Fig 1: Heatmap representing Z-scores of different rheumatoid factor (RF) isotypes in rheumatoid arthritis (RA) patients and controls. RF from 27 RF(+)/anti-cyclic citrullinated peptide (anti-CCP)(+) RA patients, five RF(−)/anti-CCP(+) RA patients, 22 RF(−)/anti-CCP(−) RA patients, 28 RF(−) disease controls, and four RF(+) disease controls was isolated, digested into peptides, and analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Z-score of Ig heavy chain protein isotypes was compared in different disease groups. p-Value annotation for comparison of seropositive patient samples [RF(+)/anti-CCP(+)RA] versus disease control samples [RF(−)/anti-CCP(−) C] using Kruskal–Wallis testing followed by post-hoc Dunn’s test: *p < 0.05 and **p < 0.001. p-Value annotation for comparison of seronegative patient samples [RF(−)/anti-CCP(−) RA] versus disease control samples [RF(−)/anti-CCP(−) C] using Kruskal–Wallis testing followed by post-hoc Dunn’s test: ^p < 0.05 and ^^p < 0.001. Regarding IgM and IgG1, two UniProt accessions were found in PEAKS software (P0DOX5 and P01857 for IgM and P0DOX6 and P01871 for IgG1). As they have a high correlation and similar sequences, as shown in Supplementary Figure 13 , only one accession number is illustrated in this figure. UniProt accession numbers corresponding with the protein description as listed in this figure are P01876, P0DOX2, P01857, P01859, P01860, P01861, and P01871.
Fig 2: Quantification of Ig heavy chain rheumatoid factor (RF) isotypes in rheumatoid arthritis (RA) patients and controls. RF from 27 RF(+)/anti-cyclic citrullinated peptide (anti-CCP)(+) RA patients, five RF(−)/anti-CCP(+) RA patients, 22 RF(−)/anti-CCP(−) RA patients, 28 RF(−) disease controls, and four RF(+)/anti-CCP(−) disease controls was isolated, digested into peptides, and analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Protein abundance of Ig heavy chain isotype was obtained by totaling the peptide abundances of unique peptides per protein. Area under the curve for each protein is listed. Regarding IgM and IgG1, two UniProt accessions were found in PEAKS software (P0DOX5 and P01857 for IgM and P0DOX6 and P01871 for IgG1). As they have a high sequence similarity (shown in Supplementary Figure 13 ), only one accession number is illustrated in this figure. UniProt accession number P01871 represents the heavy mu chain, and accession P01857 represents IgG1 subclass.
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