Supporting this hypothesis, it has been shown that (i) citrullinated fibrinogen could induce arthritis in DRB1*04:01 transgenic mice [15], (ii) proinflammatory cytokines were produced by CD4+ T cells in SE+ individuals in response to citrullinated self-epitopes [16], (ii) citrulline-specific Th1 and Th17 cells are increased in HLA-DRB1*04:01+ RA patients [17, 18], and (iii) RA patients display Th17 cells responding to arthritogenic citrullinated aggrecan [19]. Here, ACAN is linked to rheumatoid arthritis.