Persistence of Inflammatory Phenotype in Residual Psoriatic Plaques in Patients on Effective Biologic Therapy

Abstract

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 50 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 hematopoietic skin cells. Although all three methods provided evidence of drug effect, gene expression analysis revealed the persistence of key psoriasis pathways in treated plaques, including granulocyte adhesion and diapedesis, T helper type17 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 e T cells, but no change in CD103 þ tissue-resident memory T cells were observed. Of note, antitumor necrosis factor increased the 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 biologic mechanisms are similar to those present in untreated psoriatic lesions.

Paradoxical lichen planus induced during anti‐IL‐17A treatment is immunologically different from spontaneously occurring lichen planus

“…6,7 In agreement with other reports, the secukinumab-resistant PSO plaque showed a high expression of IL-17A. 8,9 The patient's paradoxical LP lesion did not show any IL-17A expression. Interestingly, the secukinumab-resistant PSO plaque showed some IL-4 expression, a cytokine, which is normally absent in PSO lesions.…”

“…8,9 Such elevated cytokine levels have been attributed to the persistence of CD3 + T cells, innate lymphoid cells and mast cells. 8,9 Although our findings are based on a single case study, they indicate some distinct immunological features of paradoxical LP and treatment-resistant PSO skin under anti-IL-17A blockade compared with spontaneous LP and untreated PSO skin. However, clinical presentation and histological features were similar within each skin disorder (Fig.…”

“…IL17, IL22 and IL23A) remained at elevated levels in treatment-resistant PSO skin. 8,9 Such elevated cytokine levels have been attributed to the persistence of CD3 + T cells, innate lymphoid cells and mast cells. 8,9 Although our findings are based on a single case study, they indicate some distinct immunological features of paradoxical LP and treatment-resistant PSO skin under anti-IL-17A blockade compared with spontaneous LP and untreated PSO skin.…”

Skin-Resident Memory T Cells: Pathogenesis and Implication for the Treatment of Psoriasis

“…Another study on residual psoriasis after the use of biologics revealed a decrease in keratinocyte proliferation. However, the percentage of IL-17A-producing CD103 + TRM was not significantly reduced after the treatments [92]. Similarly, a new normal in the persistence of IL-17A-producing TRM with CCR6 and IL-23R expression in the resolved skin has been established [62,80].…”

Tissue-Resident Memory T Cells in Skin Diseases: A Systematic Review

“…Furthermore, CD8 + T cells producing IL-17 and CD4 + T cells producing IL-22 remain in resolved lesions and can be stimulated to produce psoriasis-related cytokines even after treatment with biologics such as infliximab for several years [51]. Interestingly, the effect on the presence of TRMs of treatment with different biological drugs has also been studied and, so far, no difference in the number of CD103 + cells in residual psoriatic plaques has been shown [116]. The presence of IL-17A-producing CD8 + CD103 + TRMs in the epidermis has been found to contribute to the prognosis of psoriasis [52].…”