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Xavier Bossuyt - One of the best experts on this subject based on the ideXlab platform.

  • titre specific positive predictive value of Antinuclear Antibody patterns
    2021
    Co-Authors: Jeanbaptiste Vulsteke, Rene Westhovens, Daniel Engelbert Blockmans, Lieve Van Hoovels, Philippe Willems, Bert Vander Cruyssen, Steven Vanderschueren, Ellen De Langhe, Xavier Bossuyt
    Abstract:

    Damoiseaux et al recently presented the ICAP perspective on the clinical relevance of Antinuclear Antibody (ANA) patterns.1 The authors acknowledge that in addition to the Antibody pattern, the Antibody titre (level) is clinically important as well. Indeed, the probability of identifying anti‐dsDNA and antibodies to extractable nuclear antigens increases with increasing ANA titres.2 Overall, the higher the Antibody level, the higher the probability of an ANA-associated systemic rheumatic disease (AASRD).3–5 There are only few studies that demonstrate the association of a particular ANA pattern and titre with AASRDs or other ANA-associated diseases. We previously studied the titre-dependent clinical association of rare ANA patterns.6 We here demonstrate how the positive predictive value (PPV) for an AASRD (including systemic lupus erythematosus (SLE), Sjogren’s syndrome (SjS), systemic sclerosis (SSc), idiopathic inflammatory myopathy (IIM), mixed connective tissue disease and undifferentiated connective tissue disease (UCTD)) depends on the combination of Antibody pattern and titre. We evaluated the pattern-specific and titre-specific association of ANA for AASRDs, cutaneous lupus erythematosus (CLE), autoimmune hepatitis (AIH) and juvenile idiopathic arthritis (JIA) on (1) 9851 unique consecutive patients tested for ANA by HEp-2000 (ImmunoConcepts) (for description of the population, see Willems et al 5) in a university hospital setting (University Hospitals Leuven, Belgium) and on (2) 529 unique consecutive patients tested for ANA by automated indirect immunofluorescence (IFA) (NOVAView) on human epithelial (HEp-2) cells from INOVA in the rheumatology department of a secondary hospital setting (OLV hospital Aalst, Belgium). The patients have been clinically defined by the respective classification criteria for each AASRD (as described in Willems et al 5) or by expert clinical diagnosis (for patients who did not fulfil the classification criteria). The analysis was performed for the most prevalent ANA patterns (speckled, homogeneous, nucleolar and centromere) and only monospecific nuclear patterns were included, …

  • value added reporting of Antinuclear Antibody testing by automated indirect immunofluorescence analysis
    2014
    Co-Authors: Sofie Schouwers, Myriam Bonnet, Patrick Verschueren, Rene Westhovens, Daniel Engelbert Blockmans, Godelieve Marien, Xavier Bossuyt
    Abstract:

    Background Automated systems for Antinuclear Antibody analysis are being introduced. The aim was to evaluate whether automated quantitative reading of fluorescence intensity is clinically relevant and allows for value-added reporting of test results. Methods Consecutive samples (n=260) were used to correlate fluorescence intensity with end-point titer. Moreover, 434 samples from controls (150 healthy blood donors, 150 chronic fatigue syndrome, and 134 diseased controls) and 252 samples (obtained at diagnosis) from patients with systemic rheumatic diseases were screened for Antinuclear antibodies (1:80) on HEp-2 cells using NOVA View, and likelihood ratios were calculated for fluorescence intensity result intervals. Results There was a significant correlation between end-point titer and fluorescence intensity. Likelihood ratios for a systemic rheumatic disease increased with increasing fluorescence intensity. The likelihood ratio for a systemic rheumatic disease was 0.06, 0.18, 0.51, 5.3, and 37.5 for a fluorescence intensity of ≤66, 67-150, 151-300, 301-1000, >1000, respectively. A range of 31%-37% of the patients with Sjogren's syndrome, systemic sclerosis or systemic lupus erythematosus had fluorescence intensities >1000. Conclusions Estimation of fluorescence intensity by automated Antinuclear Antibody analysis offers clinically useful information. Likelihood ratios based on fluorescence intensity test result intervals aid with the interpretation of automated Antinuclear Antibody analysis and allow value-added reporting.

  • prevalence and clinical significance of rare Antinuclear Antibody patterns
    2013
    Co-Authors: Pieter Vermeersch, Xavier Bossuyt
    Abstract:

    While some of the more frequent Antinuclear (auto)antibodies (ANA) patterns such as homogenous nuclear staining have been extensively studied, the prevalence and clinical significance of rare Antinuclear Antibody patterns are not well understood. For the purpose of this review, we defined rare patterns as patterns occurring in less than 1% of patients that test positive on indirect immunofluorescence. The prevalence of different ANA patterns was determined in 68,128 consecutive patients who attended the outpatient clinic or were hospitalized at the University Hospitals Leuven over a 14-year period (1998-2011). To avoid bias, we only included the first sample for each patient and patients who tested positive in the period 1980-1997 were excluded. There were 9268 patients who tested positive for ANA. With the exception of the clinical association of anti-multiple nuclear dots (at higher titers) and anti-nuclear envelope autoantibodies with autoimmune liver disease, there was no good clinical association of rare ANA patterns with the diagnosis of auto-immune disorders. The most important non-autoimmune cause of rare ANA patterns was carcinoma, particularly in patients with rare cell-cycle related ANAs.

  • current practices in Antinuclear Antibody testing results from the belgian external quality assessment scheme
    2009
    Co-Authors: Marjan Van Blerk, Xavier Bossuyt, Christel Van Campenhout, Jean Duchateau, Rene Humbel, Genevieve Servais, Jeanpaul Tomasi, Adelin Albert, Wim W Coucke, Jeanclaude Libeer
    Abstract:

    Background This study aimed to assess the state-of-the-art of Antinuclear Antibody (ANA) testing as practiced in the Belgian and Luxembourg laboratories, using the results obtained in the Belgian National External Quality Assessment Scheme from 2000 to 2005. Methods During this period, nine samples with different specificities were sent for analysis. Participants were surveyed for methodology used and were asked to report staining pattern and titer of ANAs. In 2002, an attempt was made to improve the comparability of quantitative ANA results by the provision of a commercial reference material and to relate observed differences to methodology. Results With one exception, all participants employed a microscope-based indirect immunofluorescence assay with human epithelial cell line 2 cells. Most laboratories were accurate in describing the pattern. The percentage of unacceptable answers was greater for samples with borderline levels of Antibody and for samples showing a cytoplasmic pattern. An improvement in the detection of anticentromere antibodies was observed. For all samples, a wide range of titers was reported. The provision of the secondary reference preparation led to improved inter-laboratory concordance. Comparison of methodology variables revealed a correlation between unstandardized titers and the power of the lamp of the microscope and the use of a dark room. Conclusions The EQAS results presented in this work provide valuable insights into the state of the art of ANA testing as practiced in the Belgian and Luxembourg Laboratories and illustrate the important value of a national EQAS for ANA testing as a tool to improve performance and interlaboratory comparability of laboratory results.

David S Pisetsky - One of the best experts on this subject based on the ideXlab platform.

Brad H Rovin - One of the best experts on this subject based on the ideXlab platform.

Marvin J Fritzler - One of the best experts on this subject based on the ideXlab platform.

  • the Antinuclear Antibody test in the diagnosis of antisynthetase syndrome and other autoimmune myopathies
    2018
    Co-Authors: Marvin J Fritzler, May Y Choi, Michael Mahler
    Abstract:

    Autoantibodies directed to intracellular macromolecules are a characteristic feature of Antinuclear Antibody (ANA)-associated rheumatic diseases (AARD) such as systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, Sjogren syndrome, and autoimmune inflammatory myopathies (AIM). Some of these autoantibodies are highly specific for the individual AARD and hence are termed disease-specific antibodies, and some are included in the classification and/or diagnostic criteria for these diseases1. In this context, the report by Aggarwal, et al in The Journal 2 is timely and provides insight into the value of screening for anticytoplasmic antibodies (anti-CytAb) as an adjunct to the diagnosis of the antisynthetase syndrome, a subset of AIM3. In their retrospective analysis of 202 patients with antisynthetase syndrome, the anti-CytAb test performed better than the conventional ANA indirect immunofluorescence (IIF) test in identifying antisynthetase syndrome as evidenced by higher sensitivity (72% vs 50%) and specificity (89% vs 6%). Consequently, they indicate that a negative ANA test does not rule out the diagnosis of antisynthetase syndrome or AIM. That a negative ANA does not indicate autoAntibody negativity in antisynthetase syndrome or AIM is an important message that may be misunderstood by clinicians. Despite remarkable efforts to standardize ANA nomenclature by the International Consensus on ANA Pattern (ICAP) committee4,5, there is considerable confusion about the term ANA . The efforts of the ICAP were recognized by Aggarwal, et al , but they, as well as some diagnostic laboratories and clinicians, continue to interpret and understand the definition of ANA in a strict sense, meaning only autoantibodies that react with nuclear targets are properly regarded as ANA. The spectrum of autoAntibody targets in the nucleus is wide and includes components of the nuclear envelope, nuclear pore complex, nuclear matrix, nucleoplasm, chromatin and chromosomes, nucleolus, and promyelocyte leukemia/coiled bodies … Address correspondence to Dr. M.J. Fritzler, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 4N1, Canada. E-mail: fritzler{at}ucalgary.ca

  • recognition of the dense fine speckled dfs pattern remains challenging results from an international internet based survey
    2016
    Co-Authors: Chelsea Bentow, Marvin J Fritzler, Eckart Mummert, Michael Mahler
    Abstract:

    Purpose The dense fine speckled (DFS) pattern as detected by indirect immunofluorescence (IIF) on HEp-2 cells has been associated with several inflammatory diseases but is most commonly observed in individuals that do not have an Antinuclear Antibody (ANA)-associated rheumatic disease and even in apparently healthy individuals. Consequently, the accurate identification and correct reporting of this IIF pattern is of utmost importance and accordingly has been recognized by several international study groups for the detection of ANA. Furthermore, the DFS IIF pattern has recently been recommended as a competency level recognition pattern by the International Consensus on Antinuclear Antibody (ANA) Pattern (ICAP, http://www.anapatterns.org/) Committee. The objective of this study was to use an internet-based survey to assess how accurately the DFS IIF pattern was recognized by experienced technologists.

  • report of the first international consensus on standardized nomenclature of Antinuclear Antibody hep 2 cell patterns 2014 2015
    2015
    Co-Authors: Edward K L Chan, Ignacio Garciade La Torre, Jan Damoiseaux, Orlando Gabriel Carballo, Karsten Conrad, Wilson De Melo Cruvinel, Paulo Luiz Carvalho Francescantonio, Marvin J Fritzler, Manfred Herold, Tsuneyo Mimori
    Abstract:

    During the 12th International Workshop on Autoantibodies and Autoimmunity held in Sao Paulo, Brazil, on August 28, 2014, a full day session was devoted to establishing a consensus on the nomenclature of staining patterns observed in the Antinuclear Antibody (ANA) indirect immunofluorescence test on HEp-2 cells. The current report summarizes the collective agreements with input from the host Brazilian and international communities that represented research, clinical, and diagnostic service laboratories. Patterns are categorized in three major groups (nuclear, cytoplasmic, and mitotic patterns) and each pattern has been defined and described in detail. The consensus nomenclature and representative patterns are made available online at the international consensus on Antinuclear Antibody pattern (ICAP) website (www.ANApatterns.org). To facilitate continuous improvement and input, specific comments on ICAP are encouraged and these will be discussed in subsequent ICAP meetings. The ultimate goal with the establishment of the ICAP is to promote harmonization and understanding of autoAntibody test nomenclature, as well as interpretation guidelines for ANA testing, thereby optimizing usage in patient care.

  • the Antinuclear Antibody test last or lasting gasp
    2011
    Co-Authors: Marvin J Fritzler
    Abstract:

    Autoantibodies have been regarded as a serologic hallmark of systemic autoimmune rheumatic diseases (ARDs) for more than half a century. Two years following the landmark discovery of the lupus erythematosus (LE) cell and the LE cell phenomenon by Hargraves and colleagues at the Mayo Clinic in 1948 (1), Coons and Kaplan described indirect immunofluorescence (IIF) as a useful approach to the detection of serum autoantibodies directed against intracellular antigens (2). This led to IIF applications designed to detect Antinuclear antibodies (ANAs) as a key approach to the laboratory diagnosis of systemic lupus erythematosus (SLE) and eventually other systemic ARDs (3). After more than 50 years of widespread use, the ANA test and other IIF applications have enjoyed a favored position in diagnostic medicine, although they have been plagued by limitations and are now being challenged by newer diagnostic platforms and technologies (4). The advent and acceptance of the newer technologies has also been predicated on the appreciation that the ANA IIF test is not well suited to high-volume and high-throughput laboratories where the containment of medical health care costs has been a determining factor. Nevertheless, it has been recognized that many of these high-throughput technologies have limitations, most notably falsenegative results, in the detection of ANAs (5). To address these issues and concerns, the American College of Rheumatology (ACR) convened a committee to undertake an analysis and provide recommendations with respect to ANA testing as an approach to diagnosing systemic ARDs. In May 2010, a summary of the committee’s findings and recommendations was published; among these was the recommendation that the ANA IIF test using cell substrates should be considered the “gold standard” assay to screen for autoantibodies in sera from patients with systemic ARDs (5). For several decades, it has been well known that the ANA IIF test is compromised by the lack of universal standardization and by false-positive tests that lead (in some clinicians’ opinions) to “unnecessary” referrals or even to inappropriate diagnoses. An interesting case in point are autoantibodies that produce a staining pattern referred to as nuclear dense fine speckled, and in this issue of Arthritis & Rheumatism, Mariz and colleagues elaborate on the nuclear dense fine speckled pattern and provide timely and provocative observations about its usefulness as a screening test for systemic ARDs (6). However, unlike the case with other ANAs, Mariz et al suggest that the detection of the nuclear dense fine speckled staining pattern can be used as a biomarker to rule out the diagnosis of SLE and/or other systemic ARDs. Two key points need to be made: first, it should not be concluded that all sera demonstrating the nuclear dense fine speckled staining pattern are from healthy individuals; second, before the observations and conclusions reached by Mariz and colleagues can be widely accepted and applied in clinics, a number of issues should be addressed.

Edward K L Chan - One of the best experts on this subject based on the ideXlab platform.

  • report of the first international consensus on standardized nomenclature of Antinuclear Antibody hep 2 cell patterns 2014 2015
    2015
    Co-Authors: Edward K L Chan, Ignacio Garciade La Torre, Jan Damoiseaux, Orlando Gabriel Carballo, Karsten Conrad, Wilson De Melo Cruvinel, Paulo Luiz Carvalho Francescantonio, Marvin J Fritzler, Manfred Herold, Tsuneyo Mimori
    Abstract:

    During the 12th International Workshop on Autoantibodies and Autoimmunity held in Sao Paulo, Brazil, on August 28, 2014, a full day session was devoted to establishing a consensus on the nomenclature of staining patterns observed in the Antinuclear Antibody (ANA) indirect immunofluorescence test on HEp-2 cells. The current report summarizes the collective agreements with input from the host Brazilian and international communities that represented research, clinical, and diagnostic service laboratories. Patterns are categorized in three major groups (nuclear, cytoplasmic, and mitotic patterns) and each pattern has been defined and described in detail. The consensus nomenclature and representative patterns are made available online at the international consensus on Antinuclear Antibody pattern (ICAP) website (www.ANApatterns.org). To facilitate continuous improvement and input, specific comments on ICAP are encouraged and these will be discussed in subsequent ICAP meetings. The ultimate goal with the establishment of the ICAP is to promote harmonization and understanding of autoAntibody test nomenclature, as well as interpretation guidelines for ANA testing, thereby optimizing usage in patient care.

  • Antinuclear Antibody test when to order
    2013
    Co-Authors: Pier Luigi Meroni, Edward K L Chan, Angela Tincani, Ignacio Garciade La Torre, Luis Eduardo Coelho Andrade
    Abstract:

    The article discourages the test even in cases withlimited clinical justification. We contend that such a sugges-tion is ill advised because nonrheumatologists would runthe risk of missing potential autoimmune patients. The lowcost of a single Antinuclear Antibody test and the direct/indirect costs ofa delayed diagnosis ofAntinuclear Antibodyeassociated autoimmune diseases generate a cost/benefitratiofavoring the test. A careful analysis of the data

  • Clinical interpretation of Antinuclear Antibody tests in systemic rheumatic diseases
    2009
    Co-Authors: Minoru Satoh, Monica Vázquez-del Mercado, Edward K L Chan
    Abstract:

    AutoAntibody tests have been used extensively in diagnosis and follow-up of patients in rheumatology clinics. Immunofluorescent Antinuclear Antibody test using HEp-2 cells is still considered the gold standard for screening of autoantibodies, and most of specific autoantibodies are currently tested by ELISA as a next step. Among the many autoAntibody specificities described, some have been established as clinically useful diagnostic markers and are included in the classification criteria of diseases. Despite a long history of routine tests and attempts to standardize such assays, there are still limitations and problems that clinicians need to be aware of. Clinicians should be able to use autoAntibody tests more efficiently and effectively with a basic knowledge on the significance of and potential problems in autoAntibody tests.