iTRAQ-based proteomic identification of leucine-rich alpha-2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases

Ann Rheum Dis. 2010 Apr;69(4):770-4. doi: 10.1136/ard.2009.118919. Epub 2009 Oct 22.

Abstract

Objective: To identify a novel serum biomarker of disease activity in inflammatory autoimmune disorders.

Methods: Sera obtained from rheumatoid arthritis (RA) patients before and after anti-TNF therapy were analysed by iTRAQ (isobaric tags for relative and absolute quantitation) quantitative proteomic analysis and further validated by ELISA.

Results: Of 326 proteins identified by proteomic analysis, increased serum levels of leucine-rich alpha-2 glycoprotein (LRG) was identified in RA patients before therapy. Serum LRG concentrations were significantly elevated in RA patients compared with healthy controls and decreased after anti-TNF therapy. Furthermore, serum LRG concentrations correlated with disease activity in RA and Crohn's disease (CD). Interestingly, in a subpopulation of patients with active CD and normal C-reactive protein levels, serum LRG concentrations were elevated.

Conclusions: LRG represents a novel serum biomarker for monitoring disease activity during therapy in autoimmune patients, particularly useful in patients with active disease but normal CRP levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / drug therapy
  • Autoimmune Diseases / diagnosis*
  • Autoimmune Diseases / drug therapy
  • Behcet Syndrome / diagnosis
  • Biomarkers / blood
  • Blood Proteins / metabolism
  • C-Reactive Protein / metabolism
  • Crohn Disease / diagnosis
  • Enzyme-Linked Immunosorbent Assay
  • Glycoproteins / blood*
  • Humans
  • Infliximab
  • Proteomics / methods
  • Reproducibility of Results
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Biomarkers
  • Blood Proteins
  • Glycoproteins
  • LRG1 protein, human
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Infliximab