(A) Volcano plots show changes in specific circRNA and mRNA expression in lesional psoriasis skin before treatment (L D0; left) and during secukinumab treatment on day 42 (middle) and 84 (right). Plots depict adjusted (adj.) p-values relative to log2FC. Multiple paired t-test with correction for multiple comparisons (FDR-Benjamini-Hochberg); n(NL, L D4, L D14, and L D43) = 14, n(L D0) = 13, and n(L D84) = 12. Black points depict circRNAs with a |log2FC| > 1 and adj.-p-value < 0.05. Orange points depict mRNAs (FUS, HNRNPL, DHX9, ADAR, and QKI). (B) Hematoxylin staining combined with RNA CISH for ciRS-7 during treatment with secukinumab. Paired biopsies from non-lesional and lesional skin before (L D0), and 4, 14, 42, and 84 days after treatment initiation. Four micrometer sections of paraffin-embedded biopsies with one representative patient shown. Scale bar: 100 μm and 25 μm in zoom-in. (C) Boxplot showing the median log2FC of individual circRNAs in lesional D84 relative to D0 skin dependent on whether or not they characterize as Alu-mediated circRNA (presence of IAEs within 2300 nucleotide regions flanking the BSJs). Twenty circRNAs out of 48 circRNAs were considered Alu-mediated. Depicted are median values with whiskers extending to min. and max. values. Two-tailed Mann-Whitney test; n = 11. BSJ = backsplicing junction; CISH = chromogenic in situ hybridization; IAE = Inverted Alu elements.