Serum proteome analysis in patients with rheumatoid arthritis receiving therapy with etanercept, a chimeric tumor necrosis factor-alpha receptor.
OBJECTIVE
Rheumatoid arthritis (RA) is a chronic inflammatory disorder of the synovium resulting in the destruction of affected joint cartilage and bone structures. Etanercept is a biological agent that blocks the tumor necrosis factor-α (TNF-α)-mediated inflammatory processes in RA patients, and has a regenerative effect on cartilage. In order to identify novel disease-related proteins and candidate biomarkers, we performed proteomic profiling of the serum in patients with RA who were treated with etanercept.


METHODS
Serum samples were obtained from eight RA patients before and after etanercept treatment. The low molecular weight proteins in the serum were concentrated and analyzed by liquid chromatography-tandem mass spectrometry. The results before and after etanercept treatment were compared by the spectrum count method.


RESULTS
Among a total of 477 proteins identified, 12 were found to be decreased and five were increased by etanercept treatment. Some of the changed proteins were known to be related to RA, and most of the other changed proteins may play possible roles in the TNF-α signaling pathway or the state of cartilage and extracellular matrix.


CONCLUSIONS
The present proteomic study identified several proteins that could be involved in the pathogenesis of RA. These findings could thus lead to the identification of novel candidate disease-related protein biomarkers for RA, or indicate new targets for therapy.
Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, and Department of Internal Medicine, Juntendo University Urayasu Hospital, Chiba, Japan. yanagida@juntendo.ac.jp
Mitsuaki
M
Yanagida
Giman
G
Jung
Yoshinori
Y
Tanaka
Saburo
S
Sone
Maki
M
Fujishiro
Keigo
K
Ikeda
Kazuhisa
K
Nozawa
Hiroshi
H
Kaneko
Yoshinari
Y
Takasaki
Hideoki
H
Ogawa
Kenji
K
Takamori
Iwao
I
Sekigawa
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy*; D011416:Complement Factor D / Q000378:metabolism; D004745:Enkephalins / Q000097:blood; D000068800:Etanercept; D016326:Extracellular Matrix Proteins / Q000097:blood; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D019746:Intramolecular Oxidoreductases / Q000097:blood; D007704:Kininogens / Q000097:blood; D054834:Lipocalins / Q000097:blood; D008875:Middle Aged; D011498:Protein Precursors / Q000097:blood; D011509:Proteoglycans / Q000097:blood; D020543:Proteome / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D000099158:Proteoglycan 4
D011416:Complement Factor D; D004745:Enkephalins; D000068800:Etanercept; D016326:Extracellular Matrix Proteins; D007074:Immunoglobulin G; D019746:Intramolecular Oxidoreductases; D007704:Kininogens; D054834:Lipocalins; D011498:Protein Precursors; D011509:Proteoglycans; D020543:Proteome; D018124:Receptors, Tumor Necrosis Factor; C492373:FBLN5 protein, human; C419197:PRG4 protein, human; D000099158:Proteoglycan 4; C029992:proenkephalin; C022466:prostaglandin R2 D-isomerase