What does a strong positive DFS70 (Double Stranded DNA Fragment 70) result on an Antinuclear Antibody (ANA) blot imply?

Clinical Significance of Strong Positive DFS70 on ANA Blot

A strong positive DFS70 result on an ANA blot typically indicates a low probability of systemic autoimmune rheumatic disease (SARD) and may actually serve as a negative predictor for developing such conditions when found in isolation. 1

Understanding DFS70 Antibodies

• DFS70 (Dense Fine Speckled 70) antibodies produce a characteristic fine speckled pattern on ANA testing and are commonly found in ANA-positive healthy individuals 2
• These antibodies are directed against the DFS70/LEDGF protein and are present in 2-22% of healthy subjects while rarely found in patients with systemic autoimmune rheumatic diseases 1
• The prevalence of monospecific anti-DFS70 antibodies is significantly higher in healthy subjects than in patients with ANA-associated rheumatic diseases (10.9% vs. 1.9%) 2

Clinical Implications

• When isolated (without other detectable specific autoantibodies), anti-DFS70 is considered a negative predictor for the development of systemic autoimmune rheumatic diseases 1
• The presence of anti-DFS70 antibodies helps clarify positive ANA-IIF results, especially when the pretest probability for autoimmune disease is low 3
• Gender differences exist in DFS70 positivity: no concomitant autoantibodies were found in DFS70-positive males, while 51% of DFS70-positive females showed other serum autoantibodies 4

Recommended Follow-Up Testing

• Confirmation of DFS70 positivity should be performed using a specific assay such as immunoblotting, ELISA, or chemiluminescent immunoassay (CIA) 3
• Testing for specific extractable nuclear antigens (ENA) is recommended to rule out other autoimmune conditions, including anti-RNP, anti-SSA/Ro, anti-SSB/La, and anti-dsDNA 5
• When clinical suspicion for autoimmune disease remains despite DFS70 positivity, testing for disease-specific antibodies should be performed based on clinical presentation 5

Interpretation Guidelines

• Both the pattern and titer of ANA should be reported, with a screening dilution of 1:160 on conventional HEp-2 substrates often suitable for adult populations 5
• It is important to determine if the DFS70 antibodies are isolated (monospecific) or if they co-occur with other autoantibodies associated with specific autoimmune diseases 3
• The absence of AARD-associated autoantibodies and clinical symptoms contributes more to the exclusion of autoimmune disease than the mere presence of anti-DFS70 3

Common Pitfalls and Caveats

• Different laboratories may use different methods and cutoffs for ANA and DFS70 testing, affecting result interpretation 5
• The prevalence of anti-DFS70 antibodies varies depending on the care setting, with higher prevalence in primary care (21%) compared to secondary (6-12%) and tertiary care (8%) 3
• False positives can occur, so confirmation with a specific anti-DFS70 assay is recommended when this pattern is observed on routine ANA testing 2
• Low-titer positive results may be seen in healthy individuals and should be interpreted with caution 5

Clinical Context

• Anti-DFS70 reactivity in males may represent a useful biomarker predicting the absence of other autoantibodies 4
• In females with positive DFS70, further investigation is warranted to define the presence of concomitant disease-marker autoantibodies 4
• Some DFS70-positive sera may have antibodies that recognize antigens of the lens and cornea, though the clinical significance of this finding is unclear 6