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ID PMID Title PublicationDate abstract
21243309 Felty's syndrome and Kala-azar: a challenge for the rheumatologist. 2010 Nov Case report of a patient with rheumatoid arthritis who developed severe neutropenia, splenomegaly and was diagnosed with Felty's syndrome. The patient later developed Kala-azar. Both diseases have similar clinical and laboratory presentation, making the differential diagnosis difficult. The present case report aims at drawing attention to the identification of visceral Leishmaniasis infection in patients with rheumatic diseases, as well as possibility of a patient with Kala-azar mimicking a set of symptoms of systemic rheumatic disease.
20554264 [The mastoid osteoma, an incidental feature?]. 2011 Mar Osteoma in the mastoid is a rare benign osteogenic tumour that has been described in literature in only 137 cases. It usually appears in asymptomatic patients, although a few cases are described associated with clinical manifestations. We report three cases of mastoid osteoma: a pedunculated osteoma in the aditus ad antrum (associated with a cholesteatoma), a superficial osteoma of the mastoid surface and a sessile osteoma that progressed to the temporal lobe (associated with vertigo). A brief review of this rare entity is presented and a possible association between mastoid osteoma, cholesteatoma otitis and vertigo is posed.
20490766 Identifying patterns of immune-related disease: use in disease prevention and management. 2010 May BACKGROUND: Childhood susceptibility to diseases linked with immune dysfunction affects over a quarter of the pediatric population in some countries. While this alone is a significant health issue, the actual impact of immune-related diseases extends over a lifetime and involves additional secondary conditions. Some comorbidities are well known (e.g., allergic rhinitis and asthma). However, no systematic approach has been used to identify life-long patterns of immune-based disease where the primary condition arises in childhood. Such information is useful for both disease prevention and treatment approaches. DATA SOURCES: Recent primary research papers as well as review articles were obtained from PubMed, Chem Abstracts, Biosis and from the personal files of the authors. Search words used were: the diseases and conditions shown Figs. 1 and 2 in conjunction with comorbid, comorbidities, pediatric, childhood, adult, immune, immune dysfunction, allergy, autoimmune, inflammatory, infectious, health risks, environment, risk factors. RESULTS: Childhood diseases such as asthma, type-1 diabetes, inflammatory bowel disease, respiratory infections /rhinitis, recurrent otitis media, pediatric celiac, juvenile arthritis and Kawasaki disease are examples of significant childhood health problems where immune dysfunction plays a significant role. Each of these pediatric diseases is associated with increased risk of several secondary conditions, many of which appear only later in life. To illustrate, four prototypes of immune-related disease patterns (i.e., allergy, autoimmunity, inflammation and infectious disease) are shown as tools for: 1) enhanced disease prevention; 2) improved management of immune-based pediatric diseases; and 3) better recognition of underlying pediatric immune dysfunction. CONCLUSIONS: Identification of immune-related disease patterns beginning in childhood provides the framework for examining the underlying immune dysfunctions that can contribute to additional diseases in later life. Many pediatric diseases associated with dysfunctional immune responses have been linked with an elevated risk of other diseases or conditions as the child ages. Diseases within a pattern may be interlinked based on underlying immune dysfunctions and/or current therapeutic approaches for managing the entryway diseases. It may be beneficial to consider treatment options for the earliest presenting diseases that will concomitantly reduce the risk of immune-linked secondary conditions. Additionally, improved disease prevention is possible with more relevant and age-specific immune safety testing.
20117311 Mycobacterial hand infections occurring postoperatively in patients treated with tumor nec 2010 Jan Tumor necrosis factor-alpha inhibitors are potent anti-rheumatic drugs, but there is evidence that the high level of immunosuppression they provide may also lead to a higher risk of infections. At our institution, 3 patients with inflammatory arthritis treated with tumor necrosis factor-alpha inhibitors developed mycobacterial soft tissue infections after routine hand surgery. All 3 patients required multiple surgical procedures, inpatient hospitalizations, and prolonged antibiotic multidrug therapy to clear the infections.
19633800 MonitorNet: the Italian multi-centre observational study aimed at estimating the risk/bene 2009 Apr MonitorNet is a database established by the Italian Society of Rheumatology (SIR) in January 2007 and funded by the Italian Medicines Agency (AIFA), for the active long-term follow-up of patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis treated with biologic agents. All hospital Rheumatology Units in Italy were invited to participate in a non-interventional, observational, epidemiological study. The study is conducted in a routine clinical setting (real-world practice) where biologics are prescribed on the basis of current recommendations. In this report we describe the design, methodology, and present preliminary data of the study. At the time of the analysis (April 2009) the database included 3510 patients: 2469 (70.3%) with established RA, 675 (19.2%) with PsA and 366 (10.4%) with AS. The cumulative follow up period was 8,787 patient-years (RA: 8,388, PsA: 157; AS: 242). There were 1,538 adverse events in 938 (26.7%) patients. Infections were recorded in 630 patients, skin-related adverse events in 142 and post-infusion reactions in 90. A total of 30 malignancies were reported. An interim analysis of efficacy was conducted on 2,148 RA patients. Seven hundred and thirty-one patients (35.8%) achieved EULAR remission (defined as DAS28<2.4). When assessed with the more restrictive CDAI and SDAI criteria, the frequency of remission was lower (17.9% and 14.7% respectively). Availability of funding for this study provided an opportunity to organize a collaborative national network of rheumatology clinics to develop a large multicentre observational study.
19349084 Prevalence and factors associated with urinary tract infections (UTIs) in very old women. 2010 Mar The aim of this study was to describe the prevalence of urinary tract infection (UTI) and associated factors among very old women. In a cross-sectional, population-based study in Sweden and Finland, 532 women were asked to participate and 395 (74.2%) were possible to evaluate for UTI. Data were collected from structured interviews and assessments made during home visits, from medical charts, caregivers and relatives. UTI diagnosis documented in medical records during the preceding 1 and 5 years was registered. About one-third (117/395, 29.6%) were diagnosed as having suffered from at least one UTI in the preceding year and 60% in the preceding 5 years. In a multivariate logistic regression model, UTI in the preceding year, was associated with vertebral fractures (odds ratio (OR) = 3.2; 95% confidence interval (95% CI) = 1.4-7.1), incontinence (OR = 2.8; 95% CI = 1.8-4.5), inflammatory rheumatic disease (OR = 2.8; 95% CI = 1.4-5.7) and multi-infarct dementia (OR = 2.4; 95% CI = 1.3-4.5). UTI is a major public health problem in very old women and were independently associated with vertebral fractures, urinary incontinence, inflammatory rheumatic disease and multi-infarct dementia which might indicate that UTI is not a harmless disease.
19224126 A comparative study of arterial stiffness, flow-mediated vasodilation of the brachial arte 2009 Jun Patients with autoimmune diseases may have increased vascular risk leading to higher mortality rates. Novel imaging techniques are necessary for the early assessment and management of these patients. In this study, we compared augmentation index (AIx) and pulse wave velocity (PWV), indicators of arterial stiffness, to brachial arterial flow-mediated vasodilation (FMD) and common carotid artery intima-media thickness (ccIMT), standard indicators of endothelial dysfunction and atherosclerosis, respectively. We wished to assess the vascular status of autoimmune patients by using a novel, cheap, and reproducible technique, the arteriograph. Altogether, 101 patients with systemic autoimmune diseases including primary antiphospholipid syndrome, systemic sclerosis, rheumatoid arthritis, and polymyositis, all having various types of vasculopathies, as well as 36 healthy individuals were investigated. Arterial stiffness was assessed by a TensioClinic arteriograph, a recently validated technique. Brachial arterial FMD and ccIMT were determined using high-resolution ultrasonography. Autoimmune patients exerted impaired FMD (3.7 +/- 3.8%), increased ccIMT (0.7 +/- 0.2 mm), AIx (1.2 +/- 32.2%), and PWV (9.7 +/- 2.4 m/s) in comparison to control subjects (FMD = 8.4 +/- 4.0%; ccIMT = 0.6 +/- 0.1 mm; Aix = -41.1 +/- 22.5%; PWV = 8.0 +/- 1.5 m/s; p < 0.05). We found a significant negative correlation of FMD with AIx (R = -0.64; p < 0.0001) and PWV (R = -0.37; p = 0.00014). There were significant positive correlations between ccIMT and AIx (R = 0.34; p = 0.0009), ccIMT and PWV (R = 0.44; p < 0.0001), as well as AIx and PWV (R = 0.47; p < 0.0001). AIx, PWV, and ccIMT positively correlated and FMD negatively correlated with the age of the autoimmune patients. Arterial stiffness indicated by increased AIx and PWV may be strongly associated with endothelial dysfunction and overt atherosclerosis in patients with autoimmune diseases. Assessment of arterial stiffness, FMD, and ccIMT are reproducible and reliable noninvasive techniques for the complex assessment of vascular abnormalities in patients at high risk.
21110838 Mapping onto Eq-5 D for patients in poor health. 2010 Nov 26 BACKGROUND: An increasing amount of studies report mapping algorithms which predict EQ-5 D utility values using disease specific non-preference-based measures. Yet many mapping algorithms have been found to systematically overpredict EQ-5 D utility values for patients in poor health. Currently there are no guidelines on how to deal with this problem. This paper is concerned with the question of why overestimation of EQ-5 D utility values occurs for patients in poor health, and explores possible solutions. METHOD: Three existing datasets are used to estimate mapping algorithms and assess existing mapping algorithms from the literature mapping the cancer-specific EORTC-QLQ C-30 and the arthritis-specific Health Assessment Questionnaire (HAQ) onto the EQ-5 D. Separate mapping algorithms are estimated for poor health states. Poor health states are defined using a cut-off point for QLQ-C30 and HAQ, which is determined using association with EQ-5 D values. RESULTS: All mapping algorithms suffer from overprediction of utility values for patients in poor health. The large decrement of reporting 'extreme problems' in the EQ-5 D tariff, few observations with the most severe level in any EQ-5 D dimension and many observations at the least severe level in any EQ-5 D dimension led to a bimodal distribution of EQ-5 D index values, which is related to the overprediction of utility values for patients in poor health. Separate algorithms are here proposed to predict utility values for patients in poor health, where these are selected using cut-off points for HAQ-DI (> 2.0) and QLQ C-30 (< 45 average of QLQ C-30 functioning scales). The QLQ-C30 separate algorithm performed better than existing mapping algorithms for predicting utility values for patients in poor health, but still did not accurately predict mean utility values. A HAQ separate algorithm could not be estimated due to data restrictions. CONCLUSION: Mapping algorithms overpredict utility values for patients in poor health but are used in cost-effectiveness analyses nonetheless. Guidelines can be developed on when the use of a mapping algorithms is inappropriate, for instance through the identification of cut-off points. Cut-off points on a disease specific questionnaire can be identified through association with the causes of overprediction. The cut-off points found in this study represent severely impaired health. Specifying a separate mapping algorithm to predict utility values for individuals in poor health greatly reduces overprediction, but does not fully solve the problem.
19778914 Intranasal administration of recombinant human cartilage glycoprotein-39 as a treatment fo 2010 Sep BACKGROUND: Autoantigen-specific immunotherapy by mucosal tolerance induction via the intranasal route is an attractive therapeutic option for the treatment of autoimmune diseases, including rheumatoid arthritis (RA). Human cartilage glycoprotein-39 (HC gp-39) has been identified as a potential key autoantigen in RA. Based on animal studies, intranasal administration of the autoantigen is hypothesised to induce immunological tolerance in patients with RA and to ameliorate disease activity. In a phase I/IIA clinical trial in patients with RA, intranasal application of HC gp-39 was safe and well tolerated. OBJECTIVE: To investigate the efficacy of intranasally administered fully human, recombinant HC gp-39 (Org 39141) by a large clinical study. METHODS: In a 13-week multicentre, double-blind, randomised, placebo-controlled, parallel-group, dose-finding, proof-of-concept trial, patients with RA (disease-modifying antirheumatic drug (DMARD) naive or after washout of DMARD treatment) were randomised to receive either intranasal applications of placebo or HC gp-39 in doses of 30, 150, 300 or 600 microg, once a week. The primary efficacy variable was the 28 joint count Disease Activity Score (DAS28). RESULTS: During the treatment period the DAS28 decreased similarly for all treatment groups-including placebo-indicating lack of efficacy of intranasal HC gp-39 treatment in the current setting. Safety variables were similar for all study groups. CONCLUSION: It was concluded that with the treatment protocol used (dose levels and frequency of dosing), intranasal treatment with Org 39141 was safe but did not result in more clinical improvement than in placebo-treated patients.
21161534 Causes of DMARD withdrawal following ADR within 6 months of initiation among Indian rheuma 2012 Mar The present study was conducted in Indian rheumatoid arthritis (RA) patients prescribed disease-modifying anti-rheumatic drugs (DMARDs) to determine the incidence and type of adverse drug reactions (ADRs) leading to their withdrawal in the initial 6 months of therapy. This was considered important as pharmacogenetic variations in the pattern of RA in different populations and genetic differences in efficacy and safety to drugs demand separate studies to be conducted in different populations. Hospital records were used to identify 1,000 consecutive patients with RA fulfilling the American College of Rheumatology criteria and having at least 6-month follow-up. Age, gender, duration of arthritis, drug usage and ADR-related drug withdrawal were recorded from the charts. Most of the patients were put on single DMARD. Combined use of DMARD was less frequent and non-use of DMARD was common; however, disease control was good. The commonest DMARD used in our hospital was hydroxychloroquine 444 (44%) and the commonest combination used was methotrexate with hydroxychloroquine by 55 (6%). Sulphasalazine use showed preference to young and males. Supportive drugs used were NSAIDs by 883 (88%), corticosteroids by 646 (65%), paracetamol by 594 (59%) and amitriptyline by 88 (9%). Incidence of ADR-related DMARD withdrawal was maximum with leflunomide 2/15 (13.33%) followed by methotrexate 9/116 (7.76%), sulphasalazine 6/185 (3.24%), chloroquine 3/131 (2.29%) and hydroxychloroquine 8/444 (1.8%). Severity and symptomatology of disease, genetic pattern of patients, financial status, previous experience of the clinicians and patients, availability of drugs, patient expectations and compliance were the main factors that lead to a difference in pattern of therapy in our patients compared to other population.
18678578 Local delivery of a recombinant adenoassociated vector containing a tumour necrosis factor 2009 Aug OBJECTIVE: To examine the safety and tolerability of a single intra-articular injection of rAAV2-TNFR:Fc, an adenoassociated virus serotype 2 vector containing the cDNA for the human tumour necrosis factor-immunoglobulin Fc fusion gene (tgAAC94), in subjects with inflammatory arthritis. METHODS: In a double-blind, placebo-controlled, phase 1, dose-escalation study, 15 subjects with inflammatory arthritis (14 with rheumatoid arthritis and 1 with ankylosing spondylitis) not receiving tumour necrosis factor alpha (TNFalpha) inhibitors with persistent moderate (grade 2) or severe (grade 3) swelling in a target joint due to inflammatory arthritis received a single intra-articular injection of rAAV2-TNFR:Fc at 1 x 10(10) (n = 5) or 1 x 10(11) (n = 6) DNase resistant particles per ml joint volume or placebo (n = 4) into a knee (n = 14) or ankle (n = 1). Safety was assessed through adverse event monitoring. As a secondary objective, changes in injected joint tenderness and swelling scores, each measured on a four-point scale, were evaluated. RESULTS: Intra-articular injections of rAAV2-TNFR:Fc were well tolerated with no major safety issues. One event, mild knee pruritus, was considered probably related. Synovial fluid TNFR:Fc protein was not detected (nor expected) at the doses used. At 12 weeks after injection, a two-point decrease in swelling was noted in 2/11 and 2/4 subjects injected with rAAV2-TNFR:Fc and placebo, respectively. CONCLUSION: A single dose of intra-articular rAAV2-TNFR:Fc appears to be safe and well tolerated in subjects without concurrent systemic TNFalpha antagonist use. It is thus feasible to proceed with larger trials to further test the safety and efficacy of local TNFR:Fc gene transfer as a therapeutic modality for patients with inflammatory arthritis.
19421051 Evaluation of patients with dry eye for presence of underlying Sjögren syndrome. 2009 Jun PURPOSE: To evaluate the rate of Sjögren syndrome (SS) in a cohort of patients with dry eye syndrome. METHODS: Medical records of patients with a primary diagnosis of dry eye syndrome (International Classification of Diseases [ICD] code 375.15 or 370.33) were reviewed retrospectively. Patients who had 2 or more visits to a single dry eye center during a 2-year period (January 2004 to January 2006) were considered. RESULTS: Two hundred twenty patients with dry eye syndrome were identified. A total of 57 patients (25.9%) had an underlying rheumatic condition: 25 patients (11.4%) had rheumatoid arthritis and 24 (10.9%) had primary Sjögren syndrome (PSS). Majority of the patients with rheumatoid arthritis (96%) carried the diagnosis at the time of presentation. Of all patients with PSS, only 33.3% (8/24) carried the diagnosis at the time of presentation. Fifty percent (12/24) were diagnosed as a result of the initial evaluation. Among those, only 66.6% (8/12) tested SSA (anti-Ro antibodies) or SSB (anti-La antibodies) positive. One third of patients (4/12) tested only antinuclear antibody positive at a titer of <1/320 and required minor salivary gland biopsy for definitive diagnosis. Additional 16.7% (4/24), who were initially serologically negative, eventually underwent minor salivary gland biopsy and became diagnosed with SS. CONCLUSIONS: PSS seems to be underdiagnosed in patients with dry eye syndrome and should be the focus of diagnostic evaluations. A minor salivary gland biopsy might be required for a definitive diagnosis in a significant proportion of the patients with SS.
18635595 Dissecting the contribution of innate and antigen-specific pathways to the breach of self- 2009 Jun BACKGROUND: The relative roles of innate immunity and antigen-specific T cells in rheumatoid arthritis remain controversial. Previous studies demonstrated that T-helper type 1 cells of irrelevant antigen specificity (ovalbumin) induced a transient arthritis in BALB/c mice, which recapitulates many of the pre-articular and articular features of human disease and is associated with the emergence of autoreactive T and B-cell responses to joint-specific antigens. However, the mechanisms underlying this phenomenon were unclear. OBJECTIVES: The aim of this study was to dissect the relative contribution of innate and heterologous antigen-specific pathways to the breach of self-tolerance and pathology observed in this model and how this may result from modified T and B-cell interactions. METHODS: To address this issue, experimental arthritis was elicited either by a non-specific inflammatory stimulus alone, by activation of T cells of an irrelevant specificity or a combination of both. RESULTS: The non-specific inflammatory response generated by lipopolysaccharide led to articular inflammation and cartilage erosion, but did not break tolerance to joint-specific antigens. In contrast, local activation of T cells of an irrelevant specificity produced a similar pathological picture but, in addition, induced T-cell responses to unrelated joint-specific antigens with associated activation of autoreactive B cells. These effects could be further potentiated by the addition of lipopolysaccharide. CONCLUSION: These data demonstrate that non-specific inflammation alone is insufficient to breach self-tolerance. In contrast, T cells of an irrelevant specificity, when triggered locally in an antigen-specific manner, can breach self-tolerance leading to arthritis and autoantibody production, which can then be amplified in a non-specific manner.
19495767 Spontaneous displacement of olecranon fracture through geode salvaged by elbow replacement 2010 Apr We present a case of pathological fracture of olecranon through a giant geode. Fracture was initially undisplaced and was treated conservatively. It later progressed to a transolecranon dislocation as a result of a pseudarthrosis at the fracture site. The patient presented 4 years later when she developed symptoms of ulnar nerve palsy. She was treated by a total elbow arthroplasty with ulnar nerve transposition. The current report highlights this unusual case and reviews the relevant literature.
20506062 Ruxolitinib, a selective JAK1 and JAK2 inhibitor for the treatment of myeloproliferative n 2010 Jun Ruxolitinib (INCB-018424) is a potent, orally available, selective inhibitor of both JAK1 and JAK2 of the JAK-STAT signaling pathway, being developed by Incyte Corp and Novartis AG. Ruxolitinib was initially developed to target the constitutive activation of the JAK-STAT pathway in patients with myeloproliferative neoplasms (MPNs). Meaningful reductions in spleen size and constitutional symptoms have been noted in patients with myelofibrosis (both primary and post-essential thrombocythemia/polycythemia vera). Data from a phase I/II clinical trial led to ongoing registration trials in the US and Europe. Toxicity (primarily decreased erythropoiesis and thrombocytopoiesis) has been managed by close control of dosing. The inhibition of inflammatory cytokine signaling through JAK1 inhibition has led to intriguing results in patients with rheumatoid arthritis and psoriasis (using a topical cream formulation). Ruxolitinib is a well tolerated, first-in-class JAK2 inhibitor with various potential clinical indications.
20035675 [Recombinant proteins or monoclonal antibodies: comparative properties and interest in rhe 2009 Dec Therapeutics options for inflammatory diseases, such as rheumatoid arthritis (RA), have increased tremendously in the past decade with the introduction of biologic therapies, such as monoclonal antibodies or recombinant fusion proteins. These have proven to be highly successful in treating inflammatory or autoimmune diseases, by blocking certain key molecules involved in the pathogenesis of the illness, cytokines (TNF) or immune coactivators (CTLA-4). Thus in rheumatoid arthritis, TNF can be neutralized both by monoclonal antibodies (adalimumab, infliximab) or recombinant inhibitors such as etanercept or CTLA-4 Ig abatacept. All have been marketed and proven to be highly effective in the treatment of RA, and we will discuss parameters which are taken into account to select monoclonal antibody or recombinant inhibitors. These include drug-related (target affinity, pharmacokinetics, mechanisms of action, etc.) and patient - (efficacy and side effects) or disease-related characteristics. Their impact on current clinical practice and future trends are discussed.
18846409 Isolated polyethylene exchange versus acetabular revision for polyethylene wear. 2009 Jan Polyethylene wear and osteolysis are not uncommon in THA mid- and long-term. In asymptomatic patients the dilemma faced by the orthopaedic surgeon is whether to revise the cup and risk damage to the supporting columns and even pelvic discontinuity or to perform isolated polyethylene exchange and risk a high rate of postoperative recurrent instability and dislocation that will necessitate further surgery. We retrospectively reviewed 62 patients (67 hips) who underwent revision arthroplasty for polywear and osteolysis. Thirty-six hips had isolated polyethylene exchange, while 31 had full acetabular revision. The minimum followup was 2 years (mean, 2.8 years; range, 2-5 years). Three of 36 hips with a retained cup grafted through the cup holes failed within 5 years due to acetabular loosening. One of 31 hips with full revision underwent re-revision for aseptic cup loosening at 5 months postoperatively. Although we do not recommend prophylactic revision of all cups for polywear and osteolysis, the patient may be warned of the possibility of an approximate 10% failure rate when retaining the acetabular component. We do, however, advocate cup extraction in the following situations: damage to the locking mechanism, erosion of the femoral head through the liner and into the cup damaging the metal, and a malpositioned component that may jeopardize the stability of the revision. LEVEL OF EVIDENCE: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
19066890 Total knee replacement in the fixed valgus deformity using a lateral approach: role of the 2009 Dec The purpose of this work was to document eleven years of experience in knee replacement for fixed knee valgus through a lateral approach with special emphasis on the balancing procedures. At a mean follow-up of seven years, only one revision for sepsis was required in this series of 63 knee replacements. The mean knee score improved from 37 (range 20-45) to 91 (range 65-100) at the last review (p < 0.01) while the function score increased from 29.5 (range 0-50) to 78.7 (range 10-100) (p = 0.01). The mean mechanical axis (HKA) was 14.7 degrees of valgus preoperatively and 1 degrees of valgus postoperatively. After the iliotibial band was automatically released in the approach, only four of 63 knees required additional release for tightness in extension. These results underline the appeal of the lateral approach with the automatic release of the iliotibial band. If required, additional ligament release is recommended step-by-step after bone section to avoid postoperative instability.
20518843 Association of SUMO4 M55V polymorphism with susceptibility to autoimmune and inflammatory 2010 Oct The purpose of this study was to generate large-scale evidence on whether SUMO4 M55V polymorphism is associated with autoimmune and inflammatory diseases using a meta-analysis. We surveyed studies on the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases in PubMed. Meta-analysis was performed for genotypes AG versus AA, GG versus AA, GG versus AA + AG, AG + GG versus AA and G allele versus A allele in a fixed/random effect model. We identified 16 studies (11, 407 cases and 10, 679 controls) using PubMed search. When all groups were pooled, we detected the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases (G versus A: OR = 1.11, 95%CI = 1.03-1.19, P = 0.005; AG +GG versus AA: OR=1.17, 95%CI=1.06-1.28, P=0.001; GG versus AA+AG: OR=1.07, 95%CI=0.94-1.21, P=0.29; GG versus AA: OR=1.15, 95%CI=1.00-1.34, P=0.06; AG versus AA: OR=1.15, 95%CI=1.08-1.23, P<0.0001). In subgroup analyses, we detected the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases in Asian population (G versus A: OR=1.18, 95%CI=1.08-1.28, P=0.0001; AG+GG versus AA: OR=1.30, 95%CI=1.16-1.45, P<0.00001; GG versus AA+AG: OR=1.04, 95%CI=0.78-1.37, P=0.80; GG versus AA: OR=1.20, 95%CI=0.99-1.45, P=0.07; AG versus AA: OR=1.32, 95%CI=1.18-1.49, P<0.00001). But the association was not found in Caucasian population. Meanwhile, an association of SUMO4 M55V polymorphism with autoimmune diabetes was found (G versus A: OR=1.18, 95%CI=1.08-1.30, P=0.0005; AG+GG versus AA: OR=1.22, 95%CI=1.13-1.32, P<0.00001; GG versus AA+AG: OR=1.15, 95%CI=0.96-1.38, P=0.13; GG versus AA: OR=1.32, 95%CI=1.08-1.60, P=0.006; AG versus AA: OR=1.23, 95%CI=1.13-1.33, P<0.00001). This meta-analysis demonstrates the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases, especially in Asian population.
19680656 Epidermal growth factor increases prostaglandin E2 production via ERK1/2 MAPK and NF-kappa 2010 Feb High concentration of epidermal growth factor (EGF) is found in the synovial fluid of rheumatoid arthritis (RA) that might imply the involvement of EGF in the pathogenesis of arthritic diseases. In order to investigate if EGF is involved in the regulation of cyclooxygenase-2 (COX-2) and the prostaglandin E(2) (PGE(2)) production in fibroblast like synoviocytes (FLS) from patients with RA. The levels of COX-2 and microsomal prostaglandin E synthase-1 (mPGES-1) were evaluated using RT-PCR and Western blot analysis. Electrophoretic mobility shift assay (EMSA) was performed to investigate EGF mediated DNA binding activity of nuclear factor-kappaB (NF-kappaB). PGE(2) levels were analyzed by ELISA. EGF enhanced both COX-2 protein and mRNA expressions. mPGES-1 mRNA level was also increased by EGF treatment. EGF also stimulated ERK1/2 MAPK activity and the inhibition of ERK1/2 by PD098059 (ERK1/2 specific inhibitor) resulted in the suppression of EGF-induced COX-2 expression. The DNA binding activity of NF-kappaB was remarkably increased by EGF treatment and the pretreatment of PD098059 abolished EGF-stimulated NF-kappaB activity. We also observed that the level of PGE(2) was significantly elevated with the treatment of EGF in FLS, and the pretreatment of PD098059 abolished this stimulating effect. These results suggest that EGF is involved in the inflammatory process of RA by stimulating COX-2 expression and PGE(2) production. And EGF enhanced PGE(2) production appears to be mediated via ERK1/2 MAPK and NF-kappaB pathway in FLS.