Abstract
BackgroundAutoimmune 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.MethodsIn 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.ResultsThe 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.ConclusionThis 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.
Highlights
Autoimmune diseases are syndromes characterized by an immune response against self-antigens
The expression of Ikaros interexonic regions in Autoimmune diseases (AIDs) When we analysed the expression of the Ikaros interexonic regions, significant differences were observed in regions IE2–3 (x2 = 16.5; p < 0.01), IE3–4 (x2 = 17.1; p < 0.01), IE4–5 (x2 = 32.8; p < 0.0001) and IE6–7 (x2 = 30.8; p < 0.0001)
For IE3–4, individuals diagnosed with systemic lupus erythaematosus (SLE) had lower levels and individuals with rheumatoid arthritis (RA) had the highest expression levels of this region with respect to the controls and SLE and s syndrome (SS) patients, and the differences were significant in both cases
Summary
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. The high level of alternative splicing can generate multiple isoforms from each gene, including isoforms that arise from non-canonical splicing due to insertions and deletions [12,13,14] Some of these, such as Ik6, act as dominant negative (DN) isoforms and have been associated with certain haematological pathologies [15,16,17]. These isoforms can kidnap functional isoforms (Ik1, Ik2, Ik3, etc.) in the cytoplasm, inhibiting their action on its target genes and restricting their role as transcription factors [18]
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