Protein biomarker analysis by mass spectrometry in patients with rheumatoid arthritis receiving anti-tumor necrosis factor-alpha antibody therapy.
OBJECTIVE
To investigate the mechanism of action of anti-tumor necrosis factor-alpha (TNF-alpha) antibody in patients with rheumatoid arthritis (RA), we analyzed serum or plasma proteins by mass spectrometry system.


METHODS
Ten RA patients who received treatment with anti-TNF-alpha antibody were studied. Samples obtained before and after therapy were analyzed by a two-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS) system after pretreatment by a recently developed method to remove high molecular weight proteins.


RESULTS
Using this system, certain proteins were identified after treatment with anti-TNF-alpha antibody, including proteins related to the TNF-alpha-mediated pathway for nuclear factor kappa B (NF-kappaB) activation and/or to the metabolism (including regeneration) of articular cartilage.


CONCLUSIONS
Our mass spectrometry system appears to be useful for proteomic analysis. The efficacy of anti-TNF-alpha antibody therapy for RA may be related to various consequence of the inhibition of TNF-alpha activity.
Department of Internal Medicine, Juntendo University Urayasu Hospital, Chiba, Japan. sekigawa@juntendo-urayasu.jp
I
I
Sekigawa
M
M
Yanagida
K
K
Iwabuchi
K
K
Kaneda
H
H
Kaneko
Y
Y
Takasaki
G
G
Jung
S
S
Sone
Y
Y
Tanaka
H
H
Ogawa
K
K
Takamori
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002853:Chromatography, Liquid; D055513:Connective Tissue Growth Factor; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D000069285:Infliximab; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D055513:Connective Tissue Growth Factor; D000069285:Infliximab