33 Synovitis is dominated by shared T-cell clones notypically unchanged state, which is currently difficult to perform routinely on a large scale. Hopefully, novel technologies for single-cell characterization will rapidly develop to allow this in the near future. A striking observation is the difference in TCR repertoire when comparing SF to ST. Previous literature showed an overlap of clones between ST, SF, and PB, but the exact quantitative relation between clones in the different compartments could not be found [36]. An early pilot study already showed that the overlap of TCRβ clones between ST and PB is low (4%) [9]. The present study clearly validates this, but the apparent quantitative difference between TCRβ clones (especially when focusing on the expanded clones) of the SF and ST that we determined was not shown before. Thus, it seems that the ST and SF are two separate compartments instead of one. This is supported by the similarity index, which confirms that the SF shows significantly more overlap with the ST than the PB does. In contrast, the top 25 overlap between ST and SF is as low as the top 25 overlap between ST and PB, indicating that although the general overlap is quite high, this is not the case for the highly expanded ST TCRβ clones. Hence, for future T cell studies in RA, it would be recommended to regard ST and SF as separate compartments and use caution when extrapolating T cell findings from SF to ST. Our data show clear oligoclonal expansions in the ST and show that the same TCRβ clones dominate the repertoires in biopsy specimens from different regions in the same joint. Even with a very stringent top 25 overlap analysis, we show a large number of overlapping TCRβ clones. These findings imply that single-locus ST biopsies can be used instead of multilocus biopsies when studying T cells. One can therefore speculate that ultrasound (US)-guided or even blind needle biopsies might be just as informative on the T cell repertoire as biopsies taken via arthroscopy. This would improve accessibility because US-guided or blind needle biopsies can be performed at the outpatient clinic, whereas arthroscopy requires theater time. Moreover, these procedures are minimally invasive, well tolerated, and take less time to perform. An earlier study already showed that the quality and RNA yield is preserved in US-guided procedures [37]. Ideally, a follow-up study comparing specimens from US-guided or blind needle biopsies to biopsy specimens obtained via arthroscopy (from the same joint) should be performed to test this. It should be noted that we sequenced the TCR β-chain only; thus, it remains possible that the identified sequences correspond to “public” sequences (i.e., clones that have the same TCR β-chain but have a different TCR α-chain). This might or might not drive a similar Ag specificity of the receptor depending on the TCR α-chain it is 2
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