Fig. 3: Descartes-08 exerts precision effects against plasmablasts, pDCs and autoantibodies.
a,b, Pretreatment (SCR) frequencies of plasmablasts (a; n = 9) and pDCs (b; n = 12) by flow cytometry with corresponding reference ranges for healthy individuals. Mean ± s.e.m. with all data points shown. c,d, Pretreatment MG versus HD BCMA protein expression on plasmablasts (c; MG, n = 9; HD, n = 10) and CD86 protein expression on pDCs (d; MG, n = 12; HD, n = 10), measured by flow cytometry. Data show MFI with mean ± s.e.m. with all data points shown. e,f, Flow cytometric analysis of absolute change in BCMA expression in plasmablasts at month 1 (n = 9 participants per group) and month 3 (placebo, n = 7; DC-08, n = 6) (e) or CD86 expression in pDCs at month 1 (n = 11 participants per group) and month 3 (n = 10 participants per group) (f) measured by MFI for placebo and DC-08 groups at month 1 and month 3 relative to respective SCR samples. g,h, Flow cytometric analysis of plasmablast (g) and pDC (h) frequency for placebo and DC-08 groups at month 1 and month 3 relative to respective SCR sample (sample sizes as per e and f). i, Heatmaps showing the Pearson correlation coefficient statistics (r) of comparisons between PhIP-Seq autoreactomes for longitudinal samples collected from placebo participants (n = 14) and DC-08 participants (n = 16). The series (left to right and top to bottom) is ordered by participant and then by timepoint (day 1, month 1 and month 3). Central diagonal indicates the correlation of each autoreactome against itself (providing r = 1 by definition). j, Assessment of autoantibody repertoire turnover via correlation of PhIP-Seq autoreactome for patients treated with placebo at month 3 (r value median = 0.89) (n = 14), DC-08 at month 3 (r value median = 0.72) (n = 16) and DC-08 at month 6 (r value median = 0.74) (n = 10) relative to respective day 1 autoreactome, showing a significant decrease in r value at month 3 in DC-08 participants relative to placebo (P = 0.034). k, Evaluation of the effect of leukapheresis on the autoantibody repertoire. Data show Pearson correlation coefficient (r) for all day 1 autoreactomes compared against participant-matched SCR autoreactome (r value median = 0.68) (n = 19). l, Evaluation of fold change in anti-AChR autoantibody titer against absolute change in clinical MG status (measured by MG-ADL scale) for comparison of month 3 against month 1 across placebo-treated and DC-08-treated participants with measurable anti-AChR titer at SCR (n = 21). m, Fold change in the level of anti-AChR binding antibody titer after treatment with placebo at month 3 (n = 11), DC-08 at month 3 (n = 13) and DC-08 at month 6 (n = 9) relative to respective day 1 titer for all participants with measurable anti-AChR titer at SCR. P values were generated with a two-sided unpaired t-test for each comparison between treatment groups and paired two-sided t-test between longitudinal timepoints within each treatment group. Box-and-whisker plots show the median, interquartile range and full range of data, along with individual data points. Source data are provided for this figure. D, day; M, month.
