30 CHAPTER 2 (Fig. 2A, 2B). The impact of the HECs on the total repertoire was 18.9% (mean, SD 14.5) and 18.5% (SD 10.6), respectively, which was also not significantly different (Fig. 2C). Next, we compared the overlap between the 25 most expanded TCRβ clones in both joints. In line with the findings on different locations within the same joint, we again observed that 50.2% (mean, SD 14.9) of the 25 most dominant ST TCRβ clones were identical between different joints (p = 0.30, Fig. 2E). Last, the Chao-modified Sørensen index as a measurement for similarity was assessed. In contrast to what was hypothesized, the Chao-modified Sørensen index also demonstrated large overlap, with a mean score of 0.43 (SD 0.11) (Fig. 2F). Both ST–ST overlap analyses showed significantly higher overlap when compared with overlap between ST and PB (p < 0.001, p < 0.0001, respectively, Fig. 2E, 2F). The Chao-modified Sørensen index between contralateral joints did not differ from the ST overlap observed when comparing two regions within one joint (i.e., IP versus SP [p = 0.12]). In summary, these data support the notion that TCR repertoires in ST biopsy specimens taken simultaneously from two different (contralateral) inflamed joints show substantial overlap. Figure 2 | Comparing T-cell receptor repertoires in two contralateral inflamed joints Bar charts of (A) the number of TCRβ-clones, (B) number of highly expanded TCRβ-clones (HECs) and (C) impact of HECs on total repertoire per joint (bars show mean and SD; using a one-tailed Mann-Whitney test). (D) Example of overlap-plots from one patient when comparing the ST of the left (L) joint to right (R) joint, showing substantial overlap. Scatter plot of (E) percentage of overlapping top-25 TCRβ-clones and (F) Chao-modified Sørensen indices of the total TCRβ-clones repertoire when comparing different compartments (n=9; lines at mean and SD; *** p < 0.001, **** p < 0.0001 using a paired t test).
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