Role of IL-1ra and Granzyme B as biomarkers in active Crohn's disease patients

Biomarkers. 2018 Mar;23(2):161-166. doi: 10.1080/1354750X.2017.1387933. Epub 2017 Oct 16.

Abstract

Background and aim: Altered gene expression in intestinal mucosa is thought to contribute to inflammatory process in Crohn's disease (CD). The present study investigated changes in the expression of genes associated with gut inflammation in CD patients by RNA microarray to identify disease biomarkers.

Methods: Microarray analysis was carried out in formalin-fixed, paraffin-embedded intestinal tissue specimens from six CD patients who underwent surgery without prior treatment and from two healthy control subjects. Transcripts overexpressed in CD patients were validated by enzyme-linked immunosorbent assay (ELISA) using specimens from 46 CD patients and 60 healthy controls.

Results: Among the genes over-expressed with statistical significance, five genes including decay-accelerating factor, interleukin-1 receptor (IL1R) A, tumour necrosis factor receptor 2, (C-X-C motif) ligand (CXCL) 1, and granzyme (GZM) B proposed to have functional association with CD were selected to validate the expressed transcripts in serum. Serum concentration of IL1RA, CXCL1, and GZMB measured by ELISA were significantly higher in CD patients.

Conclusions: We identified that IL1RA, CXCL1, and GZMB are overexpressed in CD patients. Serum IL1RA and GZMB levels were markedly increased in CD patients, suggesting that these markers can serve as biomarkers to identify gut inflammation. Further studies will be required to evaluate this possibility.

Keywords: Crohn’s disease; RNA microarray; biomarker; inflammatory bowel disease; transcripts.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biomarkers / metabolism*
  • Chemokine CXCL1 / genetics
  • Chemokine CXCL1 / metabolism
  • Crohn Disease / blood
  • Crohn Disease / diagnosis
  • Crohn Disease / genetics*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Profiling*
  • Granzymes / blood
  • Granzymes / genetics*
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Interleukin 1 Receptor Antagonist Protein / blood
  • Interleukin 1 Receptor Antagonist Protein / genetics*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis / methods
  • ROC Curve
  • Young Adult

Substances

  • Biomarkers
  • CXCL1 protein, human
  • Chemokine CXCL1
  • Interleukin 1 Receptor Antagonist Protein
  • GZMB protein, human
  • Granzymes