Abstract
Clinical and diagnostic laboratories often encounter patient sera containing antinuclear antibodies (ANAs) that produce a nuclear dense fine speckled immunofluorescence pattern on HEp-2 cells. These autoantibodies usually target the dense fine speckled protein of 70 kDa (DFS70), commonly known as lens epithelium-derived growth factor p75 (LEDGFp75). Anti-DFS70/LEDGFp75 autoantibodies have recently attracted much interest because of their relatively common occurrence in sera from patients with positive ANA tests with no clinical evidence of systemic autoimmune rheumatic disease (SARD). Their presence has been documented primarily in patients with diverse non-SARD inflammatory conditions and “apparently healthy” individuals. While there is circumstantial evidence that depending on the context these autoantibodies could play protective, pathogenic, or sensor roles, their significance remains elusive. DFS70/LEDGFp75 has emerged during the past decade as a stress transcription co-activator relevant to HIV integration, cancer, and inflammation. It is not clear, however, what makes this protein the target of such a common autoantibody response. We suggest that a better understanding of DFS70/LEDGFp75 biology is key to elucidating the significance of its associated autoantibodies. Here, we discuss briefly our current understanding of this enigmatic autoantigen and potential scenarios leading to its targeting by the immune system.
Highlights
The clinical and biological significance of anti-dense fine speckled protein of 70 kDa (DFS70)/LEDGFp75 autoantibodies has been puzzling because in spite of being relatively common and capable of reaching high titers, they lack disease specificity and can be found in “apparently healthy” individuals and in patients with diverse non-systemic autoimmune rheumatic disease (SARD) inflammatory conditions (1–7)
We suggest that a better understanding of DFS70/LEDGFp75 biology is key to elucidating the significance of its associated autoantibodies
That in our quest to elucidate the biological and clinical significance of humoral autoimmunity to anti-DFS70/LEDGFp75, we should take into account the following key observations: (1) The nuclear dense fine speckles (DFS)-indirect immunofluorescence (IIF) pattern produced by anti-DFS70/LEDG Fp75 autoantibodies is the most common antinuclear antibodies (ANAs) pattern in sera from patients with non-SARD diagnosis referred to clinical diagnostic laboratories (4, 5)
Summary
The clinical and biological significance of anti-DFS70/LEDGFp75 autoantibodies has been puzzling because in spite of being relatively common and capable of reaching high titers, they lack disease specificity and can be found in “apparently healthy” individuals and in patients with diverse non-SARD inflammatory conditions (1–7). DFS70/LEDGFp75 contributes to the activation of these genes by forming complexes with multiple chromatin-associated proteins Both the N- and C-terminal portions of DFS70/LEDGFp75 participate in its transcription and stress survival functions. The PS1P1/LEDGF gene has been mapped to chromosome 9p22.2 region, which is adjacent to a locus associated with the 9p deletion syndrome, a rare human chromosomal abnormality characterized by atypical craniofacial features, inability to nurse and breath, eye diseases, and several other anomalies It remains to be determined if loss of DFS70/LEDGFp75 is a common genetic abnormality in this syndrome. HIV-IN binds to a highly conserved, C-terminal domain of DFS70/LEDGFp75 mapped to residues [347–429] and named integrase binding domain (IBD) (11) This interaction stabilizes HIVIN and contributes to DFS70/LEDGFp75-mediated shuttling of HIV-1 into the nucleus and tethering it to chromatin to promote viral integration to transcriptionally active sites. Why would an epitope region targeted by autoantibodies be the same region recognized by the HIV-IN? What elements within this region make it attractive for targeting by both the immune system and HIV-1? Would the presence of
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
