Current Concepts and Future Directions for the Assessment of Autoantibodies to Cellular Antigens Referred to as Anti-Nuclear Antibodies

Mähler, Michael; Meroni, Pier Luigi; Bossuyt, Xavier; Fritzler, Marvin J.

doi:10.1155/2014/315179

Cited by 159 publications

(178 citation statements)

References 145 publications

(176 reference statements)

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“…Antinuclear antibodies (ANA) are involved in the diagnosis of systemic sclerosis (SSc), being present in 90% of the patients 1,2,3 . In the majority of ANA-positive patients with SSc, a single SSc-specific autoantibody can be detected, i.e.…”

Section: To the Editormentioning

confidence: 99%

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Seroconversion from Anti-Th/To to Anticentromere Antibodies in a Patient with Systemic Sclerosis

2017

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Section: To the Editormentioning

confidence: 99%

“…In the majority of ANA-positive patients with SSc, a single SSc-specific autoantibody can be detected, i.e. antibodies to centromere protein B (CENP-B) 4 , topoisomerase I 5 , RNA Pol-III 3 , and Th/To 1,2,3,6,7 . These 4 major autoantibodies are typically mutually exclusive.…”

Section: To the Editormentioning

confidence: 99%

Seroconversion from Anti-Th/To to Anticentromere Antibodies in a Patient with Systemic Sclerosis

2017

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“…Although the IIF assay on HEp-2 cells has been replaced in some laboratories by ELISAs or multiplex assays using addressable laser beads, the IIF on Hep-2 substrate remains the "gold standard" for ANA screening as per American College of Rheumatology (ACR) recommendations 13 . These recommendations are based on the idea that the HEp-2 cell substrate comprises an "antigenic array" presenting >100 autoantibody targets whereas multiplex screening assays are usually more limited in autoantibody target composition 14 .…”

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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“…Fourth, diagnostic algorithms need to be adjusted to the clinical and laboratory setting considering the referral pattern, the sample testing volume, and health economic aspects. 15 …”

Section: Future Perspectivesmentioning

confidence: 99%

Anti-Nuclear antibodies: Current concepts and future direction for diagnosing connective tissue disease

Gautam¹

2015

J Pathol Nep

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Identification of antinuclear antibodies has been used for the diagnosis of connective tissue diseases for more than fifty years. Indirect immunofluorescence on human epithelial (HEp-2) cells is considered the gold standard screening method for the detection of antinuclear autoantibodies. As the demand of ANA testing increased, the need for automation and standardization has also come forth. A high level of false positive and false negative cases is seen in various populations making it difficult to take clinical decisions. Newer technologies were introduced for the antibody detection to ensure high sensitivity and specificity. This article intends to provide an overview of the concepts on ANA testing, the different diagnostic methods available, the various patterns and clinical utility, the clinical guidelines to be followed, the drawbacks and what lies ahead in the future of ANA testing.

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Current Concepts and Future Directions for the Assessment of Autoantibodies to Cellular Antigens Referred to as Anti-Nuclear Antibodies

Cited by 159 publications

References 145 publications

Seroconversion from Anti-Th/To to Anticentromere Antibodies in a Patient with Systemic Sclerosis

Seroconversion from Anti-Th/To to Anticentromere Antibodies in a Patient with Systemic Sclerosis

The history and recent advancements in antinuclear antibody testing

Anti-Nuclear antibodies: Current concepts and future direction for diagnosing connective tissue disease

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