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.