Diagnostic value of antibodies against a modified citrullinated vimentin in rheumatoid arthritis

Antibodies directed against citrullinated vimentin are members of the family of autoantibodies reactive with citrullinated proteins and are among the most specific serological markers for the diagnosis of rheumatoid arthritis (RA). This study was performed to test the diagnostic value of a newly developed enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against a genetically modified citrullinated vimentin (anti-MCV) in comparison with a second-generation anti-cyclic citrullinated peptides (anti-CCP2) ELISA test system. Blinded sera from 631 patients (409 consecutive out-patients and 222 randomly selected stored sera) with RA (n = 164) and non-RA (osteoarthritis [n = 120], polymyalgia rheumatica/giant cell arteritis [n = 80], spondyloarthritis [n = 36], and other inflammatory rheumatic or non-inflammatory disease [n = 67]) were tested for the presence of anti-MCV and anti-CCP2 antibodies according to the manufacturers' instructions. The diagnostic performance of the anti-MCV was comparable with the anti-CCP2 assay for the diagnosis of RA according to the calculated area under the curve (0.824; 95% confidence interval (CI) 0.778–0.870 versus 0.818; 95% CI 0.767–0.869) as analysed by receiving operating characteristic curve. When categorised with a cutoff value of 20.0 U/ml (as recommended by the manufacturer), sensitivity and specificity of the anti-MCV ELISA were 69.5% (95% CI 61.9%–76.5%) and 90.8% (86.9%–93.8%), respectively, compared with 70.1% (62.5%–77.0%) and 98.7% (96.7%–99.6%) of the anti-CCP2 assay. Using the cutoff values of 19.0 U/ml and 81.5 U/ml for the anti-MCV test to obtain a sensitivity and specificity identical to the anti-CCP2 assay, showed a reduced specificity (89.8%; 85.8%–92.9%) and sensitivity (53.7%; 45.7%–61.5%), respectively, of the anti-MCV ELISA compared with the anti-CCP2 test. In conclusion, the serum ELISA testing for anti-MCV antibodies as well as the anti-CCP-2 assay perform comparably well in the diagnosis of RA. In the high-specificity range, however, the anti-CCP2 assay appears to be superior to the anti-MCV test

Apoptotic Effects of Antilymphocyte Globulins on Human Pro-inflammatory CD4+CD28− T-cells

BACKGROUND: Pro-inflammatory, cytotoxic CD4(+)CD28(-) T-cells with known defects in apoptosis have been investigated as markers of premature immuno-senescence in various immune-mediated diseases. In this study we evaluated the influence of polyclonal antilymphocyte globulins (ATG-Fresenius, ATG-F) on CD4(+)CD28(-) T-cells in vivo and in vitro. PRINCIPAL FINDINGS: Surface and intracellular three colour fluorescence activated cell sorting analyses of peripheral blood mononuclear cells from 16 consecutive transplant recipients and short-term cell lines were performed. In vivo, peripheral levels of CD3(+)CD4(+)CD28(-) T-cells decreased from 3.7 ± 7.1% before to 0 ± 0% six hours after ATG-F application (P = 0.043) in 5 ATG-F treated but not in 11 control patients (2.9 ± 2.9% vs. 3.9 ± 3.0%). In vitro, ATG-F induced apoptosis even in CD4(+)CD28(-) T-cells, which was 4.3-times higher than in CD4(+)CD28(+) T-cells. ATG-F evoked apoptosis was partially reversed by the broad-spectrum caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk) and prednisolon-21-hydrogensuccinate. ATG-F triggered CD25 expression and production of pro-inflammatory cytokines, and induced down-regulation of the type 1 chemokine receptors CXCR-3, CCR-5, CX3CR-1 and the central memory adhesion molecule CD62L predominately in CD4(+)CD28(-) T-cells. CONCLUSION: In summary, in vivo depletion of peripheral CD3(+)CD4(+)CD28(-) T-cells by ATG-F in transplant recipients was paralleled in vitro by ATG-F induced apoptosis. CD25 expression and chemokine receptor down-regulation in CD4(+)CD28(-) T-cells only partly explain the underlying mechanism

Coalition for Health and Gender Equity (CHANGE)—a protocol for a global cross-sectional survey of health and gender equity in rheumatology

Lay Summary: What does this mean for patients? The CHANGE Study, led by a team of rheumatology professionals worldwide, is working to make health care more equal for everyone. We are focusing on challenges faced by rheumatologists, such as fair pay and career opportunities. To understand these issues better, the team is gathering information through a global survey of rheumatology professionals. The goal is to find out why there are differences and come up with solutions. Ultimately, the aim is to create a fair and inclusive environment in rheumatology, ensuring that everyone has the same chances to grow in their careers, regardless of their gender. The findings of the study will help to create better guidelines, promoting fairness and equality for health-care professionals in rheumatology

Definitions and reliability assessment of elementary ultrasound lesions in giant cell arteritis: a study from the OMERACT Large Vessel Vasculitis Ultrasound Working Group

Objectives: To define the elementary ultrasound (US) lesions in giant cell arteritis (GCA) and to evaluate the reliability of the assessment of US lesions according to these definitions in a web-based reliability exercise. Methods: Potential definitions of normal and abnormal US findings of temporal and extracranial large arteries were retrieved by a systematic literature review. As a subsequent step, a structured Delphi exercise was conducted involving an expert panel of the Outcome Measures in Rheumatology (OMERACT) US Large Vessel Vasculitis Group to agree definitions of normal US appearance and key elementary US lesions of vasculitis of temporal and extracranial large arteries. The reliability of these definitions on normal and abnormal blood vessels was tested on 150 still images and videos in a web-based reliability exercise. Results: Twenty-four experts participated in both Delphi rounds. From originally 25 statements, nine definitions were obtained for normal appearance, vasculitis and arteriosclerosis of cranial and extracranial vessels. The 'halo' and 'compression' signs were the key US lesions in GCA. The reliability of the definitions for normal temporal and axillary arteries, the 'halo' sign and the 'compression' sign was excellent with inter-rater agreements of 91-99% and mean kappa values of 0.83-0.98 for both inter-rater and intra-rater reliabilities of all 25 experts. Conclusions: The 'halo' and the 'compression' signs are regarded as the most important US abnormalities for GCA. The inter-rater and intra-rater agreement of the new OMERACT definitions for US lesions in GCA was excellent

2015 recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients'and clinicians'values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR