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ID PMID Title PublicationDate abstract
19148655 [Psoriatic arthritis. Treatment outcome parameters]. 2009 Feb Psoriatic arthritis (PsA) has increasingly attracted the attention of clinical research in recent years with regard to long-term clinical registries, studies on epidemiology, genetics, and therapy. However, the methodology for assessing disease activity, damage and progression, as well as the resulting definition of treatment outcome parameters have progressed far less in PsA as compared to other rheumatic diseases such as rheumatoid arthritis (RA). Most of the assessment methodologies have been adapted from clinical trials on RA, ankylosing spondylitis, or psoriasis, but have not yet been validated for use in PsA. This article gives an overview of general rheumatological and PsA-specific assessment methods and outcome parameters of PsA therapy.
20018023 Haplotype association analysis of North American Rheumatoid Arthritis Consortium data usin 2009 Dec 15 The Genetic Analysis Workshop 16 rheumatoid arthritis data include a set of 868 cases and 1194 controls genotyped at 545,080 single-nucleotide polymorphisms (SNPs) from the Illumina 550 k chip. We focus on investigating chromosomes 6 and 18, which have 35,574 and 16,450 SNPs, respectively. Association studies, including single SNP and haplotype-based analyses, were applied to the data on those two chromosomes. Specifically, we conducted a generalized linear model with regularization (rGLM) approach for detecting disease-haplotype association using unphased SNP data. A total of 444 and 43 four-SNP tests were found to be significant at the Bonferroni corrected 5% significance level on chromosome 6 and 18, respectively.
20567251 Geoepidemiology of autoimmune rheumatic diseases. 2010 Aug The accumulative global burden of autoimmune and inflammatory rheumatic diseases is substantial. Studying the distribution of these conditions across various global regions and ethnic groups by means of geoepidemiology might readily provide epidemiological data and also advance our understanding of their genetic and environmental underpinnings. In order to depict the geoepidemiology of autoimmune and inflammatory rheumatic diseases, namely rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, ankylosing spondylitis and Sjögren's syndrome, we present a comprehensive collection of epidemiological reports from various world regions, including the prevalence of each of these conditions. The accumulated data show that the reviewed rheumatic diseases are global phenomena, and, with some variance, seem to be relatively evenly distributed. This finding is in contrast with the obviously uneven distribution of some major nonrheumatic autoimmune conditions. In addition, geoepidemiology demonstrates that ethnogenetic susceptibility interacts with lifestyle and environmental factors, which include socioeconomic status, infectious agents (triggering or protective agents), environmental pollutants, and vitamin D (dependent on sunlight exposure), in determining the risk of developing rheumatic autoimmunity.
20018067 A two-stage search strategy for detecting multiple loci associated with rheumatoid arthrit 2009 Dec 15 Gene x gene interactions play important roles in the etiology of complex multi-factorial diseases like rheumatoid arthritis (RA). In this paper, we describe our use of a two-stage search strategy consisting of information theoretic methods and logistic regression to detect gene x gene interactions associated with RA using the data in Problem 1 of Genetic Analysis Workshop 16. Our method detected interactions of several SNPs (single-SNP and SNP x SNP) that are located on chromosomal regions linked to RA and related diseases in previous studies.
19893395 Type two or localized endobronchial non-Hodgkin lymphoma. 2009 Oct We present chest x-ray, chest CT, and FDG PET images of a patient diagnosed with endobronchial lymphoma. The commonly involved thoracic structures in non-Hodgkin lymphoma are mediastinal lymph nodes. Non-Hodgkin lymphoma involving the tracheobronchial tree is rare. Localized primary endobronchial lymphoma confined to the tracheobronchial tree with no dissemination classified as type-2 is extremely rare. This is a report describing the type-2 endobronchial DLBCL. The patient also had a history of rheumatoid arthritis and was treated with methotrexate for 10 years. The other interesting aspect of this case is its association with rheumatoid arthritis and methotrexate treatment. Although there are reports documenting this type of association in the literature, there is almost no documented evidence of this association specifically with type-2 endobronchial non-Hodgkin lymphoma.
19358841 Inhibition of cathepsin K reduces bone erosion, cartilage degradation and inflammation evo 2009 Jun 24 Cathepsin K (EC 3.4.22.38) is expressed by osteoclasts and synovial fibroblasts and its proteolytic activity is hypothesized to play a role in the pathology of rheumatoid arthritis. This study explored the effects of the cathepsin K inhibitor N-(1-{[(Cyanomethyl)amino]carbonyl}cyclohexyl)-4-[2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]benzamide (L-006235) in murine collagen-induced arthritis. L-006235 is a potent inhibitor of recombinant human and murine cathepsin K, enzymes (K(i):0.073 nM and IC(50): 2.4 nM, respectively) and at the cellular level in human osteoclasts (IC(50): 28 nM) with ~1000-fold selectivity against cathepsin S. L-006235 did not result in splenic invariant chain p10 accumulation, a specific marker of cathepsin S inhibition. L-006235 was dosed daily (25 mg/kg, p.o.), either prophylactically (days 0-42) or therapeutically (14 days post onset of disease) to DBA/1J mice subjected to collagen-induced arthritis. Disease severity was scored during the course of the study. Histological evaluation of cartilage and bone degradation together with related biomarkers namely, deoxypyridinoline, cartilage oligomeric matrix protein and C-terminal telopeptide degradation product of type I collagen (CTX-I) were analyzed after the study. After prophylactic or therapeutic administration, L-006235 significantly reduced biomarkers reflecting bone and cartilage degradation. Pathological changes at the histological level were significantly reduced after prophylactic treatment (P<0.01), but not after therapeutic treatment. Prophylactic treatment with L-006235 delayed disease onset (P<0.01) and reduced the disease severity score (P<0.05). Inhibition of cathepsin K activity exerts beneficial effects on collagen-induced arthritis in mice and thus warrants further investigation as a therapeutic intervention in human rheumatoid arthritis.
19327233 Apolipoprotein A-I and cholesterol in synovial fluid of patients with rheumatoid arthritis 2009 Jan OBJECTIVE: To investigate lipid and apolipoprotein (Apo) levels in synovial fluid (SF) and serum of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and osteoarthritis (OA). METHODS: SF of 44 patients (14 RA, 14 PsA, 16 OA) was tested for Apo A-I, HDL-C, total cholesterol (TC), IL-1Beta, TNF-alpha, white blood cell count (WBC) and polymorphonucleate (PMN) percentage. Blood samples, collected simultaneously to the SF, were examined for Apo A-I, HDL-C, TC, TNF-alpha, serum amyloid A (SAA) and C-reactive protein (CRP). Thirty-three healthy donors served as a control group. RESULTS: Serum levels of Apo A-I, HDL-C and TC were higher in OA as compared with RA, PsA and the control group. The patients with inflammatory arthritis had lower serum levels of Apo A-I and HDL-C than did the controls. Apo A-I concentrations were higher in SF of RA patients, while PsA showed the highest concentration of TC, though not reaching statistical significance. A negative correlation was found between serum Apo A-I and synovial WBC (r=-0.48 p=0.002) and IL-1Beta (r=-0.42 p=0.016). There was a strong positive correlation between the Apo A-I SF/serum ratio and synovial WBC (r=0.73 p<0.001), IL-1Beta (r=0.68 p<0.001) and a weak, yet significant, correlation with serum CRP (r=0.49 p=0.002) and SAA (r=0.41 p=0.008). CONCLUSION: Our study confirms that in RA Apo A-I and TC levels are decreased in plasma and increased in SF, thus suggesting infiltration of HDL particles in the inflamed joint with inhibition of the local production of proinflammatory cytokines. On the other hand, it can be hypothesized that the sequestration of Apo A-I in the inflamed tissue may, in part, account for the reduction of circulating HDL and the excess cardiovascular risk in RA and PsA patients.
19240826 A case of idiopathic bursal synovial chondromatosis resembling rheumatoid arthritis. 2009 Jan Primary synovial osteochondromatosis is an unusual condition, which generally involves otherwise normal joints. Joints commonly affected in descending order of frequency are knee, hip, glenohumeral joint, elbow and ankle, though any articulation may be involved. Synovial osteochondromatosis has been also encountered in tendon sheaths and periarticular bursa. We report a case with the clinical findings, radiographic features, surgical and histological data of primary subacromial-subdeltoid bursa synovitis. X-ray radiographs of the right glenohumeral joint as well as CT and MRI of the right shoulder zone were performed. A soft tissue mass around the lateral margin of the proximal humerus without evidence of any calcification/ossification or erosion of the adjacent cortex was detected on both X-Rays and CT images. Multiple nodules of almost equal size appeared that were isointense on T1-weighted spin-echo images and slightly hyperintense on T2 weighted spin-echo images compared with the signal intensity of the surrounding skeletal muscles. The main differential diagnosis was pigmented villonodular synovitis, rheumatoid arthritis with rice bodies and secondary synovial osteochondromatosis. Based on the results of all modalities the diagnosis of primary synovial chondromatosis of subdeltoid/ subacromial bursa was concluded.
18926919 Evolutionarily conserved antigens in autoimmune disease: implications for an infective aet 2009 Feb The immune system has evolved to eliminate or inactivate infectious organisms. An inappropriate response against self-components (autoantigens) can result in autoimmune disease. Here we examine the hypothesis that some evolutionarily conserved proteins, present in pathogenic and commensal organisms and their hosts, provide the stimulus that initiates autoimmune disease in susceptible individuals. We focus on seven autoantigens, of which at least four, glutamate decarboxylase, pyruvate dehydrogenase, histidyl-tRNA synthetase and alpha enolase, have orthologs in bacteria. Citrullinated alpha-enolase, a target for autoantibodies in 40% of patients with rheumatoid arthritis, is our main example. The major epitope is highly conserved, with over 90% identity to human in some bacteria. We propose that this reactivity of autoantibodies to shared sequences provides a model of autoimmunity in rheumatoid arthritis, which may well extend to other autoimmune disease in humans.
19252516 Is tocilizumab in combination with traditional DMARDs safe and effective for patients with 2009 Mar The interleukin 6 receptor antagonist tocilizumab was investigated in a 24-week, phase III randomized controlled trial for the treatment of active, DMARD-resistant rheumatoid arthritis (TOWARD study). The results indicated that the combination of tocilizumab with standard DMARDs produced a significantly higher clinical response rate than DMARDs alone, according to American College of Rheumatology and European League Against Rheumatism response criteria. Evaluation of adverse events revealed that tocilizumab had a good safety profile, although a slightly increased rate of infections, neutropenia, elevated liver enzyme levels and increased lipid levels were observed in some individuals. Further investigations will be required, however, to clarify which DMARD-tocilizumab combinations provide the best efficacy and safety profile in daily clinical practice and to exclude potential risks associated with long-term interleukin 6 blockade. In conclusion, the introduction of tocilizumab was shown to represent a safe and effective therapeutic approach for the treatment of rheumatoid arthritis refractory to treatment with DMARDs alone, which could substantially improve our treatment options for this condition.
19190621 Are static resting wrist splints beneficial in early RA? 2009 Mar In a randomized controlled trial, Adams et al. compared the effectiveness of static resting wrist splints plus occupational therapy with occupational therapy alone in 120 patients with early rheumatoid arthritis. Self-reported adherence with splint wear was moderate, with 24.5% of patients reporting that they had never worn the splints over the 12-month study period. Except for a small benefit of resting splints in the occurrence, but not the duration, of hand morning stiffness, there were no significant differences in structural impairment and functional hand ability outcomes between the control and splint groups. The findings of this trial are in line with the negative outcomes of earlier studies of static resting wrist splints in patients with longer disease duration. The currently available data suggest, therefore, that resting wrist splints might not be an effective routine treatment for patients with rheumatoid arthritis.
21160590 Role of cardiovascular imaging in systemic autoimmune diseases. 2010 Aug 26 Systemic autoimmune diseases are characterized by an excess of cardiovascular (CV) morbidity and mortality compared to the general population, mainly due to chronic inflammation that promotes the development of endothelial dysfunction and enhanced atherosclerosis. Early diagnosis of silent CV involvement is mandatory to improve the long term prognosis of these patients and CV imaging provides valuable information as a reliable diagnostic tool. Transthoracic echocardiography, with several applications (e.g. coronary flow reserve evaluation, tissue Doppler imaging, speckle tracking and the transesophageal approach), represents a first line evaluation, in association with biomarkers of endothelial dysfunction, such as asymmetric dimethylarginine. Nuclear medicine provides useful information on myocardial perfusion. The aim of this editorial is to provide a brief but complete review of the diagnostic tools available for screening and follow up of CV involvement in systemic autoimmune diseases.
27789992 Association of periodontitis with rheumatoid arthritis and atherosclerosis: Novel paradigm 2010 There is increasing documentation of a link between inflammatory periodontal disease affecting the supporting structure of teeth, rheumatoid arthritis, and coronary artery disease. Periodontitis is initiated predominantly by Gram-negative bacteria and progresses as a consequence of the host inflammatory response to periodontal pathogens. Lipopolysaccharide, a cell wall constituent stimulates the production of inflammatory cytokines via the activation of signaling pathways perpetuating inflammatory pathogenesis in a cyclical manner in susceptible individuals; with an element of autoimmune stimulation, not dissimilar to the sequential events seen in RA. Periodontitis, also implicated as a risk factor for cardiovascular disease, promotes mechanisms for atherosclerosis by enhancing an imbalance in systemic inflammatory mediators; more direct mechanisms attributed to microbial products are also implicated in both RA and atherogenesis. Severe periodontal disease characterized by clinical and radiographic parameters has been associated with ischemic stroke risk, significant levels of C-reactive protein and serum amyloid A, amongst others common to both periodontitis and atherosclerosis. Existing data supports the hypothesis that persistent localized infection in periodontitis may influence systemic levels of inflammatory markers and pose a risk for RA and atherosclerosis. A common nucleus of activity in their pathogeneses provides novel paradigms of therapeutic targeting for reciprocal benefit.
20140191 A variant of TNFR2-Fc fusion protein exhibits improved efficacy in treating experimental r 2010 Feb 5 Etanercept, a TNF receptor 2-Fc fusion protein, is currently being used for the treatment of rheumatoid arthritis (RA). However, 25% to 38% of patients show no response which is suspected to be partially due to insufficient affinity of this protein to TNFalpha. By using computational protein design, we found that residue W89 and E92 of TNFR2 were critical for ligand binding. Among several mutants tested, W89Y/E92N displayed 1.49-fold higher neutralizing activity to TNFalpha, as compared to that of Etanercept. Surface plasmon resonance (SPR) based binding assay revealed that the equilibrium dissociation constant of W89Y/E92N to TNFalpha was 3.65-fold higher than that of Etanercept. In a rat model of collagen-induced arthritis (CIA), W89Y/E92N showed a significantly better ability than Etanercept in reducing paw swelling and improvement of arthritic joint histopathologically. These data demonstrate that W89Y/E92N is potentially a better candidate with improved efficacy in treating RA and other autoimmune diseases.
20969551 Psoriatic arthritis - update on pathophysiology, assessment, and management. 2010 Psoriatic arthritis (PsA) is classified as a spondyloarthropathy and characterized by synovitis, enthesitis, dactylitis, and spondylitis, usually manifesting in a person with skin and nail psoriasis. Our understanding about the PsA disease state, its genetics, pathophysiology, and comorbidities, as well as our ability to assess and treat the disease, has advanced as a result of significant collaborative efforts by rheumatologists and dermatologists. This work has been primarily in the development of classification criteria, outcome measures to assess the various clinical domains, and treatment trials with agents also used for diseases such as rheumatoid arthritis (RA) and psoriasis. Biologic agents, especially the anti-TNFs, have demonstrated significant efficacy and reasonable safety in all clinical domains of the disease, resulting in amelioration of clinical symptoms, inhibition of structural damage, and improvement of function and quality of life. A number of advances in assessment and treatment have occurred in the last few years, which are highlighted in this update. This article reviews assessment and treatment of PsA, with an emphasis on recent data.
19326836 Salmonella septic arthritis involving multiple joints in a girl with acute lymphoblastic l 2009 Feb Septic arthritis due to Salmonella has been reported frequently, but multiple joint involvements have rarely been reported in children. A 3-year-old girl presented with Salmonella arthritis involving multiple joints. Laboratory investigations revealed pancytopenia inconsistent with diagnosis of juvenile rheumatoid arthritis or septic arthritis. Bone marrow examination 2 weeks later confirmed the diagnosis of acute lymphoblastic leukemia (ALL). Immunophenotyping studies were consistent with a diagnosis of pre-B ALL. This case illustrates that a delay in the diagnosis may occur when there is an apparent infection focus without classic features of leukemia. Multiple joints involvement of septic arthritis associated with pancytopenia should highlight the possibility of underlying hematologic disorders.
20827333 The efficacy of shikonin on cartilage protection in a mouse model of rheumatoid arthritis. 2010 Aug The potential therapeutic action of shikonin in an experimental model of rheumatoid arthritis (RA) was investigated. As a RA animal model, DBA/1J mice were immunized two times with type II collagen. After the second collagen immunization, mice were orally administered shikonin (2 mg/kg) once a day for 35 days, and the incidence, clinical score, bone mineral density (BMD), bone mineral content (BMC) and joint histopathology were evaluated. BMD in the proximal regions of the tibia largely increased in the shikonin treatment group compared with the control group. We also examined the effect of shikonin on inflammatory cytokines and cartilage protection. Shikonin treatment significantly reduced the incidence and severity of collagen-induced arthritis (CIA), markedly abrogating joint swelling and cartilage destruction. Shikonin also significantly inhibited the production of matrix metalloproteinase (MMP)-1 and up-regulated tissue inhibitors of metalloproteinase (TIMP)-1 in mice with CIA. In conclusion, shikonin exerted therapeutic effects through regulation of MMP/TIMP; these results suggest that shikonin is an outstanding candidate as a cartilage protective medicine for RA.
19445445 Pulmonary manifestations of primary Sjögren's syndrome. 2009 Apr Sjögren's syndrome (SS) is a complex autoimmune exocrinopathy with multifactorial pathogenesis and multisystem manifestation. It is called primary Sjögren's syndrome (PSS) when the manifestations are seen without any other co-existent rheumatic diseases. The incidence of respiratory system involvement varies widely in the reported medical literature, partly due to lack of a universal agreement over the diagnostic criteria of the disease and the type of study methods employed. Respiratory system manifestations are protean; upper airway symptoms are very common and so is the complaint of dry cough. The PSS patients may develop interstitial lung diseases (ILDs) such as usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), lymphocytic interstitial pneumonia (LIP), bronchiolitis obliterans and organising pneumonia (BOOP), etc. They may also develop the whole spectrum of lymphoproliferative disorders of the lung ranging from LIP to follicular bronchiolitis, nodular lymphoid hyperplasia and low-grade lymphomas. Therapeutic options include symptomatic and supportive measures and corticosteroids as the mainstay of the treatment for ILDs occurring in these patients. In recent years, rituximab (anti-CD20) has emerged as a promising treatment for this disease, though data from controlled trials are still lacking. Pulmonary involvement may be a source of significant morbidity in these patients, though only rarely, it is the cause of death.
20850283 [Juvenile Gougerot Sjögren syndrome: report of 3 cases]. 2010 Nov Gougerot Sjögren syndrome is rare during childhood. Diagnosis in adult patients is usually based on sets of criteria combining clinical, serological, and salivary gland histopathological findings. In the pediatric age group, clinical manifestations might be different from the adult form. We report on 3 cases of childhood Gougerot Sjögren syndrome.
20673706 Haralampos M. Moutsopoulos: a lifetime in autoimmunity. 2010 Nov Three years ago, the Journal of Autoimmunity and Autoimmunity Reviews launched a series of special issues devoted to the contributions of outstanding scholars in autoimmunology. The special issues are devoted not only to recognize achievements, but also to include a series of dedicated papers that reflect the scholar's work, but also are cutting-edge research and reviews in immunology. This special issue is devoted to Haralampos M. Moutsopoulos of the National University of Athens. His contributions to patient care, teaching, and original research are legion. The papers that are included reflect not only a wide range of scholarship in autoimmunology, but importantly are written by his colleagues and friends, and by former students. They encompass original scholarship in Sjögren's syndrome, but also in a number of effector pathways in both adult and pediatric autoimmunology.