IF-ANA detected by HEp-2 cells appear a reliable and stable marker of the disease in a real-world cohort of SLE patients with and without renal involvement and during a long follow-up. In fact, IFANAbecame negative in only 8% of patients and around 40% of them showed a decrease in IF-ANA titer during the follow-up, independent of disease characteristics and treatment. The evaluation of clinical and laboratory data from different clinical centers further stresses the reproducibility of the finding. Additional studies to clarify the mechanisms responsible for IF-ANA seroconversion and titer variation in SLE patients are warranted.