Fig. 3

A defective ICs’ clearance due to complement alteration and increased apoptosis (i.e., UV light induced) lead to the formation of IC consisting of self-DNA/RNA rich in CpG motifs, hypomethylated, oxidized. These ICs may bind other molecules such as HMGB1 (released from dead cells) or the antimicrobial peptide LL37-forming structures capable of inducing pDCs’ activation through different pathways (i.e., RAGE, FcγRIIA and/or TLRs). Of note in SLE patients, IFN-α activity is increased, since IFN-alfa genetic signature can be detecting in circulating monocytes using a microarray technique. (ICs immune complexes, FcγRIIA low affinity receptor for IgG, BCR B cell receptor, HMGB1 high mobility group box 1, RAGE receptor for advanced glycation end products, LL37 antimicrobial peptide or cathelicidin)