Histone-reactive SLE IgG autoantibodies recognize acetyl-H2B. Sera from patients with SLE or healthy subjects were profiled on Human Epigenome Microarray Platform (HEMP) and probed with a secondary anti-human IgG antibody. Samples (rows) are clustered hierarchically based on corresponding reactivity profiles to the depicted peptide epitopes from HEMP arrays (columns). The depicted histone peptides (columns) were selected to match those interrogated by immunoblot assays in Figure 4 and Additional file 1: Supplemental Figures 2 and 4, with specific PTMs epitopes shown at top according to the PTM key. Heatmap tiles reflect magnitude of IgG autoantibody binding reactivity, according to the mean fluorescence intensity (MFI) intensity scale as indicated. The left heatmap panel consists primarily of peptides containing mono-, di- and tri-methyl lysine PTMs, while the right panel consists of peptides containing a variety of PTMs, including citrulline, acetyl, phosphoryl, and both symmetric (s) and asymmetric (a) di-methyl arginine. Blue asterisks (*) mark significant differences in autoantibody binding reactivity between histone positive samples and a combined group of histone negative and healthy control samples, as determined by Significance Analysis of Microarrays (SAM). IgG, immunoglobulin G; K, lysine; MFI, mean fluorescence intensity; nd, not detected; PTM, post-translational modification; R, arginine; SLE, systemic lupus erythematosus.