(A) The heat map shows an overview ... (A) The heat map shows an overview of serum antibodies’ responses towards all cyclic CII peptide in RA and OA patients. The colour key indicates the strength of the antibody response. (B) Principal component analysis (PCA). Each red dot represents an RA patient, while each black triangle represents an OA patient. The circle represents a 95% confidence interval of the analysis. (C) The contribution of each peptide derived from PCA analysis, with each black dot representing a peptide and the colour key indicates the contribution of peptides. R: arginine; CIT: citrullinine; Dim1: Dimension 1; Dim2: Dimension 2. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Rheumatology (Oxford), kez073, https://doi.org/10.1093/rheumatology/kez073 The content of this slide may be subject to copyright: please see the slide notes for details.

The ... The black dot represents one patient sample, the red dotted line represents the cut off value (median + 5MAD) of the peptide reactivity. Comparison between RA and OA patients with cyclic citrullinated peptides of the C1, U1, E10 and the F4 epitope on CII (A), and also two newly identified epitopes on CII, 2-CIT and 46-CIT, the RA samples have a significantly higher response to the peptides (B). A similar result also exists when comparing the RA and HC (C and D). P values calculated by Mann–Whitney U test are given under each image. CIT: citrullinine; HC: healthy controls; MAD: median absolute deviation. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Rheumatology (Oxford), kez073, https://doi.org/10.1093/rheumatology/kez073 The content of this slide may be subject to copyright: please see the slide notes for details.

(A) The number of peptides that were responded by each ... (A) The number of peptides that were responded by each patient was shown. In summary, 31 out of 95 CCP2 negative RA patients respond to at least one peptide in the top 10 category, but 20 out of 322 CCP2 positive RA patients give no response. (B) The correlation plot among the top 10 peptides and the Spearman coefficient was also shown in the plot. (C) The scatter plot of pair-wise comparison for the two peptides that react to RA patients. The dashed line represents the cut off value (median +5×MAD) of peptide reactivity. The lower-left and upper-right quadrants indicate double negative or positive responses, others indicate the single positive reaction. JP2: joint peptide 2 (collagen type II peptide); CIT: citrullinine. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Rheumatology (Oxford), kez073, https://doi.org/10.1093/rheumatology/kez073 The content of this slide may be subject to copyright: please see the slide notes for details.

The 54 peptides were classified into nine groups based on the ... The 54 peptides were classified into nine groups based on the binding profiles among all the RA patients. The calculations and dendrogram were based on the hierarchical cluster analysis performed in Fig. 1A. The sequences of all peptides are shown in Supplementary Table S1, available at Rheumatology online. The conservation was analysed and shown by SeqLogo, where the frequency of residues in each position was plotted. The chemical properties of each residue were also marked. The reactivity profile for each group is represented as a gradient circle, where dark represents the highest response, and light grey represents negligible response. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Rheumatology (Oxford), kez073, https://doi.org/10.1093/rheumatology/kez073 The content of this slide may be subject to copyright: please see the slide notes for details.