From gene expression to serum proteins: biomarker discovery in ankylosing spondylitis.
OBJECTIVE
Studying post-infliximab gene expression changes could provide insights into the pathogenesis of ankylosing spondylitis (AS).


METHODS
Gene expression changes were screened by microarray on peripheral blood RNA of 16 AS patients at baseline and 2 weeks post-infliximab, and selected results were confirmed by quantitative real-time (qRT)-PCR. Corresponding serum-soluble LIGHT (sLIGHT) was estimated by ELISA and the fold change in sLIGHT was correlated to the fold change in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and the Bath AS disease activity index.


RESULTS
Post-infliximab, 69% of the patients (11/16) achieved an ASAS20 response. Six candidate genes were differentially expressed by microarray; four of which were validated by qRT-PCR. sLIGHT showed the most significant difference. There was good correlation of baseline sLIGHT with CRP (R = 0.60; p = 0.01) and ESR (R = 0.51; p = 0.04). The fold change in sLIGHT correlated with change in both CRP (R = 0.71, p = 0.002) and ESR (R = 0.77, p<0.001).


CONCLUSIONS
LIGHT is significantly downregulated by infliximab. sLIGHT correlated well with changes in inflammatory markers.
Haroon
N
N
Toronto Western Hospital, Toronto, ON M5T 2S8, Canada.
Tsui
F W L
FW
O'Shea
F D
FD
Chiu
B
B
Tsui
H W
HW
Zhang
H
H
Marshall
K W
KW
Inman
R D
RD
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000188:drug therapy*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000097:blood; D055815:Young Adult
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D001798:Blood Proteins; C505914:TNFSF14 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D002097:C-Reactive Protein; D000069285:Infliximab