title: The Clinical Relevance of Anti-DFS70 Autoantibodies.
abstract: Despite all the progress in the establishment of specific autoantibody assays, screening for antinuclear antibodies (ANA) by indirect immunofluorescence on HEp-2 cells for quality-oriented laboratory diagnosis of ANA associated rheumatic diseases (AARD) remains indispensable but is not without limitations. Recent data on the relevance of the dense fine speckled (DFS) pattern and anti-DFS70 antibodies disclosed novel possibilities to optimize the serological stepwise diagnostics of AARD. The DFS pattern on HEp-2 cells is well differentiated from the classic "homogeneous" ANA pattern associated with dsDNA antibodies. This is the most frequent pattern in high titer ANA-positive healthy persons. The most characteristic ANA specificity associated with DFS pattern is the anti-DFS70 antibody (synonym LEDGF antibody). The prevalence of anti-DFS70 antibodies in AARD patients is significantly lower compared with the prevalence in ANA-positive healthy persons. There is a negative association between anti-DFS70 antibodies and AARD, especially if no concomitant AARD-specific autoantibodies are found. Isolated anti-DFS70 antibodies are detectable in less than 1 % of AARD but are detectable in 2-22 % of healthy persons. In the presence of an isolated anti-DFS70 antibody, the posttest probability for AARD is reduced significantly. The significance of anti-DFS70 antibodies as a criterion that helps to exclude AARD is also confirmed by follow-up studies on anti-DFS70 antibodies of positive, healthy individuals, who did not develop any AARD during a 4 year observation period. Consequently, anti-DFS70 antibodies are valuable novel biomarkers for better interpretation of positive ANA in cases of negative AARD-associated autoantibodies and should be integrated in modified test algorithms to avoid unnecessary referrals and examinations of ANA-positive persons.
authors.affiliation: Institute of Immunology, Medical Faculty "Carl Gustav Carus" of the Technical University of Dresden, Fetscherstrasse 74, 01307, Dresden, Germany. karsten.conrad@tu-dresden.de.
authors.forename: Karsten
authors.identifier: http://orcid.org/0000-0001-7581-6117
authors.initials: K
authors.lastname: Conrad
authors.affiliation: Institute of Immunology, Medical Faculty "Carl Gustav Carus" of the Technical University of Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Röber
authors.affiliation: Division of Rheumatology, Immuno-Rheumatology Laboratory, Escola Paulista de Medicina, Universidade Federal de Sâo Paolo, Sâo Paulo, Brazil.|Immunology Division, Fleury Laboratories, Sâo Paulo, Brazil.
authors.forename: Luis E C
authors.initials: LE
authors.lastname: Andrade
authors.affiliation: Research and Development, Inova Diagnostics, Inc., San Diego, CA, 92131, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mahler
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D000974:Antibodies, Antinuclear / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000276:immunology; D015415:Biomarkers / Q000032:analysis*; D006801:Humans; D014157:Transcription Factors / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; C504649:PSIP1 protein, human; D014157:Transcription Factors
keywords: ANA-associated rheumatic diseases; Anti-DFS70 antibodies; Antinuclear antibodies; Diagnostics