroxidase in dry eyes and mouth syndrome or | 2009 Aug | OBJECTIVE: A subset of patients presenting with sicca features suggestive of primary Sjögren's syndrome (pSS) do not fulfill diagnostic or histopathological criteria. This presentation was previously designated as dry eyes and mouth syndrome (DEMS) or sicca asthenia polyalgia syndrome (SAPS). We sought to define the underlying clinical, laboratory, and histological features of these patients. METHODS: The study population consisted of 27 consecutive patients with DEMS/SAPS; 54 patients with pSS served as controls. Medical charts were retrospectively evaluated for clinical and serological data and frozen sera were tested for the presence of antibodies against HIV, hepatitis C virus, and thyroid antigens. Immunohistochemical analysis of paraffin embedded tissues was also performed. RESULTS: Sicca symptoms and nonspecific musculoskeletal pain were the commonest clinical features of patients with DEMS/SAPS; positive titers of antibodies against thyroid peroxidase was the main underlying abnormality found in 16 out of 27 (59.2%) of patients with DEMS/SAPS compared to 11 out of 54 (20.4%) of pSS controls (p = 0.0009). Histological analysis of the minor salivary gland (MSG) biopsies of patients with DEMS/SAPS disclosed a mild inflammatory infiltration of the interstitial tissue with a predominantly perivascular distribution. CONCLUSION: Patients with DEMS/SAPS present with sicca features and nonspecific musculoskeletal complaints, have high prevalence of antithyroid antibodies, and their MSG biopsies demonstrate a mild interstitial lymphocytic infiltration with a predominantly perivascular distribution. In the setting of clinical practice, we propose that in the presence of DEMS/SAPS testing for antithyroid antibody should be performed. | |
| 18797871 | Diagnostic performance of minor salivary gland biopsy, serological and clinical data in Sj | 2009 Feb | The aim of this study was to investigate the performance of minor salivary gland biopsy (MSGB), serological and clinical data in diagnosis of primary Sjögren's syndrome (pSS). Retrospective review of 216 patients who underwent minor labial salivary gland biopsy in last 5 years was performed. Results of the patients with diagnosis of pSS were compared with the patients failing to fill the classification criteria of pSS. Two groups did not differ significantly in terms of clinical symptoms and signs except presence of Raynaud's phenomenon. Specificity and positive likelihood ratio of clinical signs in diagnosis of pSS were quiet low. A total of 78.7% of pSS patients had a focus score >or=1 (Chiscolm's score III/IV) while all of the non-SS patients had a focus score <1 (P < 0.001). MSGB has the best predictive value with highest sensitivity and specificity for pSS diagnosis. Serological markers have higher predictive values compared to clinical symptoms and signs. Presence of Raynaud's phenomenon, lymphopenia and/or hypergammaglobulinemia strengthens the probability of pSS in a patient with sicca symptoms. |