Cytokine responses in non-lesional psoriatic skin as clinical predictor to anti-TNF agents.

Aug 5, 2021

Contributor: Lam C Tsoi,Matthew T Patrick,Shao Shuai,Mrinal K Sarkar,Sunyi Chi,Bethany Ruffino,Allison C Billi,Xianying Xing,Ranjitha Uppala,Cheng Zang,Joseph Fullmer,Zhi He,Emanual Maverakis,Nehal N Mehta,Bethany E Perez White,Spiro Getsios,Yolanda Helfrich,John J Voorhees,J Michelle Kahlenberg,Stephan Weidinger,Johann E Gudjonsson

Cytokine responses in non-lesional psoriatic skin as clinical predictor to anti-TNF agents.

A major issue with the current management of psoriasis is our inability to predict treatment response.
Our aim was to evaluate the ability to use baseline molecular expression profiling to assess treatment outcome for psoriatic patients.
We conducted a longitudinal study of 46 patients with chronic plaque psoriasis treated with anti-TNF agent etanercept, and molecular profiles were assessed in over 200 RNA-seq samples.
We demonstrated correlation between clinical response and molecular changes during the course of the treatment, particularly for genes responding to IL-17A/TNF in keratinocytes. Intriguingly, baseline gene expressions in non-lesional, but not lesional skin, were the best marker of treatment response at week 12. We identified USP18, a known regulator of IFN responses, as positively correlated with PASI improvement (p=9.8×10) and demonstrate its role in regulating IFN/TNF responses in keratinocytes. Consistently, cytokine gene signatures enriched in baseline non-lesional skin expression profiles had strong correlations with PASI improvement. Using this information, we developed a statistical model for predicting PASI 75 (i.e. 75% of PASI improvement) at week 12, achieving AUC=0.75 and up to 80% accurate PASI75 prediction among the top predicted responders.
Our results illustrate feasibility of assessing drug response in psoriasis utilizing non-lesional skin and implicate involvement of IFN regulators in anti-TNF responses.

Copyright © 2021. Published by Elsevier Inc.

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About The Expert

Lam C Tsoi

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor MI, USA; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA. Electronic address: alextso@umich.edu.

Matthew T Patrick

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Shao Shuai

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi’an, Shannxi, China.

Mrinal K Sarkar

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Sunyi Chi

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.

Bethany Ruffino

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Allison C Billi

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Xianying Xing

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Ranjitha Uppala

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Cheng Zang

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Joseph Fullmer

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Zhi He

Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.

Emanual Maverakis

Department of Dermatology, School of Medicine, UC-Davis Medical Center, 2315 Stockton Blvd, Sacramento, CA, 95817, USA.

Nehal N Mehta

Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.

Bethany E Perez White

Department of Dermatology, Northwestern University, Chicago, IL 60611, USA.

Spiro Getsios

Department of Dermatology, Northwestern University, Chicago, IL 60611, USA.

Yolanda Helfrich

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

John J Voorhees

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

J Michelle Kahlenberg

Divison of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.

Stephan Weidinger

Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Johann E Gudjonsson

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: johanng@med.umich.edu.

References

PubMed