Choice of Biologic Therapy for Patients with Rheumatoid Arthritis: The Infection Perspective

Biologicals revolutionized the treatment of Rheumatoid Arthritis (RA). The targeted suppression of key inflammatory pathways involved in joint inflammation and destruction allows better disease control, which, however, comes at the price of an elevated infection risk due to relative immunosuppression. The disease-related infection risk and the infection risk associated with the use of TNF-α inhibitors (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol), rituximab, abatacept and tocilizumab are discussed. Risk factors clinicians need to take into account when selecting the most appropriate biologic therapy for RA patients, as well as precautions and screening concerning a number of specific infections, such as tuberculosis, intracellular bacterial infections, reactivation of chronic viral infections and HIV are reviewed

Construction and psychometric properties of the Belgian Rheumatoid Arthritis Disability Assessment (BRADA) questionnaire : a new tool for the evaluation of activity limitations in patients with rheumatoid arthritis

Objectives: To describe the construction and psychometric properties of the Belgian Rheumatoid Arthritis Disability Assessment (BRADA) questionnaire, a self-report tool to evaluate chronic activity limitations in patients with rheumatoid arthritis (RA). The BRADA was developed to assess the eligibility of patients with RA for financial and social support measures. Methods: The BRADA questionnaire evaluates functioning in 6 functional domains (mobility, nutrition, self care, household tasks, awareness of danger and communication) over the past week and the past 3 months. To assess the psychometric properties of the BRADA, patients with moderate to severe RA filled out the BRADA, HAQ-DI and SF-36 questionnaires twice, with a four-week interval. At each visit, the total number of swollen and tender joints, and global disease activity were recorded. DAS 28 was measured at the first visit. Internal consistency of items per domain was evaluated with Cronbach's alpha method. Intraclass correlation coefficient (ICC) analysis was used to assess test-retest reliability. BRADA scores were compared to HAQ, SF-36 scores and disease activity parameters with Spearman's Rho correlation coefficients to assess construct validity. Results: Experts considered the content and face validity of BRADA to be adequate. Internal consistency was satisfactory for all functional domains (alpha >0.75), as was the test-retest reliability (ICC 0.78). BRADA scores showed excellent correlation with other validated questionnaires in RA (HAQ-DI, SF-36) and with measures of disease activity (VAS, DAS28) (p<0.001). Conclusions: Its psychometric properties indicate that the BRADA questionnaire is a suitable instrument to evaluate disease-specific activity limitations in patients with RA

Assessment of activity limitations with the Health Assessment Questionnaire predicts the need for support measures in patients with rheumatoid arthritis : a multicenter observational study

Objective: This study investigated whether the Health Assessment Questionnaire (HAQ) can be used as an instrument to assess the need for social support measures that address activity limitations and participation issues in patients with rheumatoid arthritis (RA). Methods: This multicenter observational study included patients with RA and disease duration of at least one year, consulting their rheumatologist for routine evaluation of disease activity. In the single study visit data on demographics, disease history and current treatment were collected. DAS28 values were collected to evaluate current RA disease activity. Patients were asked to fill out the HAQ and SF-36 questionnaires. Receiver Operator Characteristics (ROC) curves were constructed to evaluate the performance of the HAQ, SF-36 and DAS28 in predicting the need for nine supporting measures available for chronically ill patients in the Belgian social security system. The expert opinion of the treating rheumatologist was used as a reference. Results: The study included 316 patients with a mean age of 59.8 +/- 12.6 years, disease duration of 11.4 +/- 9.3 years, mean DAS28 values of 2.83 +/- 1.17. Mean HAQ score was 0.95 +/- 0.73, mean SF-36 score 56.5 +/- 21.3. HAQ scores >1 were observed in 39.4% of patients. The area under the HAQ ROC curve was consistently >0.7 and higher for the HAQ than for SF-36 or DAS28 for all support measures. Rheumatologists on average recommended 3.67 support measures. Conclusion: The HAQ score was found to be a good predictor of the need for social support measures in patients with RA

Quantification of IFNγ- and IL17-producing cells after stimulation with citrullinated proteins in healthy subjects and RA patients

Antibodies against citrullinated proteins are highly specific for rheumatoid arthritis (RA) and are currently used as a diagnostic marker. In this study, we wanted to quantify the numbers of T cells that react to a wide range of citrullinated proteins in a wide range of HLA-DR subtypes in order to investigate whether citrullination might create T-cell neo-epitopes and could initiate a universal T-cell response. Therefore, PBMCs from healthy volunteers and RA patients were stimulated with a citrullinated and non-citrullinated cell extract on IFN gamma-ELISpot. We found a significantly higher number of IFN gamma-secreting cells after stimulation with citrullinated proteins compared to non-citrullinated proteins in RA patients (1:14,441 cells vs. 1:32,880 cells) as well as in healthy subjects (1:6,261 reactive cells compared to 1:16,212 cells). Additionally, a higher number of IL17-secreting cells were found after stimulation with citrullinated proteins compared to their non-citrullinated counterparts. Our data indicate that citrulline-dependent T-cell response is not restricted to RA patients but that citrullination as such gives rise to a universal break in tolerance

Citrullinated vimentin as an important antigen in immune complexes from synovial fluid of rheumatoid arthritis patients with antibodies against citrullinated proteins

Introduction: Rheumatoid arthritis (RA) is an inflammatory disease, which results in destruction of the joint. The presence of immune complexes (IC) in serum and synovial fluid of RA patients might contribute to this articular damage through different mechanisms, such as complement activation. Therefore, identification of the antigens from these IC is important to gain more insight into the pathogenesis of RA. Since RA patients have antibodies against citrullinated proteins (ACPA) in their serum and synovial fluid (SF) and since elevated levels of citrullinated proteins are detected in the joints of RA patients, citrullinated antigens are possibly present in IC from RA patients. Methods: IC from serum of healthy persons, serum of RA patients and IC from synovial fluid of RA patients and Spondyloarthropathy (SpA) patients were isolated by immunoprecipitation. Identification of the antigens was performed by SDS-PAGE, mass spectrometry and immunodetection. The presence of citrullinated proteins was evaluated by anti-modified citrulline (AMC) staining. Results: Circulating IC in the serum of RA patients and healthy controls contain fibrinogen beta and fibronectin, both in a non-citrullinated form. Additionally, in IC isolated from RA SF, fibrinogen. and vimentin were identified as well. More importantly, vimentin and a minor portion of fibrinogen beta were found to be citrullinated in the isolated complexes. Moreover these citrullinated antigens were only found in ACPA+ patients. No citrullinated antigens were found in IC from SF of SpA patients. Conclusions: Citrullinated fibrinogen beta and citrullinated vimentin were found in IC from SF of ACPA+ RA patients, while no citrullinated antigens were found in IC from SF of ACPA-RA patients or SpA patients or in IC from serum of RA patients or healthy volunteers. The identification of citrullinated vimentin as a prominent citrullinated antigen in IC from SF of ACPA+ RA patients strengthens the hypothesis that citrullinated vimentin plays an important role in the pathogenesis of RA

Analysing wear in carpets by detecting varying local binary patterns

Currently, carpet companies assess the quality of their products based on their appearance retention capabilities. For this, carpet samples with different degrees of wear after a traffic exposure simulation process are rated with wear labels by human experts. Experts compare changes in appearance in the worn samples to samples with original appearance. This process is subjective and humans can make mistakes up to 10% in rating. In search of an objective assessment, research using texture analysis has been conducted to automate the process. Particularly, Local Binary Pattern (LBP) technique combined with a Symmetric adaptation of the Kullback-Leibler divergence (SKL) are successful for extracting texture features related to the wear labels either from intensity and range images. We present in this paper a novel extension of the LBP techniques that improves the representation of the distinct wear labels. The technique consists in detecting those patters that monotonically change with the wear labels while grouping the others. Computing the SKL from these patters considerably increases the discrimination between the consecutive groups even for carpet types where other LBP variations fail. We present results for carpet types representing 72% of the existing references for the EN1471:1996 European standard

Feature extraction of the wear label of carpets by using a novel 3D scanner

In the textile industry, the quality of carpets is still determined through visual assessment by human experts. Human assessment is somewhat subjective, so there is a need for a more objective assessment which yields to automated systems. However, existing computer models are at this moment not yet capable of matching the human expertise. Most attempts at automated assessment have focused on image analysis of two dimensional images of worn carpet. These do not adequately capture the three dimensional structure of the carpet that is also evaluated by the experts and the image processing is very dependent on the lighting conditions. One previous attempt however used a laser scanner to obtain three dimensional images of the carpet and process them for carpet assessment. This paper describes the development of a new scanner to acquire wear label characteristics in three dimensions based on a structured light pattern. Now an appropriate technique based on the local binary patterns (LBP) and the Kullback-Leibler divergence has been developed. We show that the new laser scanning system is less dependent on the lighting conditions and color of the carpet and obtains data points on a structured grid instead of sparse points. The new system is also more than five times cheaper, scans more than seven times faster and is specifically designed for scanning carpets instead of 3D objects. Previous attempts to classify the carpet wear were based on several extracted features. Only one of them - the height difference between worn and unworn part - showed a good correlation of 0.70 with the carpet wear label. However, experiments demonstrate that our approach - using the LBP technique - gives rise to promising results, with correlation factors from 0.89 to 0.99 between the Kullback-Leibler divergence and quality labels. This new laser scanner system is a significant step forward in the automated assessment of carpet wear using 3D images

Texture wear analysis in textile floor coverings by using depth information

Considerable industrial and academic interest is addressed to automate the quality inspection of textile floor coverings, mostly using intensity images. Recently, the use of depth information has been explored to better capture the 3D structure of the surface. In this paper, we present a comparison of features extracted from three texture analysis techniques. The evaluation is based on how well the algorithms allow a good linear ranking and a good discriminance of consecutive wear labels. The results show that the use of Local Binary Patterns techniques result in a better ranking of the wear labels as well as in a higher amount of discrimination between features related to consecutive degrees of wear