52 CHAPTER 3 cells and B-cells, obviously dependent on the activation status of the B-cell [24,25]. As noted above, the observed BCR clonality might thus in part reflect selective maturation rather than proliferation in the individual joint. We do not think that the fact that our analysis is only based on heavy chain analysis renders our results less valid: the enormous variability in the heavy chain produced by somatic rearrangement and mutation is sufficient to distinguish the different clones for the purpose of our clonality analysis. However, for further functional assays identification of the linked light chain is clearly desirable, e.g. using single cell analysis. In conclusion, BCR repertoires in biopsies from inflamed ST from different sites within one joint, from different joints and from SF share dominant BCR clones, while these clones have very low frequencies in PB. This suggests that for some B-cell (receptor) analyses both tissue biopsies and synovial fluid may be equally informative, the latter being more patient-friendly. Our results show that shared underlying B-cell responses might underly inflammation in different joints. This supports the idea that antigen- and/or receptor-specific therapies targeting a limited set of B-cell and/or T-cell receptor clones in individual patients might be feasible in rheumatoid arthritis or even in the “immune-mediated inflammatory diseases”-group at large.
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