Besides, our data suggest that NETosis is a non-canonical release mechanism for ISG15, suggest H2B as a probable substrate for ISG15 in SLE patients and these ISG15-containing NETs from SLE patients promote enhanced production of IFNγ, implying a new field in pleiotropic functions of PTM promoting tolerogenic and immunogenic responses during autoimmune diseases. The gene discussed is IFNG; the disease is autoimmune disease.