Autoimmune diseases are syndromes characterized by an immune response against self-antigens. They are complex pathologies associated with a variety of genetic determinants, but these genes cannot fully explain the aetiology of autoimmune disorders. Ikaros is a transcription factor that plays a major role in lymphoid differentiation. In this study, we characterized the expression profiles of Ikaros isoforms by quantifying the interexonic regions of patients diagnosed with Sjögren’s syndrome, systemic lupus erythaematosus, systemic sclerosis and rheumatoid arthritis in RNA extracted from peripheral blood. REST software was used for relative quantification and Hierarchical clustering analysis was performed using Cluster and TreeView. The expression of Ikaros was altered in all diseases examined. Significant differences were found in all of the interexonic regions between the comparison groups. Decreased expression of the IE3–4, 4–5 and 5–6 regions in all of the autoimmune pathologies was associated with the presence of dominant negative isoforms. Differences in the expression of several exons in rheumatoid arthritis and systemic lupus erythaematosus indicated the presence of different isoforms, which could serve as biomarkers for these diseases. This study is the first conducted in Latinamerica that sought to determine the relationship between Ikaros and autoimmune diseases and is the first description of Ikaros in patients with rheumatoid arthritis, Sjögren’s syndrome and systemic sclerosis. Furthermore, we confirmed that Ikaros expression is altered in systemic lupus erythaematosus.