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ID PMID Title PublicationDate abstract
18466483 Modeling of PTPN22 and HLA-DRB1 susceptibility to rheumatoid arthritis. 2007 In the present paper, we used the North American Rheumatoid Arthritis Consortium data provided for Genetic Analysis Workshop 15 Problem 2 to: 1) estimate the penetrances of PTPN22 and HLA-DRB1 and, 2) test the selected model of PTPN22 conditional on the rheumatoid factor status. To achieve these aims, we used the marker association segregation chi-square method, fitting simultaneously both genotype frequency and identical by descent distributions in a sample of 3690 White individuals from 604 nuclear families. A co-dominant model fitted the rs2476601 (R620W) single-nucleotide polymorphism (SNP) of the PTPN22 gene well, whereas a lack of fit for all models was observed for the HLA-DRB1 locus. Testing genetic models of rheumatoid arthritis that include the PTPN22 SNP in addition to the HLA-DRB1 locus did not affect the results, nor did subgroup analysis of PTPN22 conditional on the rheumatoid factor status. In conclusion, PTPN22 R620W SNP is a risk factor for rheumatoid arthritis. The genetic architecture of the HLA-DRB1 locus is highly complex, and more elaborate modeling of this locus is required.
18466440 Large-scale linkage analysis of 1302 affected relative pairs with rheumatoid arthritis. 2007 Rheumatoid arthritis is the most common systematic autoimmune disease and its etiology is believed to have both strong genetic and environmental components. We demonstrate the utility of including genetic and clinical phenotypes as covariates within a linkage analysis framework to search for rheumatoid arthritis susceptibility loci. The raw genotypes of 1302 affected relative pairs were combined from four large family-based samples (North American Rheumatoid Arthritis Consortium, United Kingdom, European Consortium on Rheumatoid Arthritis Families, and Canada). The familiality of the clinical phenotypes was assessed. The affected relative pairs were subjected to autosomal multipoint affected relative-pair linkage analysis. Covariates were included in the linkage analysis to take account of heterogeneity within the sample. Evidence of familiality was observed with age at onset (p << 0.001) and rheumatoid factor (RF) IgM (p << 0.001), but not definite erosions (p = 0.21). Genome-wide significant evidence for linkage was observed on chromosome 6. Genome-wide suggestive evidence for linkage was observed on chromosomes 13 and 20 when conditioning on age at onset, chromosome 15 conditional on gender, and chromosome 19 conditional on RF IgM after allowing for multiple testing of covariates.
17228221 Review of medications used in juvenile rheumatoid arthritis. 2007 Jan Juvenile rheumatoid arthritis is a chronic condition. The goal of therapy is to control pain, preserve joint range of motion and function, minimize systemic complications, and assist in normal growth and development. Recent advances in understanding the pathophysiology of arthritis have expanded the treatment of this chronic condition. Many medications including nonsteroidal anti-inflammatory agents, disease-modifying antirheumatic drugs, biologic agents, and cytotoxic agents are available for treating juvenile rheumatoid arthritis. Emergency medicine physicians should be familiar with the different classes and adverse effects of these drugs.
16651348 Ophthalmologic examinations in children with juvenile rheumatoid arthritis. 2006 May Unlike the joints, ocular involvement with juvenile rheumatoid arthritis is most often asymptomatic; yet, the inflammation can cause serious morbidity with loss of vision. Scheduled slit-lamp examinations by an ophthalmologist at specific intervals can detect ocular disease early, and prompt treatment can prevent vision loss.
20477056 Autoantibody production in patients treated with anti-TNF-alpha. 2008 Mar Patients with rheumatoid arthritis, Crohn's disease or spondyloarthritis who are treated with selective TNF-alpha inhibitors may develop autoantibodies, such as antinuclear antibodies (ANAs) and anti-dsDNA antibodies. Various methods have shown that infliximab led to ANAs in 29-76.7% and anti-dsDNA antibodies in 10-29% of rheumatoid arthritis patients participating in clinical trials. Furthermore, ANAs and anti-dsDNA antibodies have appeared in 11-36 and 5-15% of rheumatoid arthritis patients treated with etanercept and 12.9% and 5.3% of those treated with adalimumab, respectively. Antiphospholipid antibodies, which are mainly detected by means of anticardiolipin assays, have also been found in rheumatoid arthritis patients receiving TNF-alpha blockers. There have been a number of reports of the development of antidrug antibodies, of which those against infliximab lead to infusion reactions and shorter responses to treatment. This has led some authors to conclude that it is necessary to add methotrexate to infliximab in order to reduce the risk of the appearance of anti-idiotype autoantibodies.
17870671 Clinical and serological features of patients with autoantibodies to GW/P bodies. 2007 Dec GW bodies (GWBs) are unique cytoplasmic structures involved in messenger RNA (mRNA) processing and RNA interference (RNAi). GWBs contain mRNA, components of the RNA-induced silencing complex (RISC), microRNA (miRNA), Argonaute proteins, the Ge-1/Hedls protein and other enzymes involving mRNA degradation. The objective of this study was to identify the target GWB autoantigens reactive with 55 sera from patients with anti-GWB autoantibodies and to identify clinical features associated with these antibodies. Analysis by addressable laser bead immunoassay (ALBIA) and immunoprecipitation of recombinant proteins indicated that autoantibodies in this cohort of anti-GWB sera were directed against Ge-1/Hedls (58%), GW182 (40%) and Ago2 (16%). GWB autoantibodies targeted epitopes that included the N-terminus of Ago2 and the nuclear localization signal (NLS) containing region of Ge-1/Hedls. Clinical data were available on 42 patients of which 39 were female and the mean age was 61 years. The most common clinical presentations were neurological symptoms (i.e. ataxia, motor and sensory neuropathy) (33%), Sjögren's syndrome (SjS) (31%) and the remainder had a variety of other diagnoses that included systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and primary biliary cirrhosis (PBC). Moreover, 44% of patients with anti-GWB antibodies had reactivity to Ro52. These studies indicate that Ge-1 is a common target of anti-GWB sera and the majority of patients in a GWB cohort had SjS and neurological disease.
19662201 The Clinical Application of Anti-CCP in Rheumatoid Arthritis and Other Rheumatic Diseases. 2007 May 3 Rheumatoid arthritis (RA) is a common rheumatic disease in Caucasians and in other ethnic groups. Diagnosis is mainly based on clinical features. Before 1998, the only serological laboratory test that could contribute to the diagnosis was that for rheumatoid factor (RF). The disease activity markers for the evaluation of clinical symptoms or treatment outcome were the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). As a matter of fact, the diagnosis of early RA is quite impossible, as the clinical criteria are insufficient at the beginning stage of the disease. In 1998, Schelleken reported that a high percentage of RA patients had a specific antibody that could interact with a synthetic peptide which contained the amino acid citrulline. The high specificity (98%) for RA of this new serological marker, anti-cyclic citrullinated antibody (anti-CCP antibody), can be detected early in RA, before the typical clinical features appear. The presence or absence of this antibody can easily distinguish other rheumatic diseases from RA. Additionally, the titer of anti-CCP can be used to predict the prognosis and treatment outcome after DMARDs or biological therapy. Therefore, with improvement of sensitivity, the anti-CCP antibody will be widely used as a routine laboratory test in the clinical practice for RA.
27741728 Nice limits treatment choice for rheumatoid arthritis(NICE is being accused of taking away 2008 Oct 13 The National Institute for Health and Clinical Excellence (NICE) has issued another unpopulardecision, this time for rheumatoid arthritis (RA) patients. In mid-July the organisation ruled that patients taking one tumour necrosis factor TNF-α inhibitor cannot switch to another, as is currently the practice. The decision has bewildered clinicians and angered patients, and both groups have criticised the judgement, saying it will leave patients in needless pain and with restricted mobility.
16821267 Comparative analysis of autoantibodies against a-fodrin in serum, tear fluid, and saliva f 2006 Jul OBJECTIVE: To evaluate levels of IgA and IgG antibodies against a-fodrin in serum, tear fluid, and saliva and compare them with anti-Ro and anti-La antibody levels in the same samples of patients with Sjögren's syndrome (SS). METHODS: Samples from 25 patients with SS (17 primary and 8 secondary), 8 patients with systemic lupus erythematosus (SLE), and 7 patients with rheumatoid arthritis (RA) as well as 20 healthy blood donor controls were collected. Antibodies were measured using ELISA. RESULTS: Although 40% of patients with primary SS had IgG anti-a-fodrin in their sera, it was also found in 36% and 32% of samples of their tear fluid and saliva, respectively. IgA a-fodrin antibodies were detected in 32% of SS sera, 20% of tear fluid samples, and 32% of saliva samples. Although the level of IgG anti-a-fodrin was significantly greater in serum, tear fluid, and saliva of SS patients compared to controls (p < 0.001), a significant difference was observed only in serum and saliva. While anti-Ro was detected in 48%, 56%, and 24% of serum, tear fluid, and saliva samples, respectively, anti-La was found in 40%, 44%, and 28%. Significant association was observed between serum IgG antibodies against a-fodrin and dry eye symptom score and rose bengal staining score. A negative association was also noted between tear IgA antibodies against a-fodrin and Schirmer I test. CONCLUSION: Correlation of IgG and IgA antibodies against a-fodrin with the severity of eye involvement suggests that these autoantibodies may be considered activation markers of SS.
18392103 Indian herbal medicines: possible potent therapeutic agents for rheumatoid arthritis. 2007 Jul Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology and is mainly characterized by the progressive erosion of cartilage leading to chronic polyarthritis and joint distortion. Although the exact pathogenesis of the disease has yet not been elucidated, however, studies suggest that cellular proliferation of synoviocytes result in pannus formation which damages the cartilage and bone. Recent reports also support the role of free radicals in its pathogenesis. Apart from the conventional treatment strategies using nonsteroidal anti-inflammatory drugs, disease modifying antirheumatic drugs and glucocorticoids, newer and safer drugs are continuously being searched, as long term usage of these drugs have resulted in adverse effects. Alternative medicine provides another approach for treatment of RA and currently a number of medicinal plants are under scientific evaluation to develop a novel drug. There is a dire need to investigate the complete therapeutic potential and adverse effects, if any, of these herbals for providing newer and safer treatment options with minimum side effects. In this review we have tried to explore various Indian ancient Ayurvedic, Unani and Tibbi, as also some Chinese and Korean, herbals for their potential to treat RA.
25610023 A coincidence of rheumatoid arthritis, autoimmune thyroid disease and vitiligo in a single 2008 Apr It has been widely observed that disorders with an autoimmune pathogenesis occur with increased frequency in patients with a history of another autoimmune disease (AD). The numbers of documented cases of a co-occurrence of different autoimmune diseases in a single patient in addition to studies investigating the possible common etiopathogenesis of these diseases have increased in recent years. Available data suggest that the presence of one AD should alert the clinician to the possibility of a second AD. In this report, we aimed to draw attention to these potential coincidences and the possible pathogenetic linkages between three distinct ADs in a single individual diagnosed with rheumatoid arthritis, autoimmune thyroid disease and vitiligo. Further documentation of observations of possible coincidence are required in order to yield results that may shed light on the biological pathways of these diseases.
19506728 Gene polymorphisms and pharmacogenetics in rheumatoid arthritis. 2008 Sep Rheumatoid arthritis (RA) is a systemic, chronic and inflammatory disease of unknown etiology with genetic predisposition. The advent of new biological agents, as well as the more traditional disease-modifying antirheumatic drugs, has resulted in highly efficient therapies for reducing the symptoms and signs of RA; however, not all patients show the same level of response in disease progression to these therapies. These variations suggest that RA patients may have different genetic regulatory mechanisms. The extensive polymorphisms revealed in non-coding gene-regulatory regions in the immune system, as well as genetic variations in drug-metabolizing enzymes, suggest that this type of variation is of functional and evolutionary importance and may provide clues for developing new therapeutic strategies. Pharmacogenetics is a rapidly advancing area of research that holds the promise that therapies will soon be tailored to an individual patient's genetic profile.
20477107 Citrullinated collagens in the pathogenesis of rheumatoid arthritis. 2007 Mar Citrulline formation through the deimination of arginine residues has recently been identified as an enzymatic post-translational modification of proteins that could be related to breaking the tolerance to self-antigens in the development of rheumatoid arthritis. Autoantibodies recognizing citrullinated peptides are highly specific indicators of early rheumatoid arthritis. However, current knowledge of the natural proteins that are citrullinated does not explain the main manifestations of the disease, that is, progressive damage to cartilage and bone - tissues rich in extracellular matrix. Several collagen types are present in the joint, where they provide the structural scaffold of the tissues. Recent findings indicate that both the ubiquitous Type I collagen and the cartilage-specific Type II collagen can be enzymatically citrullinated in vitro. Synthetic citrullinated peptides related to collagen sequences can be used as antigens. Autoantibodies to these citrullinated forms are found in patients with early rheumatoid arthritis. This review summarizes what is known regarding the occurrence of citrulline in a major class of extracellular matrix proteins, the fibrillar collagens and the significance of autoantibodies to citrulline in these proteins.
20476948 Methotrexate in rheumatoid arthritis. 2007 Jan After half a century of use, methotrexate continues to be a cornerstone in the therapy of rheumatoid arthritis. Renewed interest in the 1980s has brought new insights into the mechanisms of action and safety of the drug. The use of combination therapy in rheumatoid arthritis has not masked the value of methotrexate in a competitive market in any way. We review the pharmacodynamics and pharmacokinetics as applicable to its clinical use as an anti-inflammatory and disease-modifying agent here.
19707357 Biological therapies for the treatment of juvenile idiopathic arthritis: Lessons from the 2008 Jun Biologics have advanced the therapy of adult and pediatric arthritis. They have been linked to rare serious adverse outcomes, but the actual risk of these events is controversial in adults, and largely unknown in pediatrics. Because of the paucity of safety and efficacy data in children, pediatric rheumatologists often rely on the adult literature. Herein, we reviewed the adult and pediatric literature on five classes of medicines: Tumor necrosis factor (TNF) inhibitors, anakinra, rituximab, abatacept, and tocilizumab. For efficacy, we reviewed randomized controlled studies in adults, but did include lesser qualities of evidence for pediatrics. For safety, we utilized prospective and retrospective studies, rarely including reports from other inflammatory conditions. The review included studies on rheumatoid arthritis and spondyloarthritis, as well as juvenile idiopathic arthritis. Overall, we found that the TNF inhibitors have generally been found safe and effective in adult and pediatric use, although risks of infections and other adverse events are discussed. Anakinra, rituximab, abatacept, and tocilizumab have also shown positive results in adult trials, but there is minimal pediatric data published with the exception of small studies involving the subgroup of children with systemic onset juvenile idiopathic arthritis, in whom anakinra and tocilizumab may be effective therapies.
18466527 Data for Genetic Analysis Workshop (GAW) 15 Problem 2, genetic causes of rheumatoid arthri 2007 For Genetic Analysis Workshop 15 Problem 2, we organized data from several ongoing studies designed to identify genetic and environmental risk factors for rheumatoid arthritis. Data were derived from the North American Rheumatoid Arthritis Consortium (NARAC), collaboration among Canadian researchers, the European Consortium on Rheumatoid Arthritis Families (ECRAF), and investigators from Manchester, England. All groups used a common standard for defining rheumatoid arthritis, but NARAC also further selected for a more severe phenotype in the probands. Genotyping and family structures for microsatellite-based linkage analysis were provided from all centers. In addition, all centers but ECRAF have genotyped families for linkage analysis using SNPs and these data were additionally provided. NARAC also had additional data from a dense genotyping analysis of a region of chromosome 18 and results from candidate gene studies, which were provided. Finally, smoking influences risk for rheumatoid arthritis, and data were provided from the NARAC study on this behavior as well as some additional phenotypes measuring severity. Several questions could be evaluated using the data that were provided. These include comparing linkage analysis using single-nucleotide polymorphisms versus microsatellites and identifying credible regions of linkage outside the HLA region on chromosome 6p13, which has been extensively documented; evaluating the joint effects of smoking with genetic factors; and identifying more homogenous subsets of families for whom genetic susceptibility might be stronger, so that linkage and association studies may be more efficiently conducted.
18438907 Safety and usefulness of minor salivary gland biopsy: retrospective analysis of 502 proced 2008 May 15 OBJECTIVE: To analyze the safety of our biopsy technique and the effectiveness of minor salivary gland biopsy (MSGB) for the diagnosis of Sjögren's syndrome (SS) and amyloidosis. METHODS: We conducted a retrospective analysis of 452 patients with suspected SS and 50 with suspected amyloidosis and negative periumbilical fat aspiration analysis who underwent MSGB at a single center. Diagnostic evaluation for SS included Schirmer's test, unstimulated whole salivary flow, detection of antinuclear antibodies and anti-SSA/SSB, erythrocyte sedimentation rate, C-reactive protein, IgM rheumatoid factor, and serology for hepatitis C virus. For all biopsy samples, a cumulative focus score on multilevel sections was calculated. SS was diagnosed according to American-European Consensus Group (AECG) criteria. Histologic evaluation for amyloidosis was performed using Congo red staining and polarized-light microscopy. Adverse events were recorded on a questionnaire immediately after the procedure and 7 days, 14 days, and 6 months thereafter. RESULTS: Sixty-four patients (12.7%) reported transient adverse events: 40 paresthesias lasting <7 days, 17 paresthesias lasting <14 days, 27 cases of local swelling, and 8 external hematoma. One patient has had local paresthesia for 2 years. A total of 498 (99.2%) samples provided adequate material for histologic analysis. Of 452 patients evaluated for SS, 378 were finally evaluated. Ninety-three patients (24.5%) had a cumulative focus score > or =1, and 87 (94.5%) of 93 satisfied the AECG criteria. Classification of SS was possible for 124 (32.8%) of 378 patients. In 51 (41%) of 124, MSGB was essential to reach the number of criteria needed for classification. Of 50 patients evaluated for amyloidosis, 10 (20%) had positive Congo red staining. CONCLUSION: MSGB is a simple, safe, and reliable tool for the diagnosis of SS and amyloidosis, and therefore is suitable for more extensive application.
16758083 [Primary biliary cirrhosis: a thirteen years experience]. 2006 Apr BACKGROUND: Primary biliary cirrhosis (PBC) is a chronic cholestatic disease, which can progress to hepatic failure. AIM: To study the clinical presentation, pathological features, treatment and outcome of a group of patients with PBC. MATERIAL AND METHODS: Retrospective review of medical records of 115 patients (110 females, age range 30-76 years) with PBC. Clinical presentation, pathological stage, treatment, outcome and eventual use of liver transplantation, were recorded. RESULT: Seventy eight percent of patients were symptomatic at presentation (itching in 69% and malaise in 62%). Antimitochondrial antibodies were positive in 56%. No clinical or laboratory differences were observed between symptomatic patients or those with positive antimitochondrial antibodies and the rest of the study group. Sjögren syndrome was present in 38%, hypothyroidism in 13%, scleroderma in 7% and rheumatoid arthritis in 5%. Initially, 61% had fibrosis and/or cirrhosis, and ursodeoxycholic acid was indicated in 94% of the patients. Fifteen patients underwent liver transplantation due to upper digestive bleeding or itching. Survival has been 67% at 36 months after transplantation. In one transplanted liver, PBC recurred. CONCLUSIONS: An early diagnosis and treatment of a progressive disease such as PBC will reduce the incidence of complications and the use of costly treatments.
20476908 Pathogenic role of antibodies to citrullinated proteins in rheumatoid arthritis. 2006 May In the last 10 years, the discovery that antibodies to citrullinated proteins are highly specific for rheumatoid arthritis has led to a model of pathogenesis that ties together the genetic and environmental risk factors for susceptibility and severity of disease. The authors propose that the chronic inflammation is driven by two phases of an immune response. The first phase is the priming of autoimmunity, which may occur many years before the onset of disease and is caused by environmental factors, such as smoking and infectious agents, in the context of disease susceptibility alleles. This may occur in sites outside the joint, such as the respiratory tract. The second phase is the induction of arthritis, which is associated with the generation of citrullinated proteins within the joint, which is then perpetuated as the erosive disease by a local chronic immune response. The identity of candidate synovial citrullinated antigen(s), whether fibrin, vimentin, alpha-enolase, collagen type II or others yet to be described, may be the key to the pathogenesis of the destructive disease characteristic of rheumatoid arthritis. There is emerging evidence that citrullination may already be modified by established therapy in rheumatoid arthritis, but more specific inhibitors of deimination may provide new agents for future treatments.
20528552 New models of care for patients with rheumatoid arthritis. 2006 Apr Traditional comprehensive care, involving a team of health professionals from various disciplines, has been widely used in patients with rheumatoid arthritis. However, in many countries, its access and use are hindered by limitations in human and financial resources. Moreover, due to developments in the medical treatment of rheumatoid arthritis and in healthcare and society in general, the patients' needs and demands regarding the contents and organization of comprehensive care are changing. To guarantee the provision of care meeting the varying requirements of rheumatoid arthritis patients throughout the disease trajectory, several new care models are being developed. Some of these models include nurses or other health professionals and general practitioners in care pathways and processes. In other models, organizational aspects play a major role, such as new ways of running early arthritis and direct-access clinics. In addition, an optimal use of information technology may prove to be an important step forward. With all of these developments, aspects such as the patients', as well as healthcare providers', educational needs, continuity, access and funding have to be taken into account. Moreover, evaluations of effectiveness and costs in various healthcare systems and local organizations are needed.