Novel RSAD2 isoforms lacking antiviral activities are originated from alternative splicing and expressed in patients with rheumatic diseases.

Systemic lupus erythematosus (SLE) and Rheumatoid arthritis (RA) are systemic and autoimmune rheumatic diseases resulting from the loss of immune self-tolerance through overproduction and secretion of cytokines by leukocytes. Here we show that the expression of RSAD2, a type 1 interferon-inducible gene involved in broad antiviral cell responses, is increased in SLE and RA patients in the form of two novel shorter isoforms. Sequencing of the whole cDNA for these novel RSAD2 isoforms show they are originated from the simultaneous use of 5' and 3' alternative splicing sites in the pre-mRNAs of two previously reported RSAD2 isoforms. This form of alternative splicing produces isoforms that lack important functional domains that renders them unable to both fight viral infections and interfere with the secretion of soluble proteins, like cytokines. Our work suggests a link between alternative splicing in humans and rheumatic diseases.