Based on the finding that the anti-perinuclear factor, an autoantibody highly specific for RA, is directed to citrullinated filaggrin, the first-generation anti-CCP (anti-CCP1) utilized filaggrin-derived cyclic rather than linear citrullinated peptides to improve antibody recognition but was not widely used due to low sensitivity [35]. Here, FLG is linked to rheumatoid arthritis.