Since ANA and related autoantibodies are generally considered useful biomarkers for AARD (which have low prevalences) and are included in the classification criteria for SLE [13], MCTD [14], SjS [15] and SSc [16], ANA testing on HEp-2 substrates outside a proper clinical framework may yield a sizable portion of ANA-positive individuals without consistent evidence of AARD. This evidence concerns the gene BTG3 and systemic sclerosis.