Increased tumor necrosis factor-alpha mRNA expression in whole blood from patients with rheumatoid arthritis: reduction after infliximab treatment does not predict response.
OBJECTIVE
It has been suggested that patients with rheumatoid arthritis (RA) with abundant tumor necrosis factor-alpha (TNF-alpha) are more likely to respond to TNF-alpha inhibitors. We measured expression of TNF-alpha mRNA in peripheral blood of RA patients undergoing infliximab treatment in order to test its predictive value for treatment response.


METHODS
Forty-four RA patients showing persistent disease activity and 27 healthy controls were studied. Peripheral blood TNF-alpha mRNA levels were measured before and 4 hours after the first infliximab infusion and at Week 22 using quantitative RT-PCR. Results were correlated to the treatment response at Week 22 in the whole RA cohort and a subset of patients showing high TNF-alpha mRNA levels at baseline.


RESULTS
At baseline and at Week 22, TNF-alpha mRNA expression in RA patients was significantly increased compared to healthy controls. At both timepoints, no significant difference was observed between responders and nonresponders. Compared to baseline, infliximab treatment induced a decrease in TNF-alpha mRNA level at 4 hours and at Week 22, although this effect was significant only in patients with high TNF-alpha mRNA expression at baseline. Such variation compared to baseline was similar in responders and nonresponders.


CONCLUSIONS
Peripheral blood TNF-alpha mRNA expression is increased in RA, but its reduction with anti-TNF treatment is not associated with treatment response.
Pachot
Alexandre
A
Joint Unit, Hospices Civils de Lyon-bioMérieux, Hôpital Edouard Herriot, Hôpital Edouard Herriot, 5 place d'Arsonval, Lyon, France.
Arnaud
Béatrice
B
Marrote
Hubert
H
Cazalis
Marie-Angélique
MA
Diasparra
Jennifer
J
Gouraud
Aurore
A
Mougin
Bruno
B
Miossec
Pierre
P
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics*
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab