Therapeutic drug monitoring of patients with psoriasis during tumour necrosis factor (TNF)-α antagonist treatment using a novel interleukin-8 reporter cell line

Y. Kimura, R. Shimada-Omori, T. Takahashi, K. Tsuchiyama, Y. Kusakari, K. Yamasaki, R. Nishikawa, C. Nishigori, S. Aiba

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Background: Tumour necrosis factor (TNF)-α antagonist therapy is currently used for moderate and severe psoriasis. However, this treatment has several drawbacks, including interindividual variability in clinical response and secondary loss of effectiveness. Objectives: To evaluate quantitatively the TNF-α-neutralizing activity of the plasma of patients with psoriasis during TNF-α antagonist therapy and to determine poor responders objectively. Methods: We used a human interleukin-8 reporter monocyte cell line, THP-G8, that harbours a stable luciferase orange (SLO) gene under the control of the interleukin-8 promoter. After confirming its dose-dependent response to exogenous TNF-α, we examined the suppressive activity of TNF-α antagonists and of the patients’ plasma during TNF-α antagonist therapy on TNF-α-induced SLO luciferase activity (TNF-SLO-LA). Results: Pretreatment of TNF-α with TNF-α antagonists or with the plasma of patients with psoriasis who achieved 75% improvement in Psoriasis Area and Severity Index (PASI 75) dose dependently suppressed TNF-SLO-LA. There was a significant correlation between change in PASI and percentage suppression (inhibitory rate of a 1 : 2 dilution of patient plasma on TNF-SLO-LA). A percentage suppression of 50·3% has a positive predictive value of 87% of achieving PASI 75, with a sensitivity of 93% and a specificity of 80%. Conclusions: Therapeutic monitoring of patients with psoriasis during TNF-α antagonist therapy using THP-G8 can provide a useful tool to determine objectively the efficacy of the administered TNF-α antagonists.

Original languageEnglish
Pages (from-to)979-987
Number of pages9
JournalBritish Journal of Dermatology
Volume175
Issue number5
DOIs
Publication statusPublished - 2016

ASJC Scopus subject areas

  • Dermatology

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