In the present study, we notably found that sera from SLE patients profoundly elicit immunoreaction against AHNAK1 when compared to normal healthy controls (NHCs) or patients with other systemic autoimmune diseases, such as polymyositis/dermatomyositis (PM/DM), systemic sclerosis (SSc), Sjögren’s syndrome (SjS), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA). This evidence concerns the gene AHNAK and mixed connective tissue disease.