Persistence of inflammatory phenotype in residual psoriatic plaques in patients on effective biologic therapy: Residual Psoriatic Plaques After Treatment.

Many psoriasis patients treated with biologics do not achieve total skin clearance. These patients possess "residual plaques" despite ongoing biologic treatment. To elucidate mechanisms of plaque persistence despite overall good drug response, we studied fifty subjects: psoriasis patients with residual plaques treated with one of three different biologics, untreated patients, and healthy controls. Skin biopsies from all subjects were characterized using three methods: mRNA expression, histology, and FACS of skin hematopoietic cells. While all three methods provided evidence of drug effect, gene expression analysis revealed persistence of key psoriasis pathways in treated plaques including "Granulocyte Adhesion and Diapedesis", "Th17 Activation Pathway", and "Interferon Signaling" with no novel pathways emerging. Focal decreases in parakeratosis and keratinocyte proliferation and differential reduction in IL-17 producing CD103 T cells but no change in CD103 TRM T cells were observed. Of note anti-TNF increased "Interferon Signaling" pathway already present. Interestingly mast cells were the dominant source of IL-22 in all psoriasis subjects. These data suggest that while subtle differences can be observed in drug treated plaques, underlying biological mechanisms are similar to those present in untreated psoriatic lesions.