Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014–2015

Chan, Edward K. L.; Damoiseaux, Jan; Carballo, Orlando Gabriel; Conrad, Karsten; Cruvinel, Wilson de Melo; Francescantônio, Paulo Luiz Carvalho; Fritzler, Marvin J.; Torre, Ignacio García-De La; Herold, Manfred; Mimori, Tsuneyo; Satoh, Minoru; Mühlen, Carlos Alberto von; Andrade, Luís Eduardo Coelho

doi:10.3389/fimmu.2015.00412

Cited by 303 publications

(332 citation statements)

References 53 publications

(59 reference statements)

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“…A variety of methods are currently available for ANA testing in the clinical laboratory (2,5,6). The immunofluorescence assay (IFA) was the first method used for routine clinical ANA testing (7). This method is still used by a large number of laboratories, with most performed on an HEp-2 cellular substrate.…”

Section: Impact Statementmentioning

confidence: 99%

Utility of Antinuclear Antibody Screening by Various Methods in a Clinical Laboratory Patient Cohort

Duan

Peters

Ettore

et al. 2016

The Journal of Applied Laboratory Medicine

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Background Antinuclear antibody (ANA)5 testing is routinely performed during evaluation of patients with a suspected connective tissue disease (CTD), yet the question of which method is most appropriate remains controversial. The purpose of this study was to evaluate the clinical utility of ANA testing by an enzyme immunoassay (EIA), an immunofluorescence assay (IFA), and a multiplex immunoassay (MIA) in a routine laboratory population. Methods Samples (n = 1000) were collected from specimens submitted for ANA testing by EIA (Bio-Rad). All samples were subsequently analyzed by IFA (Zeus) and MIA (Bio-Rad). The sample cohort was weighted to represent the routine testing population. Diagnostic information was obtained by chart review. Results For the diagnosis of a CTD, ROC curve analysis demonstrated no significant differences between IFA (area under the curve 0.81) and EIA (0.84) (P = 0.25), with overlay of a single point for the MIA. When normalized to a specificity of approximately 90%, the sensitivities of the MIA, EIA, and IFA were 67%, 67%, and 56%, respectively. By varying the clinical cutoff, the IFA could achieve the highest sensitivity of 94%; however, the corresponding specificity was only 43%. In contrast, a strongly positive EIA had a specificity of 97%, although, at this cutoff, the sensitivity was only 40%. Conclusions Although the overall diagnostic performance of the IFA, EIA, and MIA were not statistically different, the clinical sensitivity and specificity varied dramatically based on the positive/negative cutoff. Knowledge about the performance characteristics of each method will significantly aid in the interpretation of ANA testing.

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Section: Impact Statementmentioning

confidence: 99%

Utility of Antinuclear Antibody Screening by Various Methods in a Clinical Laboratory Patient Cohort

Duan

Peters

Ettore

et al. 2016

The Journal of Applied Laboratory Medicine

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“…While the immunological mechanisms underlying these interactions are poorly understood, the presence of ANAs generally represents abnormal responses to self-antigens, a key feature of autoimmunity. In routine clinical laboratory evaluations, ANAs are generally categorized based on the recognition of homogeneous, speckled, centromere, and nucleolar patterns (1,2,(15)(16)(17). While ANAs are used as part of diagnoses for some SARDs (e.g., SLE, MCTD, and SjS), their presence may serve as an important diagnostic support for others (SSc, IIMs, secondary SjS, and juvenile arthritis).…”

Section: Indications For Antinuclear Antibody Testingmentioning

confidence: 99%

“…The use of HEp-2 cells, of human larynx epithelioma origin, provided increased sensitivities for detecting ANAs, probably due to their ability to divide rapidly in vitro as well as the presence of large nuclei, which allowed optimal detection of patterns associated with specific autoantibodies in SARDs (4,9,10). Although the ANA IFA method continued to be plagued by a number of analytical and diagnostic challenges, increasing recognition of the use of autoantibodies to diagnose and to further stratify SARDs, as well as efforts to harmonize the nomenclatures for testing and reporting, makes this a powerful screening tool (1,(11)(12)(13)(14)(15)(16)(17). Thus, testing for ANAs or ANA-specific autoantibodies has been incorporated in a few guidelines on diagnostic criteria.…”

mentioning

confidence: 99%

Recent Approaches To Optimize Laboratory Assessment of Antinuclear Antibodies

Tebo

2017

Clin Vaccine Immunol

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The presence of antinuclear antibodies (ANAs) is a hallmark of a number of systemic autoimmune rheumatic diseases, and testing is usually performed as part of the initial diagnostic workup when suspicion of an underlying autoimmune disorder is high. The indirect immunofluorescence antibody (IFA) technique is the preferred method for detecting ANAs, as it demonstrates binding to specific intracellular structures within the cells, resulting in a number of staining patterns that are usually categorized based on the cellular components recognized and the degree of binding, as reflected by the fluorescence intensity or titer. As a screening tool, the ANA patterns can guide confirmatory testing useful in elucidating a specific clinical diagnosis or prognosis. However, routine use of ANA IFA testing as a global screening test is hampered by its labor-intensiveness, subjectivity, and limited diagnostic specificity, among other factors. This review focuses on current efforts to standardize the nomenclature of ANA patterns and on alternative methods for ANA determination, as well as on recent advances in image-based computer algorithms to automate IFA testing in clinical laboratories.

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“…To promote laboratory quality control of ANA and other autoantibody testing, the Autoantibody Standardization Committee has collaborated with the Centres for Disease Control and Prevention (CDC) and other agencies to provide autoantibody reference standards and provides 17 reference standards available free of charge to all qualified clinical or commercial laboratories and research investigators 15 .…”

Section: Ana Testing-iif On Hep-2mentioning

confidence: 99%

The history and recent advancements in antinuclear antibody testing

Moschou¹,

Pipi²,

Tsirogianni³

2017

JRPMS

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In 1948, Malcolm Hargraves, Helen Richmond, and Robert Morton during evaluation of bone marrow examinations at the Mayo Clinic (Minnesota, USA) observed exclusively in patients with systemic lupus erythematosus (SLE) the presence of abnormal cells with specific morphology (the nucleus is phagocytosed by mature leucocytes) and introduced the term "LE cell" 1 . Although LE cells are usually found in the bone borrow of these patients, it has been shown that after a period of incubation they can be formed in buffy coats of peripheral blood 2 indicating that the LE phenomenon is rather a secondary response to a blood circulating factor and not a developmental cellular defect.One year later, two research laboratories independently confirmed the inducible nature of LE phenomenon 3 . Incubation of bone marrow cells from healthy subject with plasma from SLE patients lead to the formation of LE cells. It took almost a decade and a series of ingenious research to discover that the phenomenon LE cells are autoantibodies that bind to nuclear elements. The molecular nature of the LE factor was determined when it was discovered that this factor lies in the gamma globulin fraction 4 . The nuclear specificity has been shown later by at least two different research groups at the same time. Holborow et al, showed that in all tissues examined (skin, heart muscle, kidney, thyroid and spleen) exposure of the section to LE cells positive sera resulted in marked specific fluorescence of the nuclei on subsequent staining with the anti-globulin conjugate 5 .In the same year, Holman and Kunkel published a seminal work in Science where they show that the LE serum factor possesses affinity for cell nuclei and nucleoproteins 6 . One year later, Friou and colleagues introduced an indirect immunofluorescence (IIF) assay with end-point titres for the detection of anti-nuclear antibodies 7,8 (ANA). Subsequently, three distinct classic patterns (homogeneous, speckled and nucleolar) of ANA fluorescence were described by Swanson Beck during the staining of rat liver sections with patients' serum 9 , introducing the importance of ANA pattern in clinical practice. Since then significant progress has been made on the identification of ANA specificity in SLE and other systemic autoimmune rheumatic diseases, including Rheumatoid Arthritis (RA), Sjögren's Syndrome (SjS), Systemic Sclerosis (SSc), Mixed Connective Tissue Disease (MCTD), and Idiopathic Inflammatory Myopathies (IIM). AbstractThe antinuclear antibody (ANA) testing is an indispensable diagnostic tool for the management of systemic autoimmune rheumatic diseases (SARD). From the initial discovery of ANA identification until today there has been considerable technical progress in ANA testing and standardisation which has allow the development of commercial ANA assay kits that are widespread used in clinical and research practice. In this mini-review we explore the history and recent advancements in ANA testing and provide guidelines to the laboratory interpretation and clinical assessment of ANA...

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Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014–2015

Cited by 303 publications

References 53 publications

Utility of Antinuclear Antibody Screening by Various Methods in a Clinical Laboratory Patient Cohort

Utility of Antinuclear Antibody Screening by Various Methods in a Clinical Laboratory Patient Cohort

Recent Approaches To Optimize Laboratory Assessment of Antinuclear Antibodies

The history and recent advancements in antinuclear antibody testing

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