Abstract
Psoriasis is a T-cell mediated disease that involves IL-23/Th17 and IL-12/Th1 axes. Ustekinumab, a fully human monoclonal antibody targeting the p40 subunit of both IL-12 and IL-23, has proven to be efficient and safe for treating patients with psoriasis. Yet, there have been no reports with human skin/blood samples that would elucidate the molecular mechanisms by which ustekinumab calms psoriasis skin lesions. To investigate the efficacy and molecular pathway (RORC, t-BOX and GATA) of ustekinumab in treating patients with psoriasis skin lesions. A total of 30 patients with psoriasis were randomized into placebo group and treatment group. PASI of each patient was calculated at 0, 12 and 24 weeks post-treatment. The mRNA levels of RORC, t-BOX and GATA in peripheral blood mononuclear cells separated from patients’ whole blood were analyzed using qPCR. Decreased mRNA of RORC, t-BOX and GATA were observed after continuous injections, indicating that ustekinumab exerts its effect by interacting with these molecules; while no significant difference in foxp3 mRNA levels were found between placebo group and treatment group.
Highlights
Psoriasis is a chronic, inflammatory and proliferative skin disease, characterized by impaired differentiation, overactive hyperproliferation of epidermal keratinocytes, disturbed keratinization and aberrant activation of T lymphocytes
Our aim was to verify our assumption that ustekinumab has longer sustainment because it can interact with RORC, T-box, foxp3 and GATA
PASI was adopted for the efficacy assessment; when PASI improvement rate reached or exceeded 75% (PASI-75), the treatment was considered effective
Summary
Inflammatory and proliferative skin disease, characterized by impaired differentiation, overactive hyperproliferation of epidermal keratinocytes, disturbed keratinization and aberrant activation of T lymphocytes. It involves complicated pro-inflammatory cytokine networks, where Th1/Th2 homeostasis, Th17/ Treg balance, IL-23/Th17 axis and IL-12/Th1 axis have shown to have important roles (Deng, Chang, Lu, 2016; Harden, Krueger, Bowcock, 2015). Ustekinumab stimulates peripheral blood monocytes (PBMC) so as to modulate cytokines (Nograles et al, 2008; Reddy et al, 2010). To our knowledge, there have been no reports with human skin/blood samples elucidating the pathway by which ustekinumab modulates full blood white cells influencing human keratinocytes’ cellular processes. There are no reports on how ustekinumab achieves its efficacy in the treatment of psoriasis and/or presents distinctive properties from other biologic agents
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