Anne Musters

48 CHAPTER 3 19.5% of the total repertoire, in the right knee 1,701 ± 439.7 BCR-clones, with 31.7 ± 10.3 HECs accounting for 46.7% ± 13.9 of the total repertoire. To test for repertoire similarity between different joints we compared the overlap between the 25 most expanded BCR- clones in both knee joints. The overlap of the top-25 between two different joints was 9.1% ± 8.2, significantly larger than the top-25 overlap between ST and PB (1.7% ± 2.4; p = 0.02; Figures 2D, E). Comparing the total repertoires, the mean Chao-modified Sørensen index was 0.24 ± 0.15 for the ST-ST comparison, significantly higher than the index between ST and PB (0.05 ± 0.06; p < 0.01; Figure 2F). Both the top-25 overlap and Chao-modified Sørensen index between contralateral joints did not differ from the overlap observed when comparing two ST- regions within one joint (p = 0.08 and p = 0.36 respectively). Together, these data demonstrate that the BCR repertoire in ST from the knee shows substantially more overlap with the repertoire in ST of the contralateral knee than with PB. Figure 2 | Comparing B-cell receptor repertoires in two contralateral inflamed joints Bar charts of (A) the number of BCR-clones, (B) number of highly expanded BCR-clones (HECs) and (C) impact of HECs on total repertoire per joint (bars show mean and SD; ns=not significant using a one- tailed Mann-Whitney test). (D) Representative example of overlap-plots from one patient when comparing the ST of the left (L) joint to right (R) joint, showing substantial overlap; for explanation see legend Figure 1D (E) Scatterplot of the impact of the top-25 overlapping BCR-clones and (F) the Chao-modified Sørensen indices of the total BCR-clonal repertoire when comparing different compartments (n=7; lines at mean and SD; * p<0.05, ** p<0.01 using a paired t test).

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