PracticeUpdate Conference Series: IID 2018

" …the results provided insight into molecular transformation during anti-interleukin 17A treatment. They provide an explanation of the molecular “scar” that is generated when psoriasis is in remission. "

Molecular transformation during interleukin 17A treatment T rine Bertelsen, MD, of Aarhus University in Denmark, explained that antagonists of inter- leukin 17 have proven to be highly effective for psoriasis. Many mechanisms underlying this efficacy, however, have yet to be determined. Moreover, mechanisms underlying molecular remission of psoriasis remain elusive. Dr. Bertelsen and colleagues set out to investigate molecular complexity in psoriatic patients during treatment with an anti-interleukin 17A agent. Fourteen patients treated with secukinumab (anti-in- terleukin 17A) were included. Skin biopsies and blood samples were collected at day 0, 4, 14, 42, and 84. Clinical scores such as Psoriasis Affected Surface Area, Physician's Global Assessment, and body surface area were registered at each visit. Samples were then processed for microar- ray, quantitative polymerase chain reaction, and immunohistochemistry. Inflammatory mediators such as CXCL8, interleukin 19, DEFB4, and interleukin 36A were downregu- lated early, at day 4 after the start of treatment. Other mediators such as S100A7, interleukin 20, and CCL20 were downregulated at day 14. Moreover, when comparing nonlesional skin with previous lesional skin at day 84, expression of sev- eral molecular markers was altered, even though psoriasis had cleared.

IкBζ, encoded by the NFKBIZ gene, is a key reg- ulator in psoriasis through its role in mediating interleukin 17A-driven effects. Interestingly, NFKBIZ mRNA expression was downregulated during anti-interleukin 17A treatment and correlated with clinical scores. Therefore, signaling pathways involved in interleu- kin 17A-induced IкBζ expression were investigated further in human keratinocytes. By using siRNA knockdown and quantitative polymerase chain reaction, Dr. Bertelsen’s team demonstrated IкBζ to be mediated through an Act1/p38 MAPK/c-Jun/ NF-кB- dependent mechanism. Dr. Bertelsen concluded that the results provided insight into molecular transformation during anti-interleukin 17A treatment. They provide an explanation of the molecular “scar” that is gener- ated when psoriasis is in remission. Furthermore, the results presented IкBζ as an important player in interleukin 17A-driven effects in psoriasis.

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IID 2018 • PRACTICEUPDATE CONFERENCE SERIES 11