title: Importance of the dense fine speckled pattern on HEp-2 cells and anti-DFS70 antibodies for the diagnosis of systemic autoimmune diseases.
abstract: The presence of anti-nuclear antibodies (ANA) is a hallmark of systemic autoimmune rheumatic diseases (SARD). The indirect immunofluorescence (IIF) assay on HEp-2 cells is a commonly used test for the detection of ANA and was recently recommended as the screening test of choice by a task force of the American College of Rheumatology. However, up to 20% of serum samples from healthy individuals (HI) have been reported to have a positive ANA test, the majority of which are directed to the dense fine speckles 70 (DFS70) antigen. Even more important, the DFS IIF pattern has been reported in 33% of ANA positive HI, but not in ANA positive SARD sera. Since the intended use of the ANA HEp-2 test is to aid in the diagnosis of SARD, the reporting of anti-DFS70 antibodies and their associated pattern (DFS) as a positive test, significantly reduces the specificity and the positive likelihood of the ANA test. This has significant implications for diagnostic algorithms involving the detection of ANA. We summarize the current knowledge of anti-DFS70 antibodies and their impact on ANA testing. We also suggest a test algorithm which considers the DFS pattern and the presence of anti-DFS70 antibodies. In addition, we describe a novel method based on immunoadsorption of anti-DFS70 antibodies, which increases the specificity of the ANA HEp-2 test for SARD and which has the potential to overcome a significant limitation of the ANA HEp-2 assay.
authors.affiliation: INOVA Diagnostics, INC. San Diego, CA 32131-1638, USA. mmahler@inovadx.com
authors.forename: Michael
authors.initials: M
authors.lastname: Mahler
authors.forename: John G
authors.initials: JG
authors.lastname: Hanly
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Fritzler
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000465:Algorithms; D000974:Antibodies, Antinuclear / Q000097:blood* / Q000276:immunology; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000276:immunology; D005189:False Positive Reactions; D019084:Fluorescent Antibody Technique, Indirect; D056945:Hep G2 Cells; D006801:Humans; D012680:Sensitivity and Specificity; D013194:Staining and Labeling; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000974:Antibodies, Antinuclear; C504649:PSIP1 protein, human; D014157:Transcription Factors