Since ANAs and related autoantibodies are generally considered useful biomarkers for SARD and are included in the classification criteria for SLE [16] and systemic sclerosis (SSc) [17], ANA testing on HEp-2 substrates outside a proper clinical framework may yield a sizable portion of ANA-positive individuals without consistent evidence of SARD, purportedly leading to inappropriate referrals to tertiary care specialists, as well as anxiety in patients and physicians alike [13] and, perhaps, inappropriate and potentially toxic therapies [18]. Here, BTG3 is linked to systemic lupus erythematosus.