The effects of infliximab therapy on the serum proteome of rheumatoid arthritis patients.
BACKGROUND
Although the clinical effects of infliximab therapy in rheumatoid arthritis have been documented extensively, the biological effects of this intervention continue to be defined. We sought to examine the impact of infliximab therapy on the serum proteome of rheumatoid arthritis patients by means of a mass spectrometry-based approach.


METHODS
Sera from 10 patients with rheumatoid arthritis were obtained prior to and following 12 weeks of infliximab therapy using a standard clinical protocol. The sera were immunodepleted of the 12 highest abundance proteins, labeled by the iTRAQ (isobaric tagging for relative and absolute protein quantification) technique, and analyzed by mass spectrometry to identify proteomic changes associated with treatment.


RESULTS
An average of 373 distinct proteins were identified per patient with greater than 95% confidence. In the 3 patients demonstrating the most robust clinical responses, changes of greater than 20% in the serum levels were observed in 39 proteins following treatment. The majority of these proteins were regulated directly or indirectly by tumour necrosis factor-alpha (TNF-alpha) and nuclear factor-kappa-B, with acute-phase proteins being uniformly down-regulated. A number of proteins, including members of the SERPIN family and S100A8, were down-regulated irrespective of clinical response.


CONCLUSIONS
The present study demonstrates that a robust clinical response to infliximab is associated with the down-regulation of a spectrum of serum proteins regulated by TNF-alpha, and provides a possible basis for defining the broader biological effects of the treatment in vivo.
Dwivedi
Ravi C
RC
Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, MB, Canada. dwivedi@cc.umanitoba.ca
Dhindsa
Navjot
N
Krokhin
Oleg V
OV
Cortens
John
J
Wilkins
John A
JA
El-Gabalawy
Hani S
HS
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D000069285:Infliximab; D008875:Middle Aged; D020543:Proteome / Q000187:drug effects*; D021241:Spectrometry, Mass, Electrospray Ionization
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D020543:Proteome; D000069285:Infliximab