Serum microRNA levels in patients with Crohn's disease during induction therapy by infliximab.
OBJECTIVE
microRNAs (miRNAs) have been suggested to be candidates for biomarkers in various diseases including Crohn's disease (CD). To identify possible biomarkers predictive of the therapeutic effect of infliximab in CD, we investigated serum miRNA levels during the induction therapy by the medication.


METHODS
Nineteen CD patients who were applied to the induction therapy by infliximab were enrolled. Serum samples for miRNA analyses were obtained at weeks 0 and 6, and the therapeutic efficacy by infliximab was assessed according to the Crohn's disease activity index value at week 14. Exploratory miRNA profiling by low-density array was initially performed in three patients. The levels of candidate miRNA were subsequently determined by real-time polymerase chain reaction (PCR) assays in the remaining 16 patients. The miRNA levels during the induction therapy were compared between the two groups classified by the clinical response to infliximab at week 14.


RESULTS
Low-density array analysis identified 14 miRNAs that showed twofold or more altered expression during the induction therapy by infliximab. Subsequent analysis by real-time PCR demonstrated significantly increased levels of five miRNAs (let-7d, let-7e, miR-28-5p, miR-221, and miR-224) at week 6 when compared with those at week 0 (P < 0.05 each). In addition, miRNA levels of let-7d and let-7e were significantly increased in the group of patients who achieved clinical remission by infliximab (P = 0.001 and P = 0.002, respectively).


CONCLUSIONS
let-7d and let-7e might be possible therapeutic biomarkers in patients with CD, who are treated by infliximab.
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Shin
S
Fujioka
Ikuo
I
Nakamichi
Motohiro
M
Esaki
Kouichi
K
Asano
Takayuki
T
Matsumoto
Takanari
T
Kitazono
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D003424:Crohn Disease / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D035683:MicroRNAs; D000069285:Infliximab
Crohn's disease; infliximab; microRNAs