PKCβ1 was identified as the relevant kinase and PP1 as the relevant phosphatase for phosphorylation and dephosphorylation of Ser81 of PGRN in patients with autoimmune diseases, and hyperphosphorylated PGRN was found to lack its binding activity to TNFR1, TNFR2 and DR3, and thereafter lost anti-TNF functions. This evidence concerns the gene TNFRSF1A and autoimmune disease.