126 CHAPTER 6 Other BCRh repertoire features such as the diversity of the BCRh repertoires, the percentage of unmutated BCRh clones at the timepoint of B cell repopulation after rituximab as well as the persistence of the top 25 most expanded clones at screening did not differ between RA developers and non-developers (Figure 2D-2F). In conclusion, in the RTX-group the BCRh repertoire is comparable between RA developers and non-developers during the follow-up period. Figure 2 | Influence of rituximab on the BCRh repertoire in RA-risk individuals Dot plots of (A) the number of BCRh clones during the at-risk phase for individuals that did or did not develop RA, (B) the absolute number of dominant BCRh clones during the at-risk phase for individuals that did or did not develop RA and (C) impact of the dominant BCRh clones on the total BCRh repertoire during the at-risk phase for individuals that did or did not develop RA (D) Simpsons index of the BCRh repertoire during the during the at-risk phase for individuals that did or did not develop RA (E) Percentage of unmutated BCRh clones in the repertoire at various timepoints during the at-risk phase for individuals that did or did not develop RA. (F) Dots plots of top 25 clonal overlaps between the screening visit and 6 months after treatment during the at-risk phase for individuals that did or did not develop RA. The dynamics of the BCRh repertoire in untreated and placebo-treated at-risk individuals Since the BCR repertoire of the PRAIRI-placebo-group did not differ from the untreated DOMINO group at screening (Supplementary figures 1D-1F), different time points during follow-up in both groups were compared, to investigate whether the BCRh repertoire changed over time. An additional comparison could be made to estimate the effect of vaccination and methylprednisolone, which were given to the PRAIRI-placebo-group on screening and baseline respectively. Differences in number and impact of dominant clones, throughout follow-up visits, including an eventual arthritis time point did not reach significance (Figure 3A-D and supplementary figure 2A-B). This suggests that the results in the PRAIRI-placebo-treated
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