iTRAQ-based proteomic identification of leucine-rich alpha-2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases.
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.
Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-asagi, Ibaragi, Osaka, Japan.
Satoshi
S
Serada
Minoru
M
Fujimoto
Atsushi
A
Ogata
Fumitaka
F
Terabe
Toru
T
Hirano
Hideki
H
Iijima
Shinichiro
S
Shinzaki
Teppei
T
Nishikawa
Tomoharu
T
Ohkawara
Kota
K
Iwahori
Nobuyuki
N
Ohguro
Tadamitsu
T
Kishimoto
Tetsuji
T
Naka
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000188:drug therapy; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000188:drug therapy; D001528:Behcet Syndrome / Q000175:diagnosis; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D003424:Crohn Disease / Q000175:diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D000069285:Infliximab; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D001798:Blood Proteins; D006023:Glycoproteins; C015246:LRG1 protein, human; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000069285:Infliximab