Objective: To identify a novel serum biomarker of disease activity in inflammatory autoimmune disorders using a quantitative proteomic approach.
Methods: Sera obtained from rheumatoid arthritis (RA) patients before and after anti-TNF therapy were analyzed by quantitative proteomics using isobaric tags for relative and absolute quantitation (iTRAQ) and further validated by ELISA.
Results: Of 326 proteins identified by proteomic analysis, we identified increased serum levels of leucine rich alpha 2 glycoprotein (LRG) in RA patients before therapy. ELISA analysis revealed that serum LRG concentrations were significantly elevated in RA patients compared to healthy controls and decreased after anti-TNF therapy. Serum LRG concentrations correlated with serum C-reactive protein (CRP) levels in patients with RA, Behcet’s disease and Crohn’s disease (CD) and correlated with disease activity in RA and CD. Interestingly, in a subpopulation of active CD patients with normal CRP levels, serum LRG concentrations were elevated. Furthermore, serum LRG concentrations were significantly higher in CD patients refractory to anti-TNF therapy compared to those responsive to this therapy.
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. Therefore, serum LRG potentially surrogate for CRP.