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.
Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There ...are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, microscope components and conjugate. Newer developments on ANA testing that offer novel features adopted by some clinical laboratories include automated computer-assisted diagnosis (CAD) systems and solid phase assays (SPA).
A group of experts reviewed current literature and established recommendations on methodological aspects of ANA testing. This process was supported by a two round Delphi exercise. International expert groups that participated in this initiative included (i) the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group "Autoimmunity Testing"; (ii) the European Autoimmune Standardization Initiative (EASI); and (iii) the International Consensus on ANA Patterns (ICAP).
In total, 35 recommendations/statements related to (i) ANA testing and reporting by HEp-2 IFA; (ii) HEp-2 IFA methodological aspects including substrate/conjugate selection and the application of CAD systems; (iii) quality assurance; (iv) HEp-2 IFA validation/verification approaches and (v) SPA were formulated. Globally, 95% of all submitted scores in the final Delphi round were above 6 (moderately agree, agree or strongly agree) and 85% above 7 (agree and strongly agree), indicating strong international support for the proposed recommendations.
These recommendations are an important step to achieve high quality ANA testing.
The establishment of the International Consensus on ANA Patterns (ICAP) in 2014-2015 was welcomed by members of the medical community as a significant improvement in guiding harmonization of ANA test ...interpretation and reporting. In the subsequent years, several itinerant meetings and continuous interaction with the community contributed to disseminate the ICAP harmonization on the immunofluorescence patterns observed in the indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA) and to promote progressive improvement in the classification of HEp-2 IFA patterns. The 6th ICAP Workshop was held in person on September 6, 2021 as a satellite meeting of the 15th Dresden Symposium on Autoantibodies. This article summarizes the major discussions at the meeting as well as outlining the current plans for the ICAP committee.
Abstract
Background:
Detection of anti-neutrophil cytoplasmic antibodies (ANCA) is important for the diagnosis of the ANCA-associated vasculitides (AAV). For AAV, especially ANCA directed against ...myeloperoxidase (MPO) and proteinase 3 (PR3) are most relevant. ANCA with less well-defined specificities may, however, also be detected in other inflammatory and non-inflammatory conditions.
Methods:
A questionnaire, initiated by the European Autoimmunity Standardisation Initiative (EASI), was used to gather information on methods and testing algorithms used for ANCA in clinical laboratories of 12 European countries (EASI survey).
Results:
Four hundred and twenty-nine responses were included in the EASI survey analysis which revealed differences within countries and between countries. Laboratories overall were poor in adherence to international consensus on ANCA testing. Substantial variation was observed with respect to the use of ANCA indirect immunofluorescence (IIF) in the algorithm, application of distinct methods for MPO- and PR3-ANCA, the daily availability of new ANCA results, and interpretation of test results.
Conclusions:
Awareness of these differences may stimulate further harmonization and standardization of ANCA testing. This may be promoted by an update of the international ANCA consensus and the introduction of international standards.
To compare current definitions of remission and relapse in polymyalgia rheumatica (PMR) with items resulting from a Delphi-based expert consensus.
Relevant studies including definitions of PMR ...remission and relapse were identified by literature search in PubMed. The questionnaire used for the Delphi survey included clinical (n=33), laboratory (n=54) and imaging (n=7) parameters retrieved from a literature search. Each item was assessed for importance and availability/practicability, and limits were considered for metric parameters. Consensus was defined by an agreement rate of ≥80%.
Out of 6031 articles screened, definitions of PMR remission and relapse were available in 18 and 34 studies, respectively. Parameters used to define remission and/or relapse included history and clinical assessment of pain and synovitis, constitutional symptoms, morning stiffness (MS), physician's global assessment, headache, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood count, fibrinogen and/or corticosteroid therapy. In the Delphi exercise a consensus was obtained on the following parameters deemed essential for definitions of remission and relapse: patient's pain assessment, MS, ESR, CRP, shoulder and hip pain on clinical examination, limitation of upper limb elevation, and assessment of corticosteroid dose required to control symptoms.
Assessment of patient's pain, MS, ESR, CRP, shoulder pain/limitation on clinical examination and corticosteroid dose are considered to be important in current available definitions of PMR remission and relapse and the present expert consensus. The high relevance of clinical assessment of hips was unique to this study and may improve specificity and sensitivity of definitions for remission and relapse in PMR.
One of the main goals of the European Autoimmunity Standardisation Initiative (EASI) is the harmonisation of test-algorithms for autoantibodies related to systemic autoimmune rheumatic diseases ...(SARD).
A questionnaire was used to gather information on methodology, interpretation, and the algorithm for detection of anti-nuclear antibodies (ANA) in relation to their antigen-specificity. The questionnaire was sent to 1200 laboratories in 12 European countries.
The response rate was 47.2%. The results reveal not only apparent differences between countries, but also within countries.
Awareness of these differences may as such already stimulate harmonisation, but the observed differences may also direct recommendations that may further contribute to achieving the EASI goal of harmonisation of autoimmune diagnostics for SARD.
To evaluate factors influencing injection patterns and patient evaluations of an autoinjector device in biologic-naïve patients beginning golimumab (GLM) treatment.
GO-MORE was an open-label, ...multinational, prospective study in patients with active rheumatoid arthritis (RA) (28-joint disease activity score based on erythrocyte sedimentation rate DAS28-ESR ≥3.2). Patients injected 50 mg subcutaneous GLM once monthly for 6 months. Patients reported use preferences and autoinjector evaluations by questionnaire. Responses were analysed descriptively. Effects of patient variables were evaluated with chi-square tests or t-tests.
Of 3,280 efficacy-evaluable patients, 67.7% self-injected with the autoinjector. Compared with patients who self-injected, patients who had someone else administer injections had greater baseline disease activity (e.g., DAS28-ESR 5.84 vs. 6.23, respectively), but not more tender/swollen joints in hands/wrists. Month 6 efficacy was greater for patients who self-injected. In those who self-injected, injection site (thigh 75.2%; 1,563/2,077, abdomen 17.4%; 363/2,077, upper arm 7.2%; 151/2,077) was not associated with wrist swelling or tender/swollen joints in the hand used for injection. Autoinjector ratings were similar across injection sites, yet less pain/discomfort was associated with abdomen injection. Patient autoinjector ratings were favourable overall (e.g. ease of use, pain). Patients with baseline functional impairment had slightly less favourable ratings.
Biologic-naïve patients who self-injected had less baseline disease activity and higher response rates than patients who did not self-inject. Although patients prefer to inject in the thigh, injection in the belly may be less painful. Most patients who self-injected had favourable autoinjector evaluations; patients with functional impairment had slightly less favourable ratings.
Abstract
Special conditions associated with laboratory autoimmune testing are not well compatible with recent developments in regulatory frameworks such as EN/ISO 15189 accreditation or in vitro ...diagnostic medical device regulation (IVD-R). In addition, international recommendations, guidelines and disease criteria are poorly defined with respect to requirements on autoantibody testing. Laboratory specialists from Austria, Belgium, Croatia, Estonia, Finland, France, Germany, Greece, Hungary, Italy, Norway, Poland, Portugal, South Africa, Spain, Sweden, Switzerland, and The Netherlands collected information, reported national experience, and identified quality issues in relation to autoantibody testing that require consensus on interpretation of the regulatory frameworks and guidelines. This process has been organized by the European Autoimmunity Standardisation Initiative (EASI). By identifying the critical items and looking for a consensus, our objective was to define a framework for, in particular, EN/ISO accreditation purposes. Here, we present a review of current publications and guidelines in this field to unify national guidelines and deliver in this way a European handout on quality control and accreditation for laboratories involved in autoantibody testing. We focus on quality items that can be checked during accreditation visits. Despite various local varieties, we encountered an overwhelming dedication to quality assurance in all contributing countries.
Background. Rheumatoid arthritis is a systemic autoimmune disease characterized by joint erosions, progressive focal bone loss, and chronic inflammation. Methods. 20 female patients with ...moderate-to-severe rheumatoid arthritis were treated with anti-TNF-antibody adalimumab in addition to concomitant antirheumatic therapies. Patients were assessed for overall disease activity using the DAS28 score, and neopterin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) concentrations as well as osteoprotegerin (OPG) and soluble receptor activator of NF-κB ligand (sRANKL) concentrations were determined before therapy and at week 12. Neopterin as well as OPG and sRANKL were determined by commercial ELISAs. Results. Before anti-TNF therapy patients presented with high disease activity and elevated concentrations of circulating inflammatory markers. OPG concentrations correlated with neopterin ( r s = 0.494 , p = 0 . 027 ), but not with DAS28. OPG concentrations and disease activity scores declined during anti-TNF-treatment (both p < 0 . 02 ). Patients who achieved remission ( n = 7 ) or showed a good response according to EULAR criteria ( n = 13 ) presented with initially higher baseline OPG levels, which subsequently decreased significantly during treatment ( p = 0 . 018 for remission, p = 0 . 011 for good response). Conclusions. Adalimumab therapy was effective in modifying disease activity and reducing proinflammatory and bone remodelling cascades.
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