29 Synovitis is dominated by shared T-cell clones Collectively, these findings demonstrate that in the inflamed RA ST, the TCR repertoire shows substantial similarity at different regions within one joint and is dominated by the same TCRβ clones. Such overlap is not observed when comparing ST to PB. Figure 1 | Comparing T-cell receptor repertoires within one joint 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 compartment (bars show mean and SD; using a Tukey’s multiple comparison test). (D) Example of overlap-plot from one patient comparing the suprapatellar (SP) to the infrapatellar (IP) synovial tissue (ST) region, showing clear overlap of dominant TCRβ-clones in the upper right quadrant; (E) Comparison of ST to peripheral blood (PB), showing little overlap. Scatter plots of (F) percentage of overlapping top-25 TCRβ-clones and (G) Chao-modified Sørensen indices of the total TCRβ-clones repertoire when comparing different compartments (n=14; lines at mean and SD; **** p<0.0001 using a paired t test). Do different T cell clones dominate the TCRβ repertoire in multiple joints? Polyarthritis is a hallmark feature of RA. To the best of our knowledge, no quantitative analysis exists on whether different T cell clones dominate the TCR repertoire in multiple joints. To test this hypothesis, we compared the TCRβ repertoires from ST biopsy specimens simultaneously taken from two inflamed contralateral joints (left and right; either knee or ankle) from nine RA patients (see Table 1 for characteristics). We analyzed paired PB samples as a control. The general features of the ST TCR repertoires from contralateral joints were not significantly different: in the left joint, we identified 7124 TCRβ clones (mean, SD 2665) with 7.1 HECs (mean, SD 2.8); in the right joint, we observed 6735 TCRβ clones (SD 3452) and 9.7 HECs (SD 5.2) 2
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