ACAN and rheumatoid arthritis: Most recently, two independent laboratories have reported that a citrullinated version of the 5/4E8 epitope-containing aggrecan peptide VVLLVATEGR/CitVRVNSAYQDK (5/4E8 sequence bold-faced in italics and arginine/citrulline [R/Cit] substitution underlined) induced substantial cytokine (IL-17, IL-22, IL-6, TNFα, and IFNγ) production by T cells from the majority of RA patients [58, 110].