Myelin arrays demonstrate epitope spreading of autoantibody responses to target native and citrullinated epitopes in experimental autoimmune encephalomyelitis (EAE). EAE was induced in SJL mice using proteolipid protein (PLP) (p139–151) emulsified in complete Freund's adjuvant. Mice developed clinical EAE on days 10 to 14. On days 13, 28 and 67 serum was obtained and myelin array analysis performed. Significance Analysis of Microarrays (SAM) was used to identify antibodies with statistical differences in reactivity between the timepoints and the results displayed as a heatmap. Red boxes denote citrullinated peptides and proteins. (a) Multiclass SAM followed by cluster analysis demonstrating statistical differences in antibody reactivity differences between healthy (normal) mice and mice with acute EAE (day 13), mid-stage EAE (day 28) and long-standing EAE (Day 67). Two-class SAM followed by cluster analysis presenting differences in antibody reactivity between healthy (normal) and mice with (b) acute, (c) mid-stage and (d) long-standing EAE.