The effect of adalimumab on key drivers in the pathogenesis of psoriasis

Abstract

Summary Background The use of recently introduced biologics targeting specific immune mechanisms has identified crucial steps in the pathogenesis of psoriasis. Studying the dynamics of changes of these target mechanisms in sequential skin biopsies during treatment with biologics may reveal potential biomarkers. Correlation between clinical parameters and the expression of specific genes during treatments may identify markers indicative of treatment response. Objectives This observational open‐label study aimed to provide an overview of important cell biological changes in lesional skin during treatment with adalimumab, and their relationship to clinical improvement. Methods Ten patients with moderate‐to‐severe plaque psoriasis were included and treated with adalimumab for 16 weeks. At baseline, and after 10 days and 16 weeks of treatment clinical scores were assessed and biopsies were taken to examine gene expression at the mRNA and protein level. Results The expression of marker genes for innate immunity, and epidermal differentiation and proliferation was rapidly restored to normal levels, whereas genes of the adaptive immune system showed a delayed decrease. The static and dynamic course of CD1a+ Langerhans cells and Ki67+ nuclei showed a significant strong correlation to the Psoriasis Area and Severity Index score. No correlation between interleukin‐17 expression and clinical scores was found. Conclusions The innate immune system is affected during adalimumab treatment well before the changes in the adaptive immune system become apparent. We may speculate that the addition of a treatment with an early effect on adaptive immunity to adalimumab may result in superior effectiveness compared with monotherapies.

Effects of adalimumab, etanercept and ustekinumab on the expression of psoriasin (S100A7) in psoriatic skin

“…In particular, S100A7 expression was decreased in adalimumab-treated patients compared to untreated-ones. Similar results were obtained by other authors, who have shown a decreased expression level of S100A7 mRNA [25,26]. In etanercept-treated specimens, the lack of a significant normalization of psoriasin levels is not consistent with a previous study, where, under similar conditions, such decrease achieved a significant value [27].…”

Perfusion Intensity Correlates with Expression Levels of Psoriasis-Related Genes and Proteins

“…An important exception is the mRNA expression level of TNF-α, showing no significant differences. These findings fit the results of previous studies that the TNF-α expression is regulated posttranscriptionally [29][30][31][32] . This indicates that there is a heterogenous cell biological composition within a clinically homogenous-appearing lesion as well as within the clinically unaffected skin, which is related to the perfusion intensity.…”

Landscape of Long Noncoding RNAs in Psoriatic and Healthy Skin

“…As TNF-α plays an important role in the inflammatory process and has been found in elevated levels in psoriasis patients, the targeting and inhibition of TNF-α has become a key approach to treating psoriasis. It has been shown that treatment with adalimumab causes a decrease in expression of various cytokines and transcription factors, eg., IL17, beta-defensins in psoriatic skin (Hendriks et al 2013). Our results indicated that lncRNA profile of post-treated skin was significantly different from pre-treated skin and was closer to normal skin.…”