Aside from questioning the importance of autoantigen specificity in autoimmune disease pathogenesis, this model makes it difficult to explain, for example, how an initial antibody response to XIST RNP will drive the production of antibodies to citrullinated antigens in RA or anti-dsDNA antibodies in SLE years before the onset of disease. This evidence concerns the gene XIST and systemic lupus erythematosus.