DFS70 antibodies – biomarkers for the exclusion of ANA-associated autoimmune rheumatic diseases

Abstract Despite 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. Research results on the relevance of the dense fine speckled (DFS) pattern and 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. In DFS pattern positive sera the most important detectable ANA specificity is the DFS70 antibody (synonym LEDGF antibody). This antibody is also the most frequent ANA specificity in ANA positive healthy persons. The prevalence of DFS70 antibodies in AARD patients is significantly lower compared with the prevalence in ANA-positive healthy individuals. There is a negative association between DFS70 antibodies and AARD, especially if no concomitant AARD-specific autoantibodies are found. Isolated DFS70 antibodies are detectable in <1% of AARD, but are detectable in 5%–11% of healthy individuals. In the presence of an isolated DFS70 antibody, the posttest probability for AARD is reduced significantly. DFS70 antibodies are valuable novel biomarkers for the improved interpretation of positive ANA but without detectable AARD associated autoantibodies and should be integrated in modified test algorithms to avoid unnecessary referrals and examinations of ANA-positive subjects.