31 Synovitis is dominated by shared T-cell clones Are TCR repertoires in ST and SF dominated by different T cell clones? Besides synovitis, joint effusion is also a feature of arthritis. As SF can be acquired with a less invasive procedure than ST, fluid is often used to study certain aspects of the pathogenesis of arthritis. However, it is not known whether the T cell repertoires from ST are similar to those from SF in the same joint. To address this, we included seven RA patients (see Table for characteristics) from whom we obtained paired samples: ST biopsy specimens and SF from the same joint as well as PB as control. In ST, we detected 6781 TCRβ clones (mean, SD 2759) compared with 4923 TCRβ clones in SF (SD 3048, Fig. 3A). We identified 8.2 HECs in ST (mean, SD 4.0) and 18.7 HECs in SF (SD 15.6, p < 0.001, Fig. 3B). The HECs accounted, respectively, for 23.0% (mean, SD 18.5) and 45.3% (SD 27.2) of the total repertoire (p < 0.05, Fig. 3C). ST and SF differed significantly from PB regarding the number of TCRβ clones (features described earlier in this article; p < 0.05, p < 0.01, respectively), whereas the number of HECs in ST and SF was significantly different from that in PB (both p < 0.01, Fig. 3A–C). Comparing ST to SF from the same joint, the top 25 overlap was 26.0% (mean, SD 14.8). The top 25 overlap between SF and PB was 18.0% (SD 8.8, Fig. 3F). Thus, the top 25 analysis did not differ significantly between the ST–SF, SF–PB, and ST–PB comparisons. Comparing all TCRβ clones using the Chao-modified Sørensen index for ST to SF resulted in an index of 0.41 (mean, SD 0.13), whereas we noted an index of 0.13 for the SF–PB comparison (SD 0.06, Fig. 3G). The Chao-modified Sørensen index of the ST–SF comparison did significantly differ from the SF– PB and ST–PB comparisons (p < 0.001, p < 0.0001, respectively). Moreover, within one joint, both results from the top 25 overlap and Chao-modified Sørensen index differed significantly when comparing the intrajoint ST–SF overlap to the intrajoint ST–ST (IP versus SP regions) overlap as described earlier (Fig. 3F, 3G). In summary, these data show that the dominant TCRβ clones from ST are not fully reflected in SF and even less so in PB. Moreover, significantly less similarity between ST and SF/PB was observed compared with the high similarity seen within ST biopsy specimens taken from different locations in the same joint. 2
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