Figure 7. Anti-Ro52 antibody subsets are associated with distinct transcriptional immune-mediated pathways in SLE.
(A and B) Three-way differentially expressed transcript (DET) analysis between patients with SLE positive for anti-Ro52Ex4 (n = 95), anti-Ro52Nt (n = 9), and anti-Ro52γCT (n = 21) antibodies. DET between the 3 anti-Ro52 antibody types (n = 926) are shown in a 3D volcano plot (A) and in a radial plot (B). Significance was calculated using the volcano3D package by combining the results of the F test and pairwise comparisons between anti-Ro52Ex4, anti-Ro52Nt, and anti-Ro52γCT, using a multivariate linear model adjusted by anti-DNA positivity and SLEDAI. Color code denotes significant DET in anti-Ro52Ex4 (red), anti-Ro52γCT (green), anti-Ro52Nt (blue), and overlapping genes between anti-Ro52Ex4 and anti-Ro52γCT (yellow), anti-Ro52Nt and anti-Ro52Ex4 (purple), and anti-Ro52γCT and anti-Ro52Nt (light blue). Representative genes from the enriched pathways on each DET subset are labeled. (C) Activity of the IFN pathway in patients negative for anti-Ro52 (n = 63) and patients with SLE positive for anti-Ro52Ex4 (n = 95), anti-Ro52Nt (n = 9), and anti-Ro52γCT (n = 21) antibodies. Pathway activity was calculated using gene set variation (GSVA) score. Comparisons between groups were done using the pairwise Wilcoxon test. *P < 0.05, ****P < 0.0001.