What is the clinical significance of a positive Antinuclear Antibody (ANA) test with a speckled pattern at a titer of 1:160, characterized by a dense fine speckled pattern, and the presence of DFS70 antibody in a patient?

From the Guidelines

The presence of DFS70 antibodies with a dense fine speckled pattern at a titer of 1:160 is generally considered a benign finding, with a low association with systemic autoimmune rheumatic diseases, as indicated in the study published in the Annals of the Rheumatic Diseases 1. This ANA test result shows a positive speckled pattern with a dense fine speckled (DFS) pattern, specifically identifying the presence of DFS70 antibodies.

• The study published in the Annals of the Rheumatic Diseases 1 provides a comprehensive overview of the different patterns and related antigens/diagnosis, including the dense fine speckled pattern associated with DFS70 antibodies.
• According to the study, the dense fine speckled pattern is less commonly recognized and is associated with DFS70/LEDGF-P75, which is often found in healthy subjects and other inflammatory conditions, rather than systemic autoimmune rheumatic diseases.
• The presence of DFS70 antibodies is generally reassuring, as they have a low association with systemic autoimmune rheumatic diseases like lupus or scleroderma, as noted in the study 1.
• No specific treatment is needed based solely on this finding, but if symptoms concerning for autoimmune disease are present, further evaluation with additional antibody tests would be appropriate.
• The significance of this pattern is that it helps distinguish between true autoimmune conditions and false positive ANA results, potentially avoiding unnecessary treatments or anxiety, as suggested by the study 1.
• Regular follow-up with a healthcare provider is recommended if new symptoms develop, but this specific antibody pattern is often considered a benign finding, as indicated in the study 1.

From the Research

ANA Positive Speckled Pattern and DFS70 Antibody

• The presence of a dense fine speckled (DFS) pattern on HEp-2 cells is often associated with anti-DFS70 specificity, as noted in studies 2, 3, 4, 5, 6.
• Anti-DFS70 positive patients rarely develop systemic autoimmune rheumatic disease (SARD), especially in the absence of clinical evidence or additional anti-extractable nuclear antigen (ENA) antibodies 2, 3, 4, 5.
• The prevalence of anti-DFS70 antibodies in SARD patients is significantly lower compared to the prevalence in ANA-positive healthy persons 3, 4, 5.
• Isolated anti-DFS70 antibodies are detectable in less than 1% of SARD patients but are detectable in 2-22% of healthy persons 3, 4, 5.

Clinical Relevance of Anti-DFS70 Antibodies

• The recognition of a DFS ANA pattern using a mitotic-rich HEp-2 substrate, followed by confirmation of anti-DFS70 specificity, should be a routine ANA testing service 2, 3, 4, 5.
• The presence of significant elevations of other ENAs may reflect SARD and warrants close clinical correlation and follow-up 2, 3, 4, 5.
• Anti-DFS70 antibodies are valuable novel biomarkers for better interpretation of positive ANA in cases of negative AARD-associated autoantibodies and should be integrated into modified test algorithms to avoid unnecessary referrals and examinations of ANA-positive persons 3, 4, 5, 6.

DFS70 Autoantibodies and Clinical Utility

• Screening for antinuclear antibodies (ANA) by indirect immunofluorescence (IIF) on HEp-2 cells is helpful for the diagnosis and classification of ANA-associated rheumatic diseases 5.
• The target antigen of the antibodies that cause the DFS pattern is a 70 kDa protein (DFS70), and commercial methods that detect antibodies to full-length or truncated DFS70 are available for use in clinical laboratories 5.
• Monospecific anti-DFS70 (i.e., in the absence of antibodies that are linked to ANA-associated rheumatic diseases) is rarely found in ANA-associated rheumatic diseases 5, 6.