Specificity of antinuclear autoantibodies recognizing the dense fine speckled nuclear pattern: Preferential targeting of DFS70/LEDGFp75 over its interacting partner MeCP2

- We used several approaches to accurately detect DFS70/LEDGFp75 antibodies in DFS sera.
- We established that DFS sera specifically target DFS70/LEDGFp75.
- MeCP2, the 70 kD partner of DFS70/LEDGFp75 is not targeted by DFS sera.
- DFS70/LEDGFp75 itself appears to be the inciting antigen of anti-DFS autoantibodies.
- The monospecificity of anti-DFS autoantibodies gives insights into their significance.

Human antinuclear autoantibodies (ANAs) targeting the dense fine speckled (DFS) nuclear protein DFS70, commonly known as lens epithelium derived growth factor p75 (LEDGFp75), present a clinical puzzle since their significance remains elusive. While their frequencies are low in ANA-positive autoimmune rheumatic diseases, they are relatively elevated in clinical laboratory referrals, diverse inflammatory conditions, and 'apparently' healthy individuals. We reported previously that DFS70/LEDGFp75 is an autoantigen in prostate cancer that closely interacts with another 70 kD DFS nuclear protein, methyl CpG binding protein 2 (MeCP2). This led us to investigate if anti-DFS sera exclusively target DFS70/LEDGFp75 or also recognize MeCP2. Using several complementary autoantibody detection platforms and cellular/molecular approaches we evaluated 65 human sera producing anti-DFS autoantibodies. Our results show that these antibodies are highly specific for DFS70/LEDGFp75 and do not target MeCP2. Establishing the specificity of anti-DFS autoantibodies has implications for increasing our understanding of their biological significance and clinical utility.