Identification of RGS1 as a candidate biomarker for undifferentiated spondylarthritis by genome-wide expression profiling and real-time polymerase chain reaction.
OBJECTIVE
To compare gene expression profiles between ankylosing spondylitis (AS) and undifferentiated spondylarthritis (uSpA) patients with inflammatory low back pain.


METHODS
Peripheral blood mononuclear cells (PBMCs) from patients with AS, patients with uSpA, and healthy subjects were screened using genome-wide microarrays, followed by validation by real-time polymerase chain reaction (PCR).


RESULTS
Microarray profiling and real-time PCR assays showed only minor differences between AS patients and healthy subjects. In contrast, 20 genes were strikingly more highly expressed in uSpA patients. Regulator of G protein signaling 1 (RGS1) was identified as the most useful biomarker for distinguishing uSpA patients, and to a lesser extent AS patients, from control subjects (P = 2.3 x 10(-7) and 6.7 x 10(-3), respectively). These findings were verified in an independent cohort that also included patients with rheumatoid arthritis and patients with mechanical low back pain. The receiver operating characteristic area under the curve values in the first and second cohorts of uSpA patients were 0.99 and 0.93, respectively (P = 1 x 10(-4)). To evaluate the possible derivation of RGS1, we cultured a monocyte-derived cell line with a panel of cytokines and chemokines. RGS1 was significantly induced either by tumor necrosis factor alpha (TNFalpha) or by interleukin-17 (IL-17).


CONCLUSIONS
Our findings indicate that uSpA PBMCs carry strikingly more highly expressed genes compared with PBMCs from AS patients or healthy subjects, and that TNFalpha- and IL-17-inducible RGS1 is a potential biomarker for uSpA, and to a lesser extent for AS, with inflammatory low back pain.
Gu
Jieruo
J
Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Wei
Yu-Ling
YL
Wei
James C C
JC
Huang
Feng
F
Jan
Ming-Shiou
MS
Centola
Michael
M
Frank
Mark B
MB
Yu
David
D
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002478:Cells, Cultured; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020710:RGS Proteins / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025241:Spondylarthritis / Q000097:blood* / Q000175:diagnosis*; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000175:diagnosis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015415:Biomarkers; D020381:Interleukin-17; D020710:RGS Proteins; C080831:RGS1 protein, human; D014409:Tumor Necrosis Factor-alpha