DFS 70 – Exploring A New Paradigm
Systemic lupus erythematosus (SLE) is a multisystem chronic autoimmune inflammatory disease affecting almost any organ system, its presentation and course can be highly variable. The diagnosis of SLE is based on a combination of clinical findings and laboratory evidence. Clinicians can recognize SLE and can classify this complex disease based on pattern of target-organ manifestations along with laboratory diagnosis. SLE gradually gets worse over time, and damage to the major organs of the body can be life-threatening. The presence of anti-nuclear antibodies (ANAs) forms key diagnostic and differentiating criteria in the diagnosis of systemic rheumatic diseases (SARD).
ANA occurs in a wide variety of autoimmune diseases, including SARD SLE, primary biliary cirrhosis, mixed connective tissue disorders, Sjogren’s syndrome (SSc), and polymyositis. ANA thus serves as a useful biomarker in the differential diagnosis of SARD. ANA present different patterns depending on the staining of the cell nucleus in the laboratory: homogeneous, speckled, nucleolar, peripheral etc. These patterns, however are not specific for any illness, certain autoimmune diseases can more frequently be associated with one pattern or another.
According to ACR guidelines, indirect immunofluorescence technique using human epithelial cells (HEp2) is the recommended gold standard technique in the screening of ANA as this substrate allows the screening of more than 100 autoantigens. Autoantibodies targeting the nuclear autoantigen DFS 70 have attracted much attention due to their relatively common occurrence in patient sera referred for ANA testing. Dense fine speckled (DFS-AC 2) is a nuclear target antigen according to the reactivity of the autoantibody with a 70 kDa protein in western blot.
Protein sequence database have shown that DFS 70 is identical to the protein designated as transcriptional coactivator p75 (LEDGF – lens epithelium derived growth factor).
The typical nuclear dense fine speckled (DFS) pattern on HEp 2 cells is recognized as uniformly distributed fine granules throughout the interphase nucleus and on metaphase chromatin, and it is considered as a standard pattern according to the international consensus on ANA patterns (ICAP). Identification of DFS 70 by IIF is challenging. There are difficulties in differentiation of DFS 70 from the homogeneous pattern. However, the recognition of DFS 70 is vital as it is considered as a strong evidence against diagnosis of systemic autoimmune rheumatic diseases.
The clinical significance of anti DFS 70 is unclear due to its common occurrence. They lack disease specificity and can be found in apparently healthy individuals and in patients with non-SARD inflammatory conditions. It is seen that SARD patients will have DFS 70 in association with disease-specific autoantibodies. But if present in isolation SARD diagnosis is excluded. These observations have recently stimulated vigorous research on their clinical and biological significance. The emerging role of DFS 70 is as a multifunctional stress response protein relevant to human acquired immunodeficiency syndrome, inflammation, cancer and other conditions. Thus, suggesting that these autoantibodies could be indicators of cellular stress and inflammation associated with environmental factors.
As mentioned earlier, the laboratory is challenged by inconclusive IIFT ANA findings (fine granular with positive chromosomes), without disease-specific autoantibodies using monospecific tests. These IIFT patterns can be possibly explained by antibodies against DFS 70.
The patterns of ANA observed on HEp2 cells by IIFT provide an insight into the specificity of autoantibodies present; markers like DFS 70, play a greater role in the exclusion of SARD. But this presents a unique interpretation challenge for clinical labs. So it becomes essential in the clinical setup to confirm DFS 70 by monospecific tests like ELISA or by multiplex line immunoassay to avoid unwanted confusions and increase diagnostic accuracy.
