Anti-DFS70 antibodies in systemic lupus erythematosus and lupus nephritis: revisiting their clinical implications

Antibodies against the Dense Fine Speckled 70 kDa protein (anti-DFS70), associated with the anti-cell 2 (AC-2) pattern on immunofluorescence HEp-2 cells, represent a frequent finding in antinuclear antibody (ANA) testing, particularly among healthy individuals, and have been proposed as an exclusion marker for systemic autoimmune rheumatic diseases (SARDs). In systemic lupus erythematosus (SLE), however, their interpretation is more complex. Anti-DFS70 antibodies are uncommon, rarely monospecific, and are not consistently associated with global disease activity, although selective associations with musculoskeletal and mucocutaneous manifestations have been reported. In lupus nephritis (LN), evidence from a single dedicated cohort suggests that anti-DFS70 antibodies are enriched compared with healthy controls and patients with non-lupus chronic kidney disease (CKD), while within biopsy-proven LN they may associate with proliferative histological subtypes and intrarenal inflammatory activity. In this narrative review, we provide a critical overview of the epidemiological, serological, clinical, and experimental evidence on anti-DFS70 antibodies, with a particular focus on SLE and LN. Overall, current evidence supports a context-dependent interpretation of anti-DFS70 antibodies across health, systemic autoimmunity, and organ-specific inflammation.