Precise regulation of the immune system is crucial for homeostasis maintenance. Autoimmunities are complex disorders that have in common alterations in immune homeostasis, and in order to be fully understood approaches that take into consideration their complexity are needed. In systemic sclerosis patients, levels of type I Interferons and 2’5’-oligoadenylate synthetase genes are found upregulated. In 2013, an approach that quantified each individual 2’5’-OAS gene in patients revealed that there is a differential upregulation of this gene family. The hypothesis is that during the disease patient cells are refractory to circulating type I Interferons and that an unknown stimuli is differentially inducing OAS2 and OASL genes. It can be taken as an example that the complexity of the immune system and its components must be taken into consideration to satisfactory understand autoimmunities.