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Journal of Immunology Research
Volume 2014, Article ID 315179, 18 pages
Review Article

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

1INOVA Diagnostics, Inc., 9900 Old Grove Road, San Diego, CA 92131-1638, USA
2Rheumatology & Experimental Laboratory of Immuno-rheumatology, University of Milan, Istituto Auxologico Italiano, Via G. Zucchi 18, 20095 Cusano Milanino, Milan, Italy
3Department of Microbiology and Immunology, Laboratory Medicine, University Hospitals Leuven, KU Leuven, Belgium
4Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1

Received 13 December 2013; Accepted 27 January 2014; Published 27 April 2014

Academic Editor: Ghislain Opdenakker

Copyright © 2014 Michael Mahler et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The detection of autoantibodies that target intracellular antigens, commonly termed anti-nuclear antibodies (ANA), is a serological hallmark in the diagnosis of systemic autoimmune rheumatic diseases (SARD). Different methods are available for detection of ANA and all bearing their own advantages and limitations. Most laboratories use the indirect immunofluorescence (IIF) assay based on HEp-2 cell substrates. Due to the subjectivity of this diagnostic platform, automated digital reading systems have been developed during the last decade. In addition, solid phase immunoassays using well characterized antigens have gained widespread adoption in high throughput laboratories due to their ease of use and open automation. Despite all the advances in the field of ANA detection and its contribution to the diagnosis of SARD, significant challenges persist. This review provides a comprehensive overview of the current status on ANA testing including automated IIF reading systems and solid phase assays and suggests an approach to interpretation of results and discusses meeting the problems of assay standardization and other persistent challenges.