Research projects

Among autoimmune diseases, systemic lupus erythematosus represents the genetic prototype. It is well known that, of all these diseases, this is the one in which genetic factors play the most important role. Genetic studies have demonstrated a high degree of allelic heterogeneity, and it is very likely that what seems to be a disease is actually a syndrome covering a range of diseases cause by different genetic defects. This project uses massive sequencing methodology to identify rare mutations in individuals belonging to families of European origin with lupus, in which at least two patients are related in the first, second or third degree. Once the mutations have been identified, the effects they may have on the expression and function of the affected protein will be clarified. A mutation in the BLK susceptibility gene was identified in a preliminary study. The change of amino acid leads to greater degradation of the BLK protein. Moreover, the mutation is located in the SH3 domain of the protein, which is important for its binding to other interacting proteins. The results of this project will have important consequences for the understanding of the aetiology and pathogenesis of this disease and may help to elucidate the differences between patients, bringing us ever closer to possibilities of personalised medicine.