49 Inflamed joints share dominant B-cell clones BCR-clones that are dominant in ST are shared with SF and to a lesser extent with PB The pathogenesis of arthritis is often studied by looking into the SF rather than ST. However, until recently, it was still unclear whether the adaptive immune responses in both compartments was similar. We have learned from an earlier study on T-cells that the dominant TCRb-clones in ST are not fully reflected in SF and even less so in PB [11]. However, for B-cells this was not investigated before. Therefore, we included 6 RA patients from whom we obtained simultaneously obtained samples: ST biopsies and SF from the same joint, paired with PB as control. In ST and SF we detected a comparable number of BCR- clones (1,412 ± 598 vs. 2,188 ± 1,385) and HECs (30.4 ± 8.0 vs. 23.2 ± 12.8; Figures 3A, B). However, the impact of the HECs on the repertoire was significantly higher for ST compared to SF (p < 0.01; 53.1% ± 17.3 versus 31.7% ± 19.2; Figure 3C). ST and SF differed significantly from PB regarding the number of BCR- clones and HECs (both p <0.0001), while the impact of HECs on the total repertoire was only significantly different between ST and PB (p < 0.0001; Figures 3A–C). The top-25 overlap in BCR clones between SF and ST from the same joint was 8.0% ± 8.8, significantly higher than the 2.7% ± 4.1 top-25 overlap between SF and PB (p < 0.05; Figures 3D–F). This top-25 overlap did not show significant differences in the comparisons ST-SF vs. ST-PB, or SF-PB vs. ST- PB. However, comparing all BCR-clones the Chao-modified Sørensen index was 0.20 ± 0.13 for the SF-ST overlap, significantly higher than the index of 0.02 ± 0.02 for the SF- PB comparison and 0.05 ± 0.06 for the ST-PB comparison (both p < 0.01; Figure 3G). Of note, the intrajoint overlap scores did not significantly differ between ST-ST and ST-SF, not when using the top-25 overlap and neither when using the Chao- modified Sørensen index (Figures 3F, G). 3
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