Fig. 4: Descartes-08 selectively regulates inflammatory response without immune suppression.
a–e, Change in CD19+ B cells (a), CD20+ B cells (b), T cells (c), natural killer (NK) cells (d) and monocytes (e) as measured by flow cytometry at month 3 in placebo patients (n = 10), at month 3 in DC-08 patients (n = 11) and at month 12 in DC-08 patients (n = 7) compared to SCR. f–h, Change in immunoglobulin G (f), immunoglobulin A (g) and immunoglobulin M (h) titers at month 3 in placebo patients (n = 15), at month 3 in DC-08 patients (n = 19) and at month 12 in DC-08 patients (n = 13) compared to SCR. i–m, Change in anti-measles (i), anti-mumps (j), anti-rubella (k), anti-diphtheria (l) and anti-tetanus (m) vaccine titers at month 3 in placebo patients (n = 15), at month 3 in DC-08 patients (n = 19) and at month 12 in DC-08 patients (n = 13) compared to SCR. n–ab, Change in abundance of serum factors analyzed by Olink Target 96 Inflammation panel and expressed as difference in log2-scaled NPX between indicated timepoint and respective SCR sample. n, Change in abundance of significantly changed inflammatory factors, along with additional analytes of interest at day 1 (n = 19). Significant changes in LTA (P < 0.001), β-NGF (P = 0.006), TGF-β1 (P < 0.001), CD6 (P = 0.010) and IL-7 (P = 0.018) occurred after leukapheresis (n = 19). o–t, Change in abundance of inflammatory factors, including IL-6 (o), IL-24 (p), CCL19 (q), ARTN (r), RANKL (s) and VEGFA (t), after treatment with DC-08 compared to month 3 in placebo patients (n = 10) and DC-08 patients at month 1 (n = 11), month 3 (n = 11) and month 12 (n = 7). Decreases in IL-6 (P = 0.019) and IL-24 (P = 0.008) occurred at month 3 in DC-08-treated patients relative to placebo (o,p). u–x, Change in abundance of inflammatory cytokines, including IL-6 (u), CCL19 (v), RANKL (w) and VEGFA (x), in the DC-08 patient cohort between clinical responders at month 1 and month 3 (n = 6) and non-responders at month 1 and month 3 (n = 5). RANKL was significantly reduced in responders at month 1 (P = 0.035) and month 3 (P = 0.030) (w). y–ab, Change in abundance of inflammatory cytokines, including IL-6 (y), CCL19 (z), RANKL (aa) and VEGFA (ab), in the DC-08 patient cohort between patients who had not received prior treatment with biologics (that is, complement inhibitors, FcRn inhibitors or CD19/CD20-targeting antibodies) at month 1 and month 3 (n = 5) and patients who had received prior biologics at month 1 and month 3 (n = 6). IL-6 (P = 0.010), CCL19 (P = 0.002) and VEGFA (P < 0.001) were significantly decreased at month 1 in patients who had not received biologics prior to DC-08 (y–ab). Additionally, VEGFA was significantly decreased in patients who had not received biologics prior to DC-08 at month 3 (P = 0.003). For lymphocyte subsets, immunoglobulin titers and vaccine titers, P values were generated with a two-sided unpaired t-test for each comparison between treatment groups and a paired two-sided t-test between longitudinal timepoints within each treatment group. For cytokine analysis, P values were generated using a linear mixed-effects model. 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. NS, not significant.
