A new article published in Lupus discussed that autoantibodies (AA) and antinuclear antibodies (ANA) serve as key diagnostic and classification criteria for systemic lupus erythematosus (SLE). More than 200 different AA have been reported in SLE, although only a handful (<20) are widely and routinely used in diagnostic, research and clinical medicine. Although the vast majority of AA have been relegated to the diminished status of orphan AA, some serve as predictors of SLE because they first appear in very early or subclinical SLE. The authors reported that some AA are pathogenic, whereas others are thought to protect against or ameliorate disease progression. Moreover, they can be used as predictive biomarkers of prognosis. Although studies have shown that specific AA are detected in the preclinical phase of SLE and are biomarkers of increased risk of developing the disease, AA are currently not widely used to predict very early SLE in individuals who have low pretest probability of disease. In inference, it was stated that emerging evidence indicates that when certain combinations of biomarkers, such as the interferon signature and stem cell factor accompany AA and ANA, are use, the predictive power for SLE is markedly increased.