Biomarkers for methotrexate-induced liver injury: urinary protein profiling of psoriasis patients

Rachel P L van Swelm, Coby M M Laarakkers, Marisol Kooijmans-Otero, Elke M G J de Jong, R. Masereeuw, Frans G M Russel

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Hepatic fibrosis is an adverse drug reaction of methotrexate (MTX) seen after long-term use in psoriasis patients. Currently, patients are monitored for MTX-induced hepatic fibrosis by performing liver biopsy, which is risky and burdensome for the patient, or by measuring plasma procollagen type III aminopeptide (PIIINP), which is not conclusive. The objective of this study was to identify novel predictive and preferably non-invasive biomarkers to monitor psoriasis patients for MTX-induced hepatic fibrosis. Urine samples were collected from 60 psoriasis patients treated with MTX and divided into two categories: low cumulative dose (< 1500 mg MTX) and high cumulative dose (> 1500 mg). Urinary proteins were profiled using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and identified using electrospray ionization LTQ. In urine of psoriasis patients with high cumulative MTX dose multiple proteins were identified that are associated with hepatic fibrosis, such as N-cadherin, inter-alpha-trypsin inhibitor heavy chain H4, haptoglobin and serotransferrin. These proteins may be candidate urinary biomarkers to monitor MTX-induced hepatic fibrosis. In conclusion, urinary proteome analysis identified a profile of potentially predictive biomarkers for MTX-induced hepatic fibrosis in psoriasis patients with high cumulative dose of MTX.

Original languageEnglish
Pages (from-to)219-24
Number of pages6
JournalToxicology Letters
Volume221
Issue number3
DOIs
Publication statusPublished - 29 Aug 2013

Bibliographical note

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Keywords

  • Adolescent
  • Adult
  • Aged
  • Biological Markers
  • Drug-Induced Liver Injury
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Liver Cirrhosis
  • Male
  • Methotrexate
  • Middle Aged
  • Proteomics
  • Psoriasis
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Statistics, Nonparametric
  • Young Adult

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