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ID PMID Title PublicationDate abstract
22901967 Prevalence of Sjögren's syndrome with dementia in a memory clinic. 2012 Nov 15 INTRODUCTION: Sjögren's syndrome (SS) is an autoimmune disorder involving the exocrine glands, which affects 1.9-3.0% of the elderly population. Approximately 20% of all patients with SS have CNS involvement, including dementia, as a result of angiitis. AIMS: The aim of the study was to clarify the prevalence and impact of SS among patients in a memory clinic. METHODS: This study prospectively recruited patients with cognitive dysfunction in a memory clinic from 2007 to 2010. In addition to the examinations for dementia, the patients' levels of anti-SSA and SSB antibodies were measured. Schirmer's test and/or a lip biopsy were added if required. SS was diagnosed based on the American European consensus criteria. RESULTS: Out of 276 cases who completed the examinations, 265 (97/168 males/females, mean age: 77.9, median MMSE score: 23) did not demonstrated cognitive decline. Sixteen (6.3%) and seven (2.7%) patients were positive for anti-SS-A and SS-B antibodies, respectively. Twenty patients (7.5%) were diagnosed with primary SS (mean age: 77.2 years old, median MMSE: 21). Seven of these patients had previously been diagnosed with MCI (VCIND: 5, aMCI: 2), and 13 had been diagnosed with dementia. All had asymmetrical focal hypoperfusion on SPECT, and eighteen had subcortical lesions on MRI. Twelve were treated for dementia (median time: 2.1 years), and their MMSE significantly improved (median MMSE: 26, p=0.0019), while the non-SS subjects' MMSE declined (n=126, median: 22). CONCLUSION: The patients with SS accounted for 7.5% of those with a cognitive decline as determined at a memory clinic, and are characterized by subcortical white matter lesions and asymmetric hypoperfusion.
22605541 Protective role of systemic furin in immune response-induced arthritis. 2012 Sep OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune joint disease associated with chronic inflammation of the synovium that causes profound damage of joints. Inflammation results in part from the influx of immune cells secreting inflammatory cytokines and the reduction in the number of Treg cells. We undertook this study to assess the effect of furin, a proteinase implicated in the proteolytic activity of various precursor proteins and involved in the regulation of both proteinase maturation and immune cells, in an experimental model of RA. METHODS: The effect of furin and its inhibitor α1-PDX was tested in mice with collagen-induced arthritis (CIA). Joints were processed for histology and protein expression. Levels of cytokines were measured in joint tissue, and Treg cell numbers were measured in spleens. RESULTS: Furin expression and activity were high in the synovial pannus in RA patients and mice with CIA. Systemic administration of furin prevented increases in the arthritis score, joint destruction, and bone loss, in contrast to systemic administration of the furin inhibitor α1-PDX, which enhanced these parameters. By preventing the development of synovial pannus, furin reduced the expression of metalloproteinases in the joints. In contrast, α1-PDX enhanced synovial proliferation and the expression and activity of matrix metalloproteinases. Furthermore, furin reversed the local Th1/Th2 balance and restored the number of Treg cells in the spleen, indicating mediation by immune cells. CONCLUSION: These findings show the protective role of exogenous furin against RA, mediated by an immune response. The data suggest the potential therapeutic use of furin or its derivatives in autoimmune diseases including RA.
21935585 An evaluation of the impact of seniors on a rheumatology referral clinic: demographics and 2011 Nov The aging population is impacting subspecialty areas outside of geriatrics. Rheumatic diseases increase with age. Therapy for these diseases can add to polypharmacy and negatively impact other comorbidities. This is a retrospective chart review of all patients attending a rheumatology subspeciality clinic over 1 year. Referrals were prescreened and excluded probable degenerative axial and peripheral disease and chronic pain syndromes. Data were collected on demographics, diagnoses, and medications. Two hundred ninety-five new patients were seen. Seventy-eight (26%) were seniors (age, >65 years) with a mean age of 73 years (65-90). Comparing the >65 to <65 age groups, the prevalence of inflammatory arthritides (rheumatoid arthritis (RA), psoriatic arthritis, palindromic rheumatism) was comparable: 48% vs 53%; however, osteoarthritis and polymyalgia rheumatica were twice as common in the older group. Comorbidities in the >65 age group included hypertension (31%), osteoporosis (27%), diabetes (15%), hypothyroidism (11%), and coronary artery disease (9%). Only one patient had documented dementia. There were no cases of uncontrolled hypertension identified, and all patients were receiving a mixture of anti-hypertensives. Eighty-one percent of osteoporosis patients were on antiresorptives, but only 40% of prednisone users were taking bisphosphonates. For RA, treatment was somewhat comparable between the groups, with all but two patients receiving disease-modifying antirheumatic drugs. Eleven percent were on biologics. Seniors comprise a significant number of referrals. Pharmacotherapy differs in seniors, with more use of prednisone and a probable contribution of polypharmacy. This study highlights the need for reciprocal knowledge by both geriatricians and rheumatologists to optimize the management of these complex patients.
21959060 Seropositivity is associated with insulin resistance in patients with early inflammatory p 2011 INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death in patients with inflammatory polyarthritis (IP), especially in seropositive disease. In established rheumatoid arthritis (RA), insulin resistance (IR) is increased and associated with CVD. We investigated factors associated with IR in an inception cohort of patients with early IP. METHODS: Patients with early IP (two or more swollen joints for four or more weeks), aged 18 to 65 years, seen within 24 months of symptom onset were recruited from the Norfolk Arthritis Register (NOAR), a primary-care-based inception cohort. Assessment included joint examination, current and prior therapy and completion of the Health Assessment Questionnaire. Fasting blood was taken for measurement of CVD risk factors, rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), C-reactive protein (CRP), and insulin levels. IR was calculated using the homeostatic model assessment (HOMA-IR). We examined factors associated with IR using univariate and multivariable linear regression models. RESULTS: A total of 196 patients, including 59 (30%) males, were studied with a median (interquartile range, IQR) age and IP symptom duration of 49 (40 to 57) years and 6.7 (4.6 to 10.7) months, respectively. After age and gender adjustment, HOMA-IR was associated with obesity, (β-Coefficient (95% CI); 1.60 (0.96, 2.24)), higher systolic and diastolic blood pressure (0.03 (0.01, 0.05) and 0.04 (0.01, 0.08) respectively), triglycerides (1.06 (0.54, 1.57)), and HDL (-1.38 (-2.17,-0.58)). HOMA-IR was associated with serological status and this association persisted after adjustment for classic CVD risk factors and other IP-related variables (RF β-Coefficient (95% CI); 0.87 (0.20, 1.53) and ACPA β-Coefficient (95% CI); 1.42 (0.70, 2.15)). CONCLUSIONS: Seropositivity for RF or ACPA was associated with IR in this early IP cohort. This association may, in part, explain why seropositive patients have excess CVD mortality.
22288012 Inflammation and immune response of intra-articular serotype 2 adeno-associated virus or a 2012 Intra-articular gene therapy has potential for the treatment of osteoarthritis and rheumatoid arthritis. To quantify in vitro relative gene transduction, equine chondrocytes and synovial cells were treated with adenovirus vectors (Ad), serotype 2 adeno-associated virus vectors (rAAV2), or self-complementary (sc) AAV2 vectors carrying green fluorescent protein (GFP). Using 6 horses, bilateral metacarpophalangeal joints were injected with Ad, rAAV2, or scAAV2 vectors carrying GFP genes to assess the in vivo joint inflammation and neutralizing antibody (NAb) titer in serum and joint fluid. In vitro, the greater transduction efficiency and sustained gene expression were achieved by scAAV2 compared to rAAV2 in equine chondrocytes and synovial cells. In vivo, AAV2 demonstrated less joint inflammation than Ad, but similar NAb titer. The scAAV2 vectors can induce superior gene transduction than rAAV2 in articular cells, and both rAAV2 and scAAV2 vectors were showed to be safer for intra-articular use than Ad vectors.
22751597 The actual role of therapy with traditional disease-modifying antirheumatic drugs in psori 2012 Jul Although several reviews and metaanalyses have shown lack of evidence of efficacy of traditional disease-modifying antirheumatic drugs (DMARD) in psoriatic arthritis (PsA), these drugs are very often used and are recommended by treatment guidelines around the world as first-line therapy for most patients with PsA. Some new investigations showed that higher doses of methotrexate (MTX) are more beneficial for patients with PsA with peripheral involvement. Also, observational studies have shown that retention of MTX for patients with PsA is comparable to that of patients with rheumatoid arthritis (RA), and that with MTX, remission is achievable by around 20% of patients with PsA. Sulfasalazine, leflunomide, and cyclosporine have also been shown to be effective in a small number of patients, although the overall effect on disease activity for these drugs is small. Although combination of anti-tumor necrosis factor agents with traditional DMARD is not mandatory in PsA as it is in RA, there is evidence that some extra benefit might be achieved when combinations are used, not only for the joints but for the skin. There is still room for the use of traditional DMARD in PsA, and for the time being, DMARD should still be considered as first-line therapy for most patients with PsA.
20953422 Electroacupuncture inhibits inflammation reaction by upregulating vasoactive intestinal Pe 2011 Acupuncture is emerging as an alternative therapy for rheumatoid arthritis (RA). However, the molecular mechanism underlying this beneficial effect of acupuncture has not been fully understood. Here, we demonstrated that electroacupuncture at acupoints Zusanli (ST36), Xuanzhong (GB39); and Shenshu (BL23) markedly decreased the paw swelling and the histologic scores of inflammation in the synovial tissue, and reduced the body weight loss in an adjuvant-induced arthritis rat model. However, the electrical stimulation at nonacupoint did not produce any beneficial effects against the experimental arthritis. Most interestingly, the electroacupuncture treatment resulted in an enhanced immunostaining for vasoactive intestinal peptide (VIP), a potent anti-inflammatory neuropeptide, in the synovial tissue. Moreover, the VIP-immunostaining intensity was significantly negatively correlated with the scores of inflammation in the synovial tissue (r = -0.483, P = .0026). In conclusion, these findings suggest that electroacupuncture may offer therapeutic benefits for the treatment of RA, at least partially through the induction of VIP expression.
21780649 [Perspectives of the treatment of rheumatic diseases in the beginning of the XXI century]. 2011 Prevalence of immunoinflammatory diseases in general population is about 10%. Rheumatic diseases, first of all rheumatoid arthritis (RA), are among most prevalent immunoinflammatory diseases. In the first decade of the XXI century great progress was achieved in definition of the mechanisms of RA onset and in development of new approaches to its treatment. The article provides information about novel drugs which are effectively used not only in RA but also in other imunoinflammatory diseases.
21225684 Exacerbation of type II collagen-induced arthritis in apolipoprotein E-deficient mice in a 2011 Apr OBJECTIVE: To explore the bidirectional relationship between the development of rheumatoid arthritis (RA) and atherosclerosis using bovine type II collagen (CII)-immunized B10.RIII apoE(-/-) mice, a murine model of spontaneous atherosclerosis and collagen-induced arthritis (CIA). METHODS: Male B10.RIII apoE(-/-) mice and wild-type controls were immunized with 150 μg of CII emulsified in Freund's complete adjuvant (CFA). The clinical, radiologic, and histopathologic severity of CIA, the levels of circulating IgG1 and IgG2a anti-CII antibodies, the expression of proinflammatory and antiinflammatory cytokines in the joints, and the percentages of Th1, Th17, and Treg lymphocytes in the draining lymph nodes were evaluated during CIA induction. In addition, the size of atherosclerotic lesions was assessed in these mice 8 weeks after CIA induction. RESULTS: B10.RIII apoE(-/-) mice that were immunized with CII and CFA developed an exacerbated CIA that was accompanied by increased joint expression of multiple proinflammatory cytokines and by the expansion in the draining lymph nodes of Th1 and Th17 cells. In contrast, the size of vascular lesions in B10.RIII apoE(-/-) mice was not affected by the development of CIA. CONCLUSION: Our findings indicate that a deficiency in apolipoprotein E and/or its consequences in cholesterol metabolism act as accelerating factors in autoimmunity by promoting Th1 and Th17 inflammatory responses.
22674221 The mesenchymal stem cell marker CD248 (endosialin) is a negative regulator of bone format 2012 Oct OBJECTIVE: CD248 (tumor endothelial marker 1/endosialin) is found on stromal cells and is highly expressed during malignancy and inflammation. Studies have shown a reduction in inflammatory arthritis in CD248-knockout (CD248(-/-) ) mice. The aim of the present study was to investigate the functional effect of genetic deletion of CD248 on bone mass. METHODS: Western blotting, polymerase chain reaction, and immunofluorescence were used to investigate the expression of CD248 in humans and mice. Micro-computed tomography and the 3-point bending test were used to measure bone parameters and mechanical properties of the tibiae of 10-week-old wild-type (WT) or CD248(-/-) mice. Human and mouse primary osteoblasts were cultured in medium containing 10 mM β-glycerophosphate and 50 μg/ml ascorbic acid to induce mineralization, and then treated with platelet-derived growth factor BB (PDGF-BB). The mineral apposition rate in vivo was calculated by identifying newly formed bone via calcein labeling. RESULTS: Expression of CD248 was seen in human and mouse osteoblasts, but not osteoclasts. CD248(-/-) mouse tibiae had higher bone mass and superior mechanical properties (increased load required to cause fracture) compared to WT mice. Primary osteoblasts from CD248(-/-) mice induced increased mineralization in vitro and produced increased bone over 7 days in vivo. There was no decrease in bone mineralization and no increase in proliferation of osteoblasts in response to stimulation with PDGF-BB, which could be attributed to a defect in PDGF signal transduction in the CD248(-/-) mice. CONCLUSION: There is an unmet clinical need to address rheumatoid arthritis-associated bone loss. Genetic deletion of CD248 in mice results in high bone mass due to increased osteoblast-mediated bone formation, suggesting that targeting CD248 in rheumatoid arthritis may have the effect of increasing bone mass in addition to the previously reported effect of reducing inflammation.
23133455 TNF-α Polymorphisms in Juvenile Idiopathic Arthritis: Which Potential Clinical Implicatio 2012 Whether tumor necrosis factor alpha (TNF-α) gene polymorphisms (SNPs) influence disease susceptibility and treatment of patients with juvenile idiopathic arthritis (JIA) is presently uncertain. TNF-α is one of the most important cytokine involved in JIA pathogenesis. Several single nucleotide polymorphisms (SNPs) have been identified within the region of the TNF-α gene but only a very small minority have proven functional consequences and have been associated with susceptibility to JIA. An association between some TNF-α SNPs and adult rheumatoid arthritis (RA) susceptibility, severity and clinical response to anti-TNF-α treatment has been reported. The most frenquetly studied TNF-α SNP is located at -308 position, where a substitution of the G allele with the rare A allele has been found. The presence of the allele -308A is associated to JIA and to a poor prognosis. Besides, the -308G genotype has been associated with a better response to anti-TNF-α therapy in JIA patients, confirming adult data. Psoriatic and oligoarticular arthritis are significantly associated to the -238 SNP only in some works. Studies considering other SNPs are conflicting and inconclusive. Large scale studies are required to define the contribution of TNF-α gene products to disease pathogenesis and anti-TNF-α therapeutic efficacy in JIA.
23095477 [A woman with an ulcer of the leg]. 2012 A 47-year-old woman with a history of ulcerative colitis and rheumatoid arthritis presented with a large ulcer with an erythematous halo of the right lower leg. The clinical course and the histopathological results were indicative of pyoderma gangrenosum.
22279511 Synovitis in spondyloarthritides. 2011 Recent studies using magnetic resonance imaging have suggested that the subchondral bone marrow and the entheses are the sites which are primarily involved in the peripheral and axial inflammation found in patients with spondyloarthritides. Histopathological analyses indicated that the typical morphological features at these sites reflect an inflammation (osteitis) at the bone cartilage interface and in the subchondral bone marrow. This finding implies that synovitis may be of minor importance, especially in comparison to other inflammatory joint diseases such as rheumatoid arthritis. Here, we summarize current available knowledge on synovial involvement in inflammatory processes related to SpA.
22028718 Canadian pregnancy outcomes in rheumatoid arthritis and systemic lupus erythematosus. 2011 Objective. To describe obstetrical and neonatal outcomes in Canadian women with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Methods. An administrative database of hospitalizations for neonatal delivery (1998-2009) from Calgary, Alberta was searched to identify women with RA (38 pregnancies) or SLE (95 pregnancies), and women from the general population matched on maternal age and year of delivery (150 and 375 pregnancies, resp.). Conditional logistic regression was used to calculate odds ratios (OR) for maternal and neonatal outcomes, adjusting for parity. Results. Women with SLE had increased odds for preeclampsia or eclampsia (SLE OR 2.16 (95% CI 1.10-4.21; P = 0.024); RA OR 2.33 (95% CI 0.76-7.14; P = 0.138)). Women with SLE had increased odds for cesarean section after adjustment for dysfunctional labour, instrumentation and previous cesarean section (OR 3.47 (95% CI 1.67-7.22; P < 0.001)). Neonates born to women with SLE had increased odds of prematurity (SLE OR 6.17 (95% CI 3.28-11.58; P < 0.001); RA OR 2.66 (95% CI 0.90-7.84; P = 0.076)) and of SGA (SLE OR 2.54 (95% CI 1.42-4.55; P = 0.002); RA OR 2.18 (95% CI 0.84-5.66; P = 0.108)) after adjusting for maternal hypertension. There was no excess risk of congenital defects in neonates. Conclusions. There is increased obstetrical and neonatal morbidity in Canadian women with RA or SLE.
21590292 Hybrid 18F-FDG PET-MRI of the hand in rheumatoid arthritis: initial results. 2011 Sep 18F-fluorodeoxyglucose PET (18F-FDG PET) is highly sensitive to inflammatory changes within the synovial tissue in rheumatoid arthritis (RA). However, the highest spatial resolution for soft tissue can be achieved with MRI. Here, we report on the first true hybrid PET-MRI examination of the hand in early RA exploiting the advantages of both modalities. PET-MRI was performed with a prototype of an APD-based magneto-insensitive BrainPET detector (Siemens Healthcare, Erlangen, Germany) operated within a standard 3T MR scanner (MAGNETOM Trio, Siemens). PET images were normalized, random, attenuation and scatter-corrected, iteratively reconstructed and calibrated to yield standardized uptake values (SUV) of 18F-FDG uptake. T1-weighted TSE in coronal as well as sagittal orientation prior to and following Gadolinium administration were acquired. Increased 18F-FDG uptake was present in synovitis and tenovaginitis as identified on contrast-enhanced MRI. The tracer distribution was surrounding the metacarpophalangeal joints II and III. Maximum SUV of 3.1 was noted. In RA, true hybrid 18F-FDG PET-MRI of the hand is technically feasible and bears the potential to directly visualize inflammation.
23216920 Development and validation of a chromatographic method for determining Clematichinenoside 2012 Dec 8 BACKGROUND: Clematichinenoside AR is a promising lead compound for the treatment of rheumatoid arthritis. A systematic research for the related impurities in AR bulk samples is still lacking. For the safe use of this natural product in future clinical practice, the structure and content of each constituent, including the main ingredient as well as the impurities in AR bulk sample must be characterized in detail. RESULTS: A simple and stability indicating RP-HPLC method was developed and validated for determining the purity of clematichinenoside AR (AR), a natural product from the roots of Clematis manshurica Rupr. (Ranunculaceae) with the potential of treating rheumatoid arthritis. Five impurities were characterized, and impurity 2 (Clematomandshurica saponin F) is a new triterpenoid saponin isolated from this product. Optimum separation for clematichinenoside AR and five related impurities was carried out on an Agilent octadecylsilane bonded silica gel column (TC-C18, 4.6 mm ×150 mm, 5 μm) using a gradient HPLC method. The validation results showed good sensitivity, specificity, linearity(r2>0.9992) precision(RSD<1.63%), accuracy(recoveries in the range of 95.60%-104.76%) and robustness. Three AR bulk samples containing all the impurities were examined by two methods, and the stability of correction factors for the determination of related impurities was discussed. The proposed stability-indicating method was suitable for the quality control of this natural product. CONCLUSION: Five related impurities of clematichinenoside AR were characterized, including a new triterpenoid saponins firstly found in clematichinenoside AR bulk samples. In the simple chromatographic method for determining clematichinenoside AR and its related impurities in bulk samples, the correction factor was better for the quality control in the relative stable concentrations.
22474524 Inhibitory Effect of Curcumol on Jak2-STAT Signal Pathway Molecules of Fibroblast-Like Syn 2012 Hyperplasia of synovial membrane in rheumatoid arthritis (RA) is a critical pathological foundation for inducing articular injury. The janus kinase and signal transducer and activator of transcription (Jak-STAT) pathway plays a critical role in synovial membrane proliferation induced by platelet-derived growth factor (PDGF). To explore the anti-cell proliferation mechanism of curcumol, a pure monomer extracted from Chinese medical plant zedoary rhizome, the changes of Jak2-STAT1/3 signal pathway-related molecules in synoviocytes were observed in vitro. In this study, the fibroblast-like synoviocytes (FLS) in patients with RA were collected and cultured. The following parameters were measured: cell proliferation (WST-1 assay), cell cycles (fluorescence-activated cell sorting, FACS), STAT1 and STAT3 activities (electrophoretic mobility shift assay, EMSA), and the protein expressions of phosphorylated Jak2, STAT1, and STAT3 (Western blot). It was shown that curcumol could inhibit the RA-FLS proliferation and DNA synthesis induced by PDGF-BB in a dose-dependent manner in vitro. The transcription factors activities of STAT1 and STAT3 were obviously elevated after PDGF-BB stimulation (P < 0.05). Super-shift experiments identified the STAT1 or STAT3 proteins in the complex. Furthermore, the different concentration curcumol could downregulate the DNA binding activities of STAT1 and STAT3 (P < 0.05) and inhibit the phosphorylation of Jak2 while it had no effect on the protein expressions of STAT1 and STAT3. Positive correlations were found between changes of cell proliferation and DNA-binding activities of STAT1 and STAT3, respectively (P < 0.01). In conclusion, curcumol might suppress the FLS proliferation and DNA synthesis induced by PDGF-BB through attenuating Jak2 phosphorylation, downregulating STAT1 and STAT3 DNA-binding activities, which could provide theoretical foundation for clinical treatment of RA.
22263518 [Effects of two antigens for IgM detection of toxoplasmosis]. 2011 Oct OBJECTIVE: To observe the effects of recombinant Toxoplasma gondii P30 antigen and soluble antigen for IgM detection of toxoplasmosis. METHODS: Recombinant Toxoplasma gondii P30 antigen and soluble antigen were coated on two nitrocellulose membranes (NC) respectively. They were combined with the corresponding antibodies in the testing sera. The gold-labeled rabbit anti-human IgM(s) were detected for corresponding antibodies and the positive visualized. The sera of toxoplasmosis, rheumatoid arthritis, Mycoplasma pneumonia, schistosomiasis patients and healthy persons were tested. RESULTS: A total of five kinds of 166 serum samples were detected with dot immunogold filtration assay (DIGFA) of the two antigens respectively. In 38 serum samples of Toxoplasma gondii infection, the sensitivity of P30-DIGFA was 92.1% (35/38) and soluble antigen-DIGFA 81.6% (31/38). There was no significant difference (P > 0.05). Totally 63 normal serum samples showed negative, so the specificity was 100%. In 30 serum samples of rheumatoid arthritis patients, 2 cases were positive in P30-DIGFA and 3 positive in soluble antigen-DIGFA. Totally 25 serum samples of schistosomiasis patients and 10 serum samples of Mycoplasma pneumonia patients showed negative. CONCLUSION: Recombinant Toxoplasma gondii P30 antigen may be developed into clinical diagnostic kits for detection of early or acute toxoplasmosis.
21851606 Accuracy and differential bias in copy number measurement of CCL3L1 in association studies 2011 Aug 18 BACKGROUND: Copy number variation (CNV) contributes to the variation observed between individuals and can influence human disease progression, but the accurate measurement of individual copy numbers is technically challenging. In the work presented here we describe a modification to a previously described paralogue ratio test (PRT) method for genotyping the CCL3L1/CCL4L1 copy variable region, which we use to ascertain CCL3L1/CCL4L1 copy number in 1581 European samples. As the products of CCL3L1 and CCL4L1 potentially play a role in autoimmunity we performed case control association studies with Crohn's disease, rheumatoid arthritis and psoriasis clinical cohorts. RESULTS: We evaluate the PRT methodology used, paying particular attention to accuracy and precision, and highlight the problems of differential bias in copy number measurements. Our PRT methods for measuring copy number were of sufficient precision to detect very slight but systematic differential bias between results from case and control DNA samples in one study. We find no evidence for an association between CCL3L1 copy number and Crohn's disease, rheumatoid arthritis or psoriasis. CONCLUSIONS: Differential bias of this small magnitude, but applied systematically across large numbers of samples, would create a serious risk of false positive associations in copy number, if measured using methods of lower precision, or methods relying on single uncorroborated measurements. In this study the small differential bias detected by PRT in one sample set was resolved by a simple pre-treatment by restriction enzyme digestion.
21169854 Prevalence of subclinical enthesopathy in patients with spondyloarthropathy: an ultrasound 2011 Jan BACKGROUND: Ultrasound has demonstrated to be a highly sensitive tool in the evaluation of entheses in spondyloarthropathy (SpA) patients and improves the ability of clinical examination to detect enthesopathy. OBJECTIVES: The objectives of the study were to determine the prevalence of subclinical enthesopathy in SpA patients and to evaluate the reliability of ultrasound in the detection of abnormal findings indicative of enthesopathy. METHODS: Six hundred lower-limb entheses were assessed in 60 SpA patients without known history of entheseal involvement. Sixty rheumatoid arthritis patients and 30 control subjects were included as control groups. Clinical examination and ultrasound were consecutively performed at each of the entheses to detect signs indicative of enthesopathy. Images from 20 SpA patients were stored and afterward evaluated to determine the reliability of abnormal ultrasound findings. RESULTS: Ultrasound detected a high prevalence of enthesopathy in SpA patients with respect to both rheumatoid arthritis patients and control subjects (P < 0.001 for both comparisons). In SpA patients, clinical examination detected enthesopathy in 56 (9.3%) of 600 entheses. In the remainder 544 clinically asymptomatic entheses (90.7%) (not painful and not swollen), ultrasound detected in 331 (60.8%) at least 1 ultrasound sign of enthesopathy. The intrareader and interreader agreement for all ultrasound abnormal findings was good to excellent. CONCLUSION: The present study demonstrates a higher sensitivity of ultrasound with respect to physical examination in the detection of signs indicative of enthesopathy in SpA patients with an adequate interreader and intrareader reliability. Further study is needed about the prognostic value of the ultrasound findings for predicting clinical onset of entheseal involvement.