Fig. 7: Impact of SLE treatment on vaccine-mediated responses and enrichment of poor responders in patients receiving belimumab.
a, Unsupervised PCA analysis showing separation of the HD and SLE cohorts based on immunophenotypic variables. b, Luminex-based detection of RBD IgG-binding serum antibodies (net MFI values) in the HD cohort and subgroups of patients with SLE based on their treatment. The number of samples analyzed (n) is shown at the bottom of the plots. c, Proportion of patients with SLE based on their treatment among the three groups (VNL, VM and VH) of vaccine responders. d, Table with pie charts showing the percentage of VNL, VM and VH in the HD and SLE groups, as well as the relative proportion of each SLE subgroup/treatment responsiveness of the total SLE cohort. e, Neutralizing titers based on the SLE treatment group for the WA.1 strain and distribution of responders shown as a frequency of the total samples for each column. f, Cellular analysis of spike reactivity for spike++ B cells, calculated as the frequency of viable cells. g, Relative frequency of spike-reactive DN B cell populations for the HD cohort and SLE subgroups. Vertical lines indicate the s.e.m. h, Pie charts showing comparisons of the average sum for DN1 (green) versus non-DN1 (DN2 + DN3 + DN4) (white) spike++ B DN cells; the relative frequencies are shown for all vaccinated samples combined from the HD cohort and SLE subgroups. A chi-square with Fisher’s test was used for significance testing. i, AIM+ cTFH cells shown for each vaccine group and SLE subgroup. Each dot represents an individual sample. Statistical comparisons in b, e, f, h and i were performed with an unpaired, two-sided Mann–Whitney U test. When indicated, the LOD was set to logarithmic 0.001 for B cells and 0.003 for T cells. The LOS was based on median values of baseline + 2 × s.d. Not significant, P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. j, Distribution of nonresponders calculated as the fold change of the cumulative percentage of nonresponders (negative values) for each of the indicated categories tested at Vax1–Vax3 (RBD-specific IgG, spike++ B cells and cTFH cells) and Vax2–Vax3 (WA.1 nAb). For boxplots in (b) and (c), dots represent individual samples tested; horizontal lines indicate the median. HCQ, hydroxychloroquine; AZA, azathioprine; MTX, methotrexate; MMF, mycophenolate mofetil; BLM, belimumab.
